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1. Reintroducing photosynthesis.

Author: Vila F and Sanz A
Subjects: Educational Measurement, Humans, Biology education, Curriculum, Photosynthesis, Plant Physiological Phenomena
Abstract: This article reports on conceptual difficulties related to photosynthesis and respiratory metabolism of a Plant Physiology course for undergraduate students that could hinder their better learning of metabolic processes. A survey of results obtained in this area during the last 10 academic years was performed, as well as a specific test, aimed to find out prior conceptual schemes in the students. The test included only basic, general questions on plant metabolism, and was passed on the first day of the course. Scores obtained by different groups of students were compared. Survey of students' performance in previous years shows that questions on plant metabolism result in significantly lower number of correct answers than for the rest of questions, despite reiteration of its teaching in prior educational levels. Some areas such as respiration or light-independent reactions of photosynthesis, as well as concepts and terminology related to electrochemistry, seem to be particularly difficult. The specific test also shows differences among the different groups of students included in this investigation. Our results point out that reiteration of a particular subject in the curricula at different educational levels does not result in a coherent enough conceptual scheme in the students. To help students in this task, it is recommended to teach the general processes also in advanced courses in which these processes are taught in great detail. In this way, settlement of the appropriate conceptual scheme may be reinforced., (Copyright © 2012 Wiley Periodicals, Inc.)
Published: 2012
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2. Using Mini-Reports to Teach Scientific Writing to Biology Students

Author: Simmons, Alexandria D., Larios-Sanz, Maia, and Amin, Shivas
Abstract: Anyone who has taught an introductory biology lab has sat at their desk in front of a towering stack of lengthy lab reports and wondered if there was a better way to teach scientific writing. We propose the use of a one-page format that we have called a "mini-report," which we believe better allows students to understand the structure and characteristics of proper scientific writing and reduces the grading-time investment for instructors.
Published: 2014
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3. Mathematical Literacy in Plant Physiology Undergraduates: Results of Interventions Aimed at Improving Students' Performance

Author: Vila, Francisca and Sanz, Amparo
Abstract: The importance of mathematical literacy in any scientific career is widely recognized. However, various studies report lack of numeracy and mathematical literacy in students from various countries. In the present work, we present a detailed study of the mathematical literacy of Spanish undergraduate students of Biology enrolled in a Plant Physiology course. We have performed individual analyses of results obtained during the period 2000-2011, for questions in the examinations requiring and not requiring mathematical skills. Additionally, we present the outcome of two interventions introduced with the aim of helping students improve their prospects for success in the course. Our results confirm previous research showing students' deficiencies in mathematical skills. However, the scores obtained for mathematical questions in the examinations are good predictors of the final grades attained in Plant Physiology, as there are strong correlations at the individual level between results for questions requiring and not requiring mathematical skills. The introduction of a laboratory session devoted to strengthening the application of students' previously acquired mathematical knowledge did not change significantly the results obtained for mathematical questions. Since mathematical abilities of students entering university have declined in recent years, this intervention may have helped to maintain students' performance to a level comparable to that of previous years. The outcome of self-assessment online tests indicates that although Mathematics anxiety is lower than during examinations, the poor results obtained for questions requiring mathematical skills are, at least in part, due to a lack of self-efficacy.
Published: 2013
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4. Waldenström’s Macroglobulinemia: An Exploration into the Pathology and Diagnosis of a Complex B-Cell Malignancy

Author: Askari E, Rodriguez S, and Garcia-Sanz R
Subjects: waldenström’s macroglobulinemia, igm-mgus, pathology, biology, diagnosis, prognosis, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Elham Askari,1 Sara Rodriguez,2 Ramon Garcia-Sanz3 1Hematology Department, Fundación Jiménez Díaz, Centro de Investigación Biomédica en Red-Cáncer (CIBERONC) CB16/12/00369, Madrid, Spain; 2Clinica Universidad de Navarra, Centro de Investigación Medica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Accelerator project, Centro de Investigación Biomédica en Red-Cáncer (CIBERONC) CB16/12/00369, Pamplona, Spain; 3Haematology Department, University Hospital of Salamanca, Research Biomedical Institute of Salamanca (IBSAL), Accelerator project, Centro de Investigación Biomédica en Red-Cáncer (CIBERONC) CB16/12/00369 and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca, SpainCorrespondence: Ramon Garcia-SanzDepartment of Hematology, University Hospital of Salamanca, Paseo de San Vicente, 58-182, Salamanca, 37007, SpainTel +34 923291100Fax +34 923294624Email rgarcias@usal.esAbstract: After 77 years since the initial description, Waldenström macroglobulinemia (WM) remains as a bone marrow neoplastic disorder with lymphoplasmacytic differentiation oversecreting a monoclonal immunoglobulin M (IgM). However, many biological and genetic aspects of this entity have been unraveled and it is now easy to correctly diagnose patients with this illness. The diagnosis requires the presence of a monoclonal IgM component and bone marrow lymphoid infiltration must be demonstrated. In addition, other small B-cell lymphoid neoplasms with plasma cell differentiation must be discarded. Although the clinical picture is highly heterogeneous, the diagnosis is much easier today compared to the past, since now we can demonstrate the presence of somatic mutations, especially the L265P mutation in the MYD88 gene, highly characteristic of WM (> 90% of the patients), followed by the WHIM-like mutations in the CXCR4 gene (∼ 35%). The identification of these mutations is very important, because they can modulate the response to new treatments with Bruton’s tyrosine kinase (BTK) inhibitors. Thus, the conventional prognostic factors that predict the outcome of these patients (anemia, thrombopenia, high M component, high B2M, and advanced age), must be complemented with the genetic evaluation of the patient, that can help us in the prediction of the risk of transformation from asymptomatic to symptomatic forms (Del6q) and/or from indolent forms of the disease to aggressive lymphomas (CD79b mutations).Keywords: Waldenström’s macroglobulinemia, IgM-MGUS, pathology, biology, diagnosis, prognosis
Published: 2021

5. Bioaccumulation and Biotransformation of BDE‐47 Using Zebrafish Eleutheroembryos ( Danio rerio )

Author: Paloma De Oro-Carretero and Jon Sanz Landaluze
Subjects: biology, Biotransformation, Chemistry, Environmental chemistry, Bioaccumulation, Health, Toxicology and Mutagenesis, Danio, Environmental Chemistry, Química analítica, biology.organism_classification, Zebrafish
Abstract: Polybrominated diphenyl ethers (PBDEs) industrially used as flame retardants are nowadays considered emerging pollutants as they are endocrine disrupting chemicals (EDCs), persistent in the environment, bioaccumulative and in addition, its hydroxylated (OH-BDEs) and methoxylated (MeO-BDEs) metabolites have similar ecotoxic properties. The aim of this work was to develop an analytical method to be applied in the study of the bioconcentration and biotransformation of BDE-47 due to its bioavailability, toxicity and high persistence and abundance in environmental samples, including humans. So, a dependable ultrasonic extraction process followed to dispersive SPE clean-up step and GC-MS-μECD detection has worked out for the determination of BDE-47 and its main biotransformation products (MeO-BDEs and OH-BDEs), considering the polarity difference. In addition, an alternative method to bioconcentration official guideline OECD 305, developed previously with zebrafish (Danio rerio) eleutheroembryos (i.e., hatched but not yet free feeding embryos) is used, reducing dramatically the animal suffering but also time and reagents. Bioconcentration factors (BCF) were calculated using first order one-compartment toxicokinetic model. The profiles found show rapid absorption in the first hours of larval development and great bioaccumulative with capacity, finding bioconcentration factors (BCF) of 6631 and 44210 at nominal concentrations of 10 and 1 μg·L-1 (< 1% LC50), respectively. Metabolization studies show increasing concentrations of the metabolites BDE-28, 2'-OH-BDE-28 and 5-MeO-BDE-47 throughout the exposure time. The results obtained show the feasibility of the method for bioaccumulation and opens the possibility of metabolic studies with zebrafish eleutheroembryos, which is a very underdeveloped field without official testing or regulation.
Published: 2023

6. Valorization of brewer’s spent grain by furfural recovery/removal from subcritical water hydrolysates by pervaporation

Author: Patricia Alonso-Riaño, Alba E. Illera, Mariana S.T. Amândio, Ana M.R.B. Xavier, Sagrario Beltrán, and M. Teresa Sanz
Subjects: Subcritical water hydrolysates, Pervaporation, Chemical engineering, Biología, Filtration and Separation, Ingeniería química, PDMS/POMS membranes, Furfural, Biology, Brewer’s spent grain, Analytical Chemistry, Brewer's spent grain
Abstract: This work is focused on the development of a sustainable process for the valorisation of the main by-product generated in the brewing industry, the brewer’s spent grain (BSG). A two-step process combining subcritical water treatment and pervaporation (PV) was proposed to hydrolyse the hemicelluloses fraction of this lignocellulosic biomass and further removal/recovery of some of the degradation products of sugars by using two different organophilic membranes, polydimethylsiloxane (PDMS) and polyoctilmethylsiloxane (POMS) membranes. Specifically, furfural is the dehydration product of pentoses and it is one of the top biomass-based chemicals being an important platform chemical. For synthetic binary mixtures, lower total permeation flux but higher enrichment factors for furfural were determined for POMS. When dealing with subW hydrolysates, POMS membranes yielded the highest furfural recovery, 94.1 %, with permeate concentrations as high as 40 g⋅L1 . Furthermore, it was assessed that PV is a suitable detoxification method that yielded a retentate nearly free of furfural allowing its use as growth media in the opposite to the subW hydrolysate with inhibitory furfural concentrations for microbial bioprocesses., This work was supported by the Agencia Estatal de Investigacion ´ [Grants No PID2019-104950RB-I00 / AEI / 10.13039/501100011033, TED2021-129311B-I00 and PDC2022-133443-I00] and the Junta de Castilla y Leon ´ (JCyL) and the European Regional Development Fund (ERDF) [grant number BU050P20]. P. Alonso-Riano ˜ predoctoral contract was funded by JCyL and the European Social Fund (ESF) by ORDEN EDU/556/2019 de 5 de junio. This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials UIDB/50011/2020, UIDP/50011/ 2020 & LA/P/0006/2020 financed by national funds through the FCT/ MEC (PIDDAC).
Published: 2023

7. Dynamic architecture and regulatory implications of the miRNA network underlying the response to stress in melon

Author: Alejandro Sanz-Carbonell, Gustavo Gómez, German Martinez, Maria Carmen Marques, Swedish Research Council, Knut and Alice Wallenberg Foundation, Sanz-Carbonell, Alejandro [0000-0002-1969-5557], Marqués, M. Carmen [0000-0001-8392-453X], Martínez, Germán [0000-0002-5215-0866], Gómez, Gustavo [0000-0003-3715-7792], Sanz-Carbonell, Alejandro, Marqués, M. Carmen, Martínez, Germán, and Gómez, Gustavo
Subjects: Crops, Agricultural, Melon, Transcript quantification, Period (gene), Computational biology, Biology, Regulation of the stress response in crops, 03 medical and health sciences, 0302 clinical medicine, Gene Expression Regulation, Plant, Stress, Physiological, Stress (linguistics), microRNA, Gene Regulatory Networks, Gene Silencing, Molecular Biology, 030304 developmental biology, 0303 health sciences, Structural organization, Abiotic stress, Cell Biology, MicroRNAs, Cucurbitaceae, RNA silencing, Phenotype, miRNA networks, 030220 oncology & carcinogenesis, sRNAs analisys, RNA Interference, Function (biology), Research Paper
Abstract: miRNAs are small RNAs that regulate mRNAs at both transcriptional and posttranscriptional level. In plants, miRNAs are involved in the regulation of different processes including development and stress-response. Elucidating how stress-responsive miRNAs are regulated is key to understand the global response to stress but also to develop efficient biotechnological tools that could help to cope with stress. Here, we describe a computational approach based on sRNA sequencing, transcript quantification and degradome data to analyse the accumulation, function and structural organization of melon miRNAs reactivated under seven biotic and abiotic stress conditions at two and four days post-treatment. Our pipeline allowed us to identify fourteen stress-responsive miRNAs (including evolutionary conserved such as miR156, miR166, miR172, miR319, miR398, miR399, miR894 and miR408) at both analysed times. According to our analysis miRNAs were categorized in three groups showing a broad-, intermediate- or narrow- response range. miRNAs reactive to a broad range of environmental cues appear as central components in the stress-response network. The strictly coordinated response of miR398 and miR408 (broad response-range) to the seven stress treatments during the period analysed here reinforces this notion. Although both, the amplitude and diversity of the miRNA-related response to stress changes during the exposition time, the architecture of the miRNA-network is conserved. This organization of miRNA response to stress is also conserved in rice and soybean supporting the conservation of miRNA-network organization in other crops. Overall, our work sheds light into how miRNA networks in plants organize and function during stress., The SNP&SEQ Platform is also supported by the Swedish Research Council and the Knut and Alice Wallenberg Foundation.
Published: 2019

8. A Bioinformatic Workflow for InDel Analysis in the Wheat Multi-Copy α-Gliadin Gene Family Engineered with CRISPR/Cas9

Author: María H. Guzmán-López, Miriam Marín-Sanz, Francisco Barro, Susana Sánchez-León, Ministerio de Ciencia e Innovación (España), Junta de Andalucía, European Commission, CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI), Guzmán-López, María H., Marín-Sanz, Miriam, Sánchez-León, Susana, Barro Losada, Francisco, Guzmán-López, María H. [0000-0003-0032-0058], Marín-Sanz, Miriam [0000-0002-0040-1053], Sánchez-León, Susana [0000-0002-9858-6171], and Barro Losada, Francisco [0000-0002-7652-229X]
Subjects: multi-gene, Gliadin, INDEL Mutation, wheat, CRISPR, Coding region, Celiac disease, Multi-target, Biology (General), Spectroscopy, Triticum, chemistry.chemical_classification, Gene Editing, food and beverages, General Medicine, Genomics, Amplicon, Computer Science Applications, Chemistry, Genome, Plant, QH301-705.5, Gliadins, Computational biology, Biology, Genes, Plant, Catalysis, Article, Multi-gene, Inorganic Chemistry, CRISPR/Cas, Gene family, Physical and Theoretical Chemistry, Indel, Molecular Biology, Gene, QD1-999, InDels, Cas9, multi-target, Organic Chemistry, Computational Biology, nutritional and metabolic diseases, Sequence Analysis, DNA, Usearch, Gluten, multi-copy, gluten, celiac disease, gliadins, Multi-copy, chemistry, CRISPR-Cas Systems
Abstract: This article belongs to the Special Issue Crop Genome Editing., The α-gliadins of wheat, along with other gluten components, are responsible for bread viscoelastic properties. However, they are also related to human pathologies as celiac disease or non-celiac wheat sensitivity. CRISPR/Cas was successfully used to knockout α-gliadin genes in bread and durum wheat, therefore, obtaining low gluten wheat lines. Nevertheless, the mutation analysis of these genes is complex as they present multiple and high homology copies arranged in tandem in A, B, and D subgenomes. In this work, we present a bioinformatic pipeline based on NGS amplicon sequencing for the analysis of insertions and deletions (InDels) in α-gliadin genes targeted with two single guides RNA (sgRNA). This approach allows the identification of mutated amplicons and the analysis of InDels through comparison to the most similar wild type parental sequence. TMM normalization was performed for inter-sample comparisons; being able to study the abundance of each InDel throughout generations and observe the effects of the segregation of Cas9 coding sequence in different lines. The usefulness of the workflow is relevant to identify possible genomic rearrangements such as large deletions due to Cas9 cleavage activity. This pipeline enables a fast characterization of mutations in multiple samples for a multi-copy gene family., This research was funded by the Spanish Ministry of Science and Innovation (Project PID2019-110847RB-I00), Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía (Project P20_01005), and the European Regional Development Fund (FEDER). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).
Published: 2021

9. Rho GTPase signaling in cancer progression and dissemination

Author: Remi Samain, Samantha George, Jaume Barcelo, Leonie Kohlhammer, Jose L. Orgaz, Eva Crosas-Molist, Victoria Sanz-Moreno, Oscar Maiques, Cancer Research UK, Barts Charity, and Comunidad de Madrid
Subjects: rho GTP-Binding Proteins, Senescence, Physiology, Cell, Inflammation, Disease, GTPase, Biology, Cell Movement, Neoplasms, Physiology (medical), Rho GTPases, Tumor Microenvironment, medicine, Animals, Humans, Epigenetics, Molecular Biology, Cancer, General Medicine, Clinical opportunities, medicine.disease, Signaling, Cell Transformation, Neoplastic, medicine.anatomical_structure, Apoptosis, Cancer research, medicine.symptom, Signal Transduction
Abstract: Rho GTPases are a family of small G proteins that regulate a wide array of cellular processes related to their key roles controlling the cytoskeleton. Cancer is a multistep disease caused by the accumulation of genetic mutations and epigenetic alterations, from the initial stages of cancer development when cells in normal tissues undergo transformation, to the acquisition of invasive and metastatic traits, responsible for a large number of cancer related deaths. In this review, we discuss the role of Rho GTPase signaling in cancer in every step of disease progression. Rho GTPases contribute to tumor initiation and progression, by regulating proliferation and apoptosis, but also metabolism, senescence, and cancer cell stemness. Rho GTPases play a major role in cell migration and in the metastatic process. They are also involved in interactions with the tumor microenvironment and regulate inflammation, contributing to cancer progression. After years of intensive research, we highlight the importance of relevant models in the Rho GTPase field, and we reflect on the therapeutic opportunities arising for cancer patients., The work was supported by Cancer Research UK (CRUK) C33043/A24478 (to V.S.-M., E.C.-M., O.M., and L.K.); Barts Charity (to V.S.M., R.S., and S.L.G.); The Harry J. Lloyd Charitable Trust (to J.L.O. and V.S.-M); and Comunidad de Madrid (Atraccion de Talento-2019-T1/BMD-13642) (to J.L.O.).
Published: 2022

10. Comparative evaluation of assays for IgM detection of rubella and measles infections

Author: Desirée Dafouz, Fernando de Ory, José Luis Muñoz, Pilar Balfagón, Mayte Pérez Olmeda, A. García, Juan Carlos Sanz, Jesús de la Fuente, María Ángeles Murillo, and Juan Camacho
Subjects: 0301 basic medicine, Microbiology (medical), 030106 microbiology, Antibodies, Viral, medicine.disease_cause, Measles, Rubella, Comparative evaluation, Serology, law.invention, Measles virus, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Humans, Electrochemiluminescence, 030212 general & internal medicine, Chemiluminescence, biology, business.industry, Rubella virus, biology.organism_classification, medicine.disease, Virology, Immunoglobulin M, business
Abstract: Background Serological diagnosis of infections due to measles and rubella viruses is done by IgM detection. The aim of this study was to comparatively evaluate commercial systems for detecting IgM against both viruses, including those of ELISA, in indirect and capture formats, chemiluminescence and electrochemiluminescence. Methods Seven (for rubella) and six (for measles) assays were studied. One hundred and sixty two samples were included in the study (from 90 rubella and 72 measles cases), and all were analyzed in all the assays. Results The ranges of sensitivity, specificity and agreement for rubella were 94.8–100%, 52.4–100% and 75.5–98.1%, respectively. The corresponding ranges for measles assays were 87.0–100%, 53.3–100%, and 73.0–99.4%. Conclusion The best-performing assays were chemiluminescence (for measles and rubella IgM), and electrochemiluminescence (for rubella IgM).
Published: 2022

11. Health status of free‐ranging pure and cross‐mixed miniature swine population from Northeast Spain

Author: Albert Sanz, Francesc Closa-Sebastià, Jaume Martorell, E Casas, and Vicente Soler
Subjects: Veterinary medicine, Miniature pig, miniature pig, Swine, Population, Miniature swine, serology, health status, Biology, medicine.disease_cause, Health status, Hepatitis E virus, SF600-1100, medicine, Influenza A virus, Animals, PIGS, African Swine Fever, education, Swine Diseases, education.field_of_study, General Veterinary, hybrid, Brucellosis, Original Articles, medicine.disease, Hepatitis E, biology.organism_classification, Hybrid, Serology, Classical swine fever, Spain, Swine, Miniature, Original Article
Abstract: Background Miniature pigs have gained popularity as companion animals in the recent years in Spain. Due to the fact that their abandonment and crossing breeds with wild boars can cause severe problems, investigation about the health status is needed. Objectives The aim of this study was to determine their health status according to the clinical findings during physical examination and the results of antibody serology tests against selected infectious diseases. Methods Two‐hundred and eleven miniature pigs (Sus scrofa) were included in the study. Their origin, age, sex, housing conditions and diet were recorded. Results The housing of the animals ranged from wild animals to ones living in animal sanctuaries. The diet varied from a natural one in the wild to commercial and homemade food. Thirty animals out of two‐hundred and eleven were hybrids between miniature pigs and wild boars according to morphological characteristics. Antibody serology techniques of Influenza A virus, Hepatitis E virus, brucellosis, tuberculosis, African swine fever, Classical swine fever and Aujeszky's disease was performed. The prevalence for Influenza A was 5.30%, for Hepatitis E was 5.35% and the rest tested negative. It is important to control and monitor these zoonotic infections to prevent Public Health problems. Conclusions The results obtained from this investigation demonstrated that the animals' health status in this study is optimal and the diseases prevalence is similar or minor when compared to previous studies. This study confirms the hybridization of miniature pig and wild boar in Catalonia., This paper describes a research project about health status of free‐ranging pure and cross‐mixed miniature swine population from North East Spain based on analysis of diet, environment, clinical findings, physical examination, and antibody serology techniques.
Published: 2022

12. Comparison of Cas9 and Cas12a CRISPR editing methods to correct the W1282X-CFTR mutation

Author: Mafalda Bacalhau, Carlos M. Farinha, Lúcia Santos, David J. Sanz, Miquéias Lopes-Pacheco, Karen Mention, Kader Cavusoglu-Doran, and Patrick T. Harrison
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, Cystic Fibrosis, CRISPR-Associated Proteins, Nonsense mutation, Nonsense-mediated decay, Cystic Fibrosis Transmembrane Conductance Regulator, medicine.disease_cause, Cystic fibrosis, Cell Line, Homology directed repair, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, CRISPR-Associated Protein 9, Humans, Medicine, CRISPR, Gene, Gene Editing, Mutation, Endodeoxyribonucleases, biology, business.industry, medicine.disease, Molecular biology, Cystic fibrosis transmembrane conductance regulator, 030104 developmental biology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, biology.protein, CRISPR-Cas Systems, business
Abstract: Background W1282X-CFTR variant (c.3846G>A) is the second most common nonsense cystic fibrosis (CF)-causing mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Even though remarkable breakthroughs have been done towards CF treatment with the approval of four CFTR protein modulators, none of these are approved for patients with nonsense mutations. CRISPR gene editing tools can be of great value to permanently correct the genetic defects caused by these mutations. Methods We compared the capacity of homology-directed repair (HDR) mediated by Cas9 or Cas12a to correct W1282X CFTR mutation in the CFF-16HBEge W1282X CFTR cell line (obtained from CFF), using Cas9/gRNA and Cas12a/gRNA ribonucleoproteins (RNPs) and single strand DNA (ssODN) oligonucleotide donors. Results Cas9 shows higher levels of correction than Cas12a as, by electroporating cells with Cas9 RNPs and ssODN donor, nearly 18% of precise editing was achieved compared to just 8% for Cas12a. Such levels of correction increase the abundance of CFTR mRNA and protein, and partially restore CFTR function in the pool of edited cells to 18% of WT CFTR function. Moreover, homozygous corrected clones produced levels of mRNA, protein, and function comparable to those of cells expressing WT CFTR. Conclusion Altogether, this work demonstrates the potential of gene editing as a therapeutic strategy for CF directly correcting the root cause of the disease.
Published: 2022

13. SwissGenVar: A platform for clinical grade interpretation of genetic variants to foster personalized health care in Switzerland

Author: Kraemer, Dennis, Terumalai, Dillenn, Famiglietti, Maria Livia, Filges, Isabel, Joset, Pascal, Koller, Samuel, Maurer, Fabienne, Meier, Stéphanie, Nouspikel, Thierry, Sanz, Javier, Zweier, Christiane, Abramowicz, Marc, Berger, Wolfgang, Cichon, Sven, Schaller, André, Superti-Furga, Andrea, Barbié, Valérie, Rauch, Anita, and University of Zurich
Subjects: 11124 Institute of Medical Molecular Genetics, expert, 10039 Institute of Medical Genetics, NGS, genotype, 570 Life sciences, biology, 610 Medicine & health, personalized medicine, SwissGenVar, Switzerland, curated variant interpretation, national mutation database, phenotype database
Published: 2023

14. CanScreen5, a global repository for breast, cervical and colorectal cancer screening programs

Author: Zhang, Li, Mosquera, Isabel, Lucas, Eric, Rol, Mary Luz, Carvalho, Andre L., Basu, Partha, Sadowski, Daniel, Natasha, Bartlett, Budd, Alison, Nessa, Ashrafun, De Brabander, Isabel, Haelens, Annemie, Pringels, Sarah, Tairo, Jonas, Hofvind, Solveig, Burrion, J. B., Valerianova, Zdravka, Tinmouth, Jill, Law, Cindy, Ebenuwah, Simbi, McCurdy, Bronwen, Janik, Beata, Pupwe, George, Groeneveld, Linn Fenna, Skare, Gry Baadstrand, Layne, Penelope, Sarkeala, Tytti, Chaila, Mwate Joseph, Kaminski, Michal, Kinel, Beata, Lissowska, Jolanta, Mumukunde, Inga, Rodrigues, Vitor, Rodriguez, Robinson, Perez Sanz, Elena, Zubizarreta Alberdi, Raquel, Ronco, Guglielmo, Antoljak, Natasa, Nakic, Dinka, Plazanin, Davor, Parun, Andrea Supe, Goossens, Mat, Nowakowski, Andrzej, de Koning, Harry, Dams, Els, Martin, Asha, Epermane, Mara, Jankovska, Natalja, Antle, Scott, Fracheboud, Jacques, Toes-Zoutendijk, Esther, van Agt, Heleen M. E., Budewig, Karen, Stomper, Barbara, Anttila, Ahti, McLeish, Sorana, Ramssl-Sauer, Alexandra, Ziniel, Georg, Kyprianou, Theopisti, Pavlou, Pavlos, Kaliva, Fofo, Tsantidou, Maria, Zhang, Shaokai, Xu, Huifang, Mushtaq, Wali, Paredes Barragan, Biviana, Montalvo, Alexandra, de la Torre Santos, Ana Victoria, Guertin, Marie-Helene, Fournier, Sarah, Duport, Nicolas, Majek, Ondrej, Ngo, Ondrej, Ivanus, Urska, Jarm, Katja, Primic-Zakelj, Maja, de Correa, Flavia Miranda, Migowski, Arn, Cancela, Marianna, Gallardo, Patricia, Fattore, Gisel, Puello, Adrian, Polanco, Victor, Ascunce Elizaga, Nieves, Fabri, Valerie, Mantellini, Paola, Zappa, Marco, Kellen, Eliane, Lynge, Elsebeth, Kaab-Sanyal, Vanessa, Malek, Daniela, Chami, Youssef, Ivanauskiene, Rugile, Bandhoe, Nensy, Dillenbourg, Claire, Heckters, Karin, Scharpantgen, Astrid, Mariela Ruiz, Oris, Mireya Gonzalez, Geneva, Arenas, Elsa, Palacios Cacacho, Eduardo Alberto, Pomata, Alicia, Navarro, Eliza, Mencia, Milva, Abreu Ruiz, Gisela, Campoverde, Ruth, Camel, Claudia, Donis, Rocio, Ines Sandoval, Yolanda, Garcia, Heidy, Isabel Roldan, Omaira, del Carmen Moreno, Teresa, Morales Velado, Mario, Merino, Gina, Rios, Juvenal A., Marte, Sabrina, Oliva Hernandez, Reina, Anea Chacon, Marina, Isabel Ruiz, Xiomara, Hernandez Vivas, Xiomara del Carmen, Ivan Gonzalez, Roger, Medal Ruiz, Damaris Isabel, Ortega, Lourdes, Matos Orbegozo, Andrea, Chuquiyauri Haro, Carlos Adolfo, Dalmas, Miriam, Unlu, Fahriye, Abousselham, Loubna, De Waldt, Rose-Marie, Buys, Charlotte, Hanna, Yasine, Williams, Cathi-Ann, Ottey, Londi-Ann, Philbert-Cyr, Shana, Emmanuel, Crissah, Jemmott, Alexandra, Alberto de Miranda, Nuno Augusto, Kioupi, Stala, Asnake, Takelech Moges, Attia, Adel A., Tshisimogo, Gontse, Seema, Lame, Banda, Jonathan Chiwanda, Mustapha, Feisul Idzwan, Mugolo, Rosita Paulo, de Miguel Juliao, Reginaldo Alice, Nyangasi, Mary, Mwenda, Valerian, Ferreira, Sonia Tavares, Barbosa, Carla, Makua, Manala, Bakare, Yacubu Herve Julius, Charles, Myanna, Charles, Leandra, Edwards-France, Vera, Sewtahal, Cheshta, Kebirungi, Bridget, Rwabinumi, Mugabe Frank, Williams, Valarie, Zachariah, Oritta, Scott, Arlitha, Deleveaux, Camille, Campbell, Martin, Ferreira, Cesaltina, Perera, Suraj, Silva, Padmaka, Kumarapeli, Vindya, Grant-Tate, Merisa, Tulloch, Cherie, Saika, Kumiko, Lee, Kyeongmin, Jun, Jae Kwan, Mukete, Sona Franklin, Dimitrov, Plamen, Momkuviene, Vaida, Zaksas, Viaceslavas, Veerus, Piret, Bric, Tatjana Kofol, Mlakar, Dominika Novak, Skrjanec, Ana Lucija, Zakotnik, Jozica Maucec, Skhirtladze, Tamar, Xuereb, Stephanie, Colquhoun, Carol, Sangrajrang, Suleeporn, Eshwar, Kumar, Stanners, Greig, Black, Roger, Andreassen, Trude, Budai, Andras, Dobrossy, Lajos, Kovacs, Attila, Nicula, Florian, Portillo, Isabel, Miren Altzibar, Jone, Arenaza, Edurne, Simango, Ndabaningi, Espinas, Josep A., Glinton-Rolle, Constance, Anews-Barr, Jeanette, Capote, Mariana, Fazzino, Marisa, Armstrong, Claire, Gamble, Andrew, Mc Innes, Kenneth, Wright, Suzanne, Clayton, Helen, Latinovic, Radoslav, Mackie, Anne, Rimmer, Janet, Hall, Clare, Elfstrom, Klara Miriam, Tornberg, Sven, Zorzi, Manuel, Leja, Marcis, Rezeberga, Dace, Hagenimana, Marc, Hamers, Francoise, Rogel, Agnes, Assogba, Frank, Fitzpatrick, Patricia, Arbyn, Marc, Figueroa, Jacqueline, Rovelo, Alex, Salinas, Erosloa, Yused Arguello, Elias, Milano Castillo, Adriana, Rosas, Velia, Spanik, Stanislav, Houmann, Merete Ronmos, Johansen, Dorte, Dillner, Joakim, Oswal, Kunal, Huang, Yubei, Siala, Ismail M., Candeur, Michel, Hoeck, Sarah, Borras, Josep M., Bleyen, Luc, Guzha, Bothwell Takaingofa, Mesmin Olivier, Adie Yao, Fasching, Elisabeth, Gesundheit, Alexander Gollmer, Taohid, Tonoy, Bencomo, Walkiria Bermejo, Tejada, Darbelis, Valletta, Joseph Psaila, Nisbett, Judy, Baptiste, Damaris, Layne, Melanie Ann, and CanScreen5 Collaborators
Subjects: Chemistry, Human medicine, Biology
Abstract: In the first results from an ongoing global cancer screening data repository, screening program organization was better overall in Europe compared to other continents; however, there were substantial gaps in implementation across both high- and low-resource settings. The CanScreen5 project is a global cancer screening data repository that aims to report the status and performance of breast, cervical and colorectal cancer screening programs using a harmonized set of criteria and indicators. Data collected mainly from the Ministry of Health in each country underwent quality validation and ultimately became publicly available through a Web-based portal. Until September 2022, 84 participating countries reported data for breast (n = 57), cervical (n = 75) or colorectal (n = 51) cancer screening programs in the repository. Substantial heterogeneity was observed regarding program organization and performance. Reported screening coverage ranged from 1.7% (Bangladesh) to 85.5% (England, United Kingdom) for breast cancer, from 2.1% (Cote d'Ivoire) to 86.3% (Sweden) for cervical cancer, and from 0.6% (Hungary) to 64.5% (the Netherlands) for colorectal cancer screening programs. Large variability was observed regarding compliance to further assessment of screening programs and detection rates reported for precancers and cancers. A concern is lack of data to estimate performance indicators across the screening continuum. This underscores the need for programs to incorporate quality assurance protocols supported by robust information systems. Program organization requires improvement in resource-limited settings, where screening is likely to be resource-stratified and tailored to country-specific situations.
Published: 2023

15. Immunohistochemical characteristics of lateral bone augmentation using different biomaterials around chronic peri‐implant dehiscence defects: An experimental in vivo study

Author: Jae Kook Cha, Mariano Sanz, Rafael Plá, Ui Won Jung, Javier Sanz-Esporrin, and Fabio Vignoletti
Subjects: Vascular Endothelial Growth Factor A, Bone Regeneration, 0206 medical engineering, Biocompatible Materials, 02 engineering and technology, Andrology, 03 medical and health sciences, chemistry.chemical_compound, Dogs, 0302 clinical medicine, In vivo, Animals, Bone regeneration, Dental Implants, biology, Biomaterial, Membranes, Artificial, 030206 dentistry, 020601 biomedical engineering, Vascular endothelial growth factor, chemistry, Bone Substitutes, Guided Tissue Regeneration, Periodontal, Osteocalcin, biology.protein, Alkaline phosphatase, Immunohistochemistry, Cattle, Implant, Oral Surgery
Abstract: Aim To investigate the immunohistochemical characteristics of a highly porous synthetic bone substitute and a cross-linked collagen membrane for guided bone regeneration. Methods Three experimental groups were randomly allocated at chronic peri-implant dehiscence defect in 8 beagle dogs: (i) biphasic calcium phosphate covered by a cross-linked collagen membrane (test group), (ii) deproteinized bovine bone mineral covered by a natural collagen membrane (positive control) and (iii) no treatment (negative control). After 8 and 16 weeks of submerged healing, dissected tissue blocks were processed for immunohistochemical analysis. Seven antibodies were used to detect the remaining osteogenic and angiogenic potential, and quantitative immunohistochemical analysis was done by software. Results The antigen reactivity of alkaline phosphatase was significantly higher in the test group compared to the positive and negative controls, and it maintained till 16 weeks. The intensity of osteocalcin was significantly higher in the positive control at 8 weeks than the other groups, but significantly decreased at 16 weeks and no difference was found between the groups. A significant large number of TRAP-positive cells were observed in the test group mainly around the remaining particles at 16 weeks. The angiogenic potential was comparable between the groups showing no difference in the expression of transglutaminase II and vascular endothelial growth factor. Conclusion Guided bone regeneration combining a highly porous biphasic calcium phosphate synthetic biomaterial with a crosslinked collagen membrane, resulted in extended osteogenic potential when compared to the combination of deproteinized bovine bone mineral and a native collagen membrane.
Published: 2021

16. Blocking von Willebrand factor free thiols inhibits binding to collagen under high and pathological shear stress

Author: Thomas A. J. McKinnon, Alfonso De Simone, Alain Chion, Michael Laffan, Golzar Mobayen, Harrison E R O'Brien, Yan Xu, X. Frank Zhang, Maximo Sanz-Hernandez, Susan Shapiro, British Heart Foundation, O'Brien, H. E. R., Zhang, X. F., Sanz-Hernandez, M., Chion, A., Shapiro, S., Mobayen, G., Xu, Y., De Simone, A., Laffan, M. A., and Mckinnon, T. A. J.
Subjects: collagen, GLYCOPROTEIN IB, FLOW, PROTEIN, von Willebrand factor, 030204 cardiovascular system & hematology, 0302 clinical medicine, hemic and lymphatic diseases, thrombosi, VWF, Platelet, LINKED GLYCOSYLATION, 1102 Cardiorespiratory Medicine and Haematology, thiols, biology, Chemistry, Atomic force microscopy, shear stre, thiol, Hematology, PLATELET-ADHESION, medicine.anatomical_structure, cardiovascular system, Life Sciences & Biomedicine, Protein Binding, circulatory and respiratory physiology, Blood Platelets, congenital, hereditary, and neonatal diseases and abnormalities, Flexibility (anatomy), shear stress, FORCE, 03 medical and health sciences, Platelet Adhesiveness, Von Willebrand factor, medicine, Shear stress, Humans, Sulfhydryl Compounds, thrombosis, Binding function, Science & Technology, ELONGATION, 1103 Clinical Sciences, ENDOTHELIAL-CELLS, SELF-ASSOCIATION, Peripheral Vascular Disease, Cardiovascular System & Hematology, Glycoprotein Ib, Acute exposure, Cardiovascular System & Cardiology, Biophysics, biology.protein, Stress, Mechanical
Abstract: Background Von Willebrand factor (VWF) contains a number of free thiols, the majority of which are located in its C-domains, and these have been shown to alter VWF function, However, the impact of free thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Methods VWF free thiols were blocked with N-ethylmaleimide and flow assays performed under high and pathological shear rates to determine the impact on platelet capture and collagen binding function. Atomic force microscopy (AFM) was used to probe the interaction of VWF with collagen and molecular simulations conducted to determine the effect of free thiols on the flexibility of the VWF-C4 domain. Results Blockade of VWF free thiols reduced VWF-mediated platelet capture to collagen in a shear-dependent manner, with platelet capture virtually abolished above 5000 s-1 and in regions of stenosis in microfluidic channels. Direct visualization of VWF fibers formed under extreme pathological shear rates and analysis of collagen-bound VWF attributed the effect to altered binding of VWF to collagen. AFM measurements showed that thiol-blockade reduced the lifetime and strength of the VWF-collagen bond. Pulling simulations of the VWF-C4 domain demonstrated that with one or two reduced disulphide bonds the C4 domain has increased flexibility and the propensity to undergo free-thiol exchange. Conclusions We conclude that free thiols in the C-domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognized role for VWF free thiols.
Published: 2021

17. Pseudomonas aeruginosa: an antibiotic resilient pathogen with environmental origin

Author: José Luis Martínez, Fernando Sanz-García, Sara Hernando-Amado, and Pablo Laborda
Subjects: Microbiology (medical), Infectivity, Cystic Fibrosis, biology, medicine.drug_class, Pseudomonas aeruginosa, Antibiotics, Virulence, Antimicrobial, biology.organism_classification, medicine.disease_cause, Microbiology, Anti-Bacterial Agents, Infectious Diseases, Antibiotic resistance, medicine, Humans, Pseudomonas Infections, Pathogen, Ecosystem, Bacteria
Abstract: Pseudomonas aeruginosa, a bacterium characterized for its low antibiotics' susceptibility, is one of the most relevant opportunistic pathogens, causing infections at hospitals and in cystic fibrosis patients. Besides its relevance for human health, P. aeruginosa colonizes environmental ecosystems; therefore the elements driving its infectivity and antibiotic resistance must be analyzed from a One-Health perspective. Although some epidemic clones have been described, there are not specific lineages linked to infections, suggesting that P. aeruginosa virulence and antibiotic resistance determinants evolved in nature to play functions other than infecting the human host and avoiding antimicrobial treatment. Herein, we review current information on the population structure of P. aeruginosa and on the functional role that its resistance and virulence determinants have in non-clinical ecosystems.
Published: 2021

18. Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection

Author: Lin Wang, Marcelo Fernandez-Vina, E. Steve Woodle, F. Eun-Hyung Lee, Natalie S. Haddad, Madhav C. Menon, Alin Girnita, Patrick Ahearn, Andrea Morrison-Porter, Aditya Jain, Howard M. Gebel, Ignacio Sanz, Tanuja Yalamarti, Susan Hartzell, Jonathan S. Maltzman, Yorg Azzi, Enver Akalin, Paolo Cravedi, and Marzuq Billah
Subjects: medicine.medical_specialty, Kidney, biology, business.industry, General Medicine, medicine.disease, Organ transplantation, Virus, Epitope, medicine.anatomical_structure, Immunoglobulin class switching, Clinical Research, Nephrology, Immunology, Cohort, biology.protein, Medicine, Antibody, business, Kidney transplantation
Abstract: BACKGROUND: Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies against the virus are thought to offer protection, but a thorough characterization of anti–SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. METHODS: We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1–4, and IgA antibodies against five distinct viral epitopes. RESULTS: Kidney transplant recipients showed lower levels of total IgG antitrimeric spike (S), S1, S2, and receptor binding domain (RBD) but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG antispike protein epitopes were also lower than in immunocompetent controls. Anti–SARS-CoV-2 antibodies were predominantly IgG1 and IgG3, with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. CONCLUSIONS: Kidney transplant recipients mount early anti–SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19. PODCAST: This article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2021_11_23_briggsgriffin112321.mp3
Published: 2021

19. Lumefantrine attenuates Plasmodium falciparum artemisinin resistance during the early ring stage

Author: Prapon Wilairat, Maria G. Gomez-Lorenzo, Thanat Chookajorn, Kesinee Chotivanich, Krittikorn Kümpornsin, Laura M. Sanz, Cristina de Cozar, Marcus C. S. Lee, Namfon Kotanan, Duangkamon Loesbanluechai, Nicholas J. White, and Francisco-Javier Gamo
Subjects: Drug, Regular article, Artemisinins, media_common.quotation_subject, Plasmodium falciparum, Protozoan Proteins, Drug resistance, Infectious and parasitic diseases, RC109-216, Pharmacology, Lumefantrine, Antimalarials, chemistry.chemical_compound, Isobologram, parasitic diseases, medicine, Humans, Pharmacology (medical), Artemether, Malaria, Falciparum, Artemisinin, media_common, biology, business.industry, biology.organism_classification, medicine.disease, Malaria, Infectious Diseases, chemistry, Parasitology, business, medicine.drug
Abstract: Emerging artemisinin resistance in Plasmodium falciparum malaria has the potential to become a global public health crisis. In Southeast Asia, this phenomenon clinically manifests in the form of delayed parasite clearance following artemisinin treatment. Reduced artemisinin susceptibility is limited to the early ring stage window, which is sufficient to allow parasites to survive the short half-life of artemisinin exposure. A screen of known clinically-implemented antimalarial drugs was performed to identify a drug capable of enhancing the killing activity of artemisinins during this critical resistance window. As a result, lumefantrine was found to increase the killing activity of artemisinin against an artemisinin-resistant clinical isolate harboring the C580Y kelch13 mutation. Isobologram analysis revealed synergism during the early ring stage resistance window, when lumefantrine was combined with artemether, an artemisinin derivative clinically partnered with lumefantrine. These findings suggest that lumefantrine should be clinically explored as a partner drug in artemisinin-based combination therapies to control emerging artemisinin resistance., Graphical abstract Image 1, Highlights • Artemisinin booster compound screening targeting the early ring resistance window in Plasmodium falciparum was performed. • Lumefantrine improves the activity of artesunate against the parasite during the resistance window. • Artemether and lumefantrine are synergistic during the early ring stage resistance window.
Published: 2021

20. Nasogastric enteral feeding tubes modulate preterm colonization in early life

Author: B Chinea Jiménez, B Moreno-Sanz, I Castro Navarro, M Sáenz de Pipaón, L Fernández Álvarez, E Escribano Palomino, José M. Rodríguez, B Orgaz Martín, C Alba Rubio, and J Jara Pérez
Subjects: Neonatal intensive care unit, biology, Pediatrics, Perinatology and Child Health, Physiology, Colonization, biology.organism_classification, Isolation (microbiology), Enteral administration, Bacteria, Early life, Feces, Antibiotic resistance genes
Abstract: Background Preterm infants are generally fed through nasogastric enteral feeding tubes (NEFTs). The aim of this work was to evaluate the role of NEFTs in the initial colonization of the preterm gut and its evolution within the first 2 weeks after birth. Methods For this purpose, fecal and NEFT-derived samples from 30 preterm infants hospitalized in a neonatal intensive care unit (NICU) were collected from birth to the second week of life. Samples were cultivated in ten culture media, including three for the isolation of antibiotic-resistant microorganisms. Results Isolates (561) were identified by 16S ribosomal RNA gene sequencing. Although the first NEFTs inserted into the neonates after birth were rarely colonized, analysis of NEFTs and fecal samples over time revealed a significant increase in bacterial abundance, diversity, and detection frequency. Results showed a parallel colonization between time-matched NEFTs and fecal samples, suggesting an ongoing bidirectional transfer of bacteria from the neonatal gut to the NEFTs and vice versa. Conclusions In short-term hospitalization, length is by far the determinant factor for the early colonization of preterm infants. As NEFT populations reflect the bacterial populations that are colonizing the preterm in a precise moment, their knowledge could be useful to prevent the dissemination of antibiotic-resistant strains. Impact The hospital environment modulates preterm colonization immediately after birth. The colonization of preterm feces and NEFTs occurs in parallel. There is an ongoing bidirectional transfer of microorganisms from the neonatal gut to the NEFTs and vice versa. Bacterial communities inside NEFTs could act as reservoirs of antibiotic resistance genes. NEFT populations reflect the bacteria that are colonizing the preterm at a precise moment.
Published: 2021

21. Management of Persistent SARS-CoV-2 Infection in Patients with Follicular Lymphoma

Author: Roberto Trelles-Martínez, Francisco-Javier Peñalver, Carlos Guijarro, M. V. Velasco, Elia Pérez-Fernández, Gil Rodríguez-Caravaca, Pilar Martinez-Barranco, Lucia Villalon, Maria García-Roa, Karmele Arribalzaga, Juan Manuel Acedo-Sanz, Javier Marcos, Carolina Campelo, María José García-Bueno, and Pilar Ricard
Subjects: medicine.medical_specialty, Combination therapy, medicine.medical_treatment, Follicular lymphoma, Disease, Immunocompromised Host, Immunophenotyping, Recurrence, Internal medicine, medicine, Humans, Lymphoma, Follicular, Survival rate, COVID-19 Serotherapy, biology, SARS-CoV-2, business.industry, Immunization, Passive, COVID-19, Immunosuppression, Hematology, General Medicine, medicine.disease, Pneumonia, biology.protein, Antibody, business
Abstract: Introduction: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying hematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of 5 patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. Methods: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids, and convalescent plasma in 5 patients with FL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistent infection. Reverse transcriptase polymerase chain reaction tests and peripheral blood immunophenotype were performed for all patients. Results: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13–42) from the previous discharge. They all showed B-cell depletion by immunophenotyping, and no traces of immunoglobulin antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. Conclusion: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed FL patients treated with ICT.
Published: 2021

22. <scp>SARS‐CoV</scp> ‐2‐reactive antibody detection after <scp>SARS‐CoV</scp> ‐2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group

Author: Gabriela Sanz-Linares, Anna Sureda, Carlos Solano, Angel Cedillo, Elena Ferrer, Venancio Conesa-Garcia, Lucia Villalon, María Telesa Olave, Carmen Alonso, Blanca Ferrer-Lores, Montserrat Ruiz-García, I Espigado, José Luis Piñana, Ariadna Pérez, Valentín García-Gutiérrez, Ana Saus, Ana Facal-Malvar, Manuel Guerreiro, Lourdes Vázquez, Juan Montoro, Javier López-Jiménez, Jose Angel Hernandez-Rivas, David Navarro, Maria-Jesús Pascual, Lucía López-Corral, Rafael Hernani, Marta Garcia-Blazquez, Juan Luis Muñoz-Bellido, Gabriel Martin-Martin, Beatriz Gago, Rodrigo Martino, Sara Marcos-Corrales, and Andrés Sanchez-Salinas
Subjects: Oncology, medicine.medical_specialty, biology, business.industry, medicine.medical_treatment, Hematopoietic stem cell, Hematology, Disease, Odds ratio, Hematopoietic stem cell transplantation, medicine.disease, Lymphoma, Cell therapy, Vaccination, medicine.anatomical_structure, Internal medicine, medicine, biology.protein, Antibody, business
Abstract: This is a multicenter prospective observational study which included a large cohort (n = 397) of allogeneic (allo-HSCT) (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3 to 6 weeks after complete SARS-CoV-2 vaccination from February 1st 2021 to July 20th 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia
Published: 2021

23. Freeze-dried extract from onion (Allium cepa cv. Horcal) skin wastes: Extraction intensification and flavonoids identification

Author: María Teresa Sanz, Óscar Benito-Román, Sagrario Beltrán, and Beatriz Blanco
Subjects: Antioxidant, General Chemical Engineering, medicine.medical_treatment, Extraction, Biochemistry, Ultrasounds, chemistry.chemical_compound, Chemical engineering, Alimentos, medicine, Specific energy, Flavonoids, Chromatography, Ethanol, biology, Extraction (chemistry), Ingeniería química, biology.organism_classification, Solvent, chemistry, Process intensification, Food, Yield (chemistry), Allium, Quercetin, Onion, Food Science, Biotechnology
Abstract: In this work, the intensification of the extraction of flavonoids from dry onion skin wastes (DOSW) by Ultrasound Assisted Extraction (UAE) was investigated. Conventional stirred tank extraction was used to find the optimal temperature (37 °C) and solvent (ethanol 70%, v/v), providing 20.7 ± 0.4 mg QE/g DOSW after 1 h. In the UAE process, the amplitude of oscillation and the solvent-to-solid ratio were key parameters to control the specific energy used. Energies above 10 kJ/g OSW did not increase the extraction yield (maximum flavonoids content was 23.9 ± 0.2 mg QE/g DOSW), which could be obtained using amplitudes of 40%, high solvent-to-solid ratios (30 mL/g DOSW) and extraction times below 5 min. Although both extraction techniques provided similar profiles of phenolic compounds, being quercetin and quercetin-4′-O-glucoside the main flavonoids (7.4 mg/g DOSW and 10.4 mg/g DOSW, respectively), UAE increased the productivity up to 11.6 mg QE/(g DOSW·min), seven times higher than conventional extraction. The extraction kinetics was modeled and studied. The optimum extract was freeze-dried resulting in a solid powder rich in flavonoids (21%) which kept 90% of the antioxidant activity after 180 days of storage at temperatures below 4 °C., Junta de Castilla y León (JCyL) and the European Regional Development Fund (ERDF) [grant numbers BU301P18 and BU050P20] and the Agencia Estatal de Investigación [grant number PID2019-104950RB-I00/AEI/10.13039/501100011033 and PID2020-116716RJ-I00]. OBR’s postdoctoral contract through project BU301P18 is gratefully acknowledged. To JCyL and European Social Fund (ESF) for the contract of D. Benito-Bedoya and D. M. Aymara-Caiza through the YEI program, who participated in this work as technicians.
Published: 2021

24. Valorization of brewer’s spent grain by consecutive supercritical carbon dioxide extraction and enzymatic hydrolysis

Author: Patricia Alonso-Riaño, Rodrigo Melgosa, Ester Trigueros, Alba Ester Illera, Sagrario Beltrán, and M. Teresa Sanz
Subjects: Hydrolysis, Biología, Ingeniería química, General Medicine, Carbon Dioxide, Supercritical fluid extraction, Analytical Chemistry, Biorefinery, Brewer's spent grain, Chemical engineering, Enzymatic hydrolysis, Biomass, Edible Grain, Plant Structures, Biology, Food Science
Abstract: The double effect of supercritical carbon dioxide, sc-CO2, in a biorefinery concept applied to brewer’s spent grain (BSG) was assessed in this work. Extraction conditions to remove and valorize the lipophilic fraction were studied (20–40 MPa and 40–80 ◦C) obtaining a maximum yield of 5.70 ± 0.07 g/100 gBSG at 80 ◦C and 40 MPa. High pressures and temperatures resulted in higher content of total phenolic and flavonoid compounds, as well as higher antioxidant capacity. It was observed an improvement of the enzymatic hydrolysis yield by cellulase in the sc-CO2 treated BSG compared to the non-treated. This improvement could be partially attributed to the removal of the lipid fraction and to morphological changes of BSG after sc-CO2. Based on this double benefit, scCO2 can play an important role on biomass valorization., This work was supported by the Agencia Estatal de Investigación [grant number PID2019-104950RB-I00 / AEI / https://doi.org/10.130 39/501100011033] and the Junta de Castilla y León (JCyL) and the European Regional Development Fund (ERDF) [grant numbers BU301P18 and BU050P20]. E. Trigueros and P. Alonso-Riano ˜ predoctoral contracts were funded by JCyL and the European Social Fund (ESF) by ORDEN EDU/574/2018, de 28 de mayo and ORDEN EDU/556/2019, de 5 de junio, respectively.
Published: 2022

25. Quantitative Analysis of Periodontal Pathogens Using Real-Time Polymerase Chain Reaction (PCR)

Author: Elena Figuero, David Herrera, Mariano Sanz, and Mª José Marín
Subjects: 0301 basic medicine, biology, 030106 microbiology, Aggregatibacter actinomycetemcomitans, Campylobacter rectus, 030206 dentistry, biology.organism_classification, Molecular biology, Reverse transcription polymerase chain reaction, 03 medical and health sciences, 0302 clinical medicine, Real-time polymerase chain reaction, TaqMan, Tannerella forsythia, Multiplex, Porphyromonas gingivalis
Abstract: The quantitative polymerase chain reaction (qPCR) is a variant of PCR aimed to detect and quantify a targeted DNA molecule through the addition of probes labeled with fluorescent molecules that emit fluorescence within each amplification cycle, what results in fluorescence values proportional to the amount of accumulated PCR product. This chapter presents the detailed procedures for quantification of different periodontal pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Campylobacter rectus, and Fusobacterium spp.) using qPCR. It also includes the description of the most frequent problems encountered and how to solve them. In addition, a detailed protocol for multiplex qPCR to detect and quantify P. gingivalis and A. actinomycetemcomitans is included.
Published: 2022

26. Cutaneous squamous cell carcinoma in an autosomal-recessive Adams-Oliver syndrome patient with a novel frameshift pathogenic variant in the EOGT gene

Author: Meyer-Landolt, Lukas, Gaspar, Harald, Sanz, Javier, Trippel, Mafalda, Sabina, Gallati, and Rössler, Jochen
Subjects: 360 Social problems & social services, 360 Soziale Probleme, Sozialdienste, Genetics, 570 Life sciences, biology, 610 Medicine & health, 610 Medizin und Gesundheit, Genetics (clinical), 570 Biowissenschaften, Biologie
Abstract: Aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD) are the characteristic findings of Adams-Oliver syndrome (AOS). The variable clinical spectrum further includes cardiac, neurologic, renal, and ophthalmological findings. Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT. The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl from a refugee family of Iraq with consanguineous parents. She was born with a severe phenotype of AOS presenting a large ACC of the scalp with an underlying skull defect, which was often infected and inflamed. Afterward, additional ulceration developed. Furthermore, the girl showed microcephaly, TTLD on both hands and feet, and neurological findings: spastic paresis, epilepsy and suspicion of intellectual deficit. Molecular genetic analysis (next-generation sequencing) revealed a novel frameshift mutation in the EOGT gene in Exon 13 in homozygous constellation: c.1013dupA p.(Asn338Lysfs*24). A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. Treatment including surgical resection and focal irradiation was not curative and the girl deceased 6 months after initial diagnosis. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.
Published: 2022

27. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author: Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, 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Begun, Jakob, Behrends, Christian, Behrens, Georg, Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno, Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin, Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri, Besteiro, Sebastien, Betin, Virginie, Beyaert, Rudi, Bezbradica, Jelena, Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor, Bijian, Krikor, Billes, Viktor, Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa, Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, 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Isabelle, Corasaniti, Maria Tiziana, Corkery, Dale, Cordes, Nils, Cortese, Katia, Costa, Maria do Carmo, Costantino, Sarah, Costelli, Paola, Coto-Montes, Ana, Crack, Peter, Crespo, Jose, Criollo, Alfredo, Crippa, Valeria, Cristofani, Riccardo, Csizmadia, Tamas, Cuadrado, Antonio, Cui, Bing, Cui, Jun, Cui, Yixian, Cui, Yong, Culetto, Emmanuel, Cumino, Andrea, Cybulsky, Andrey, Czaja, Mark, Czuczwar, Stanislaw, D'Adamo, Stefania, D'Amelio, Marcello, D'Arcangelo, Daniela, D'Lugos, Andrew, D'Orazi, Gabriella, da Silva, James, Dafsari, Hormos Salimi, Dagda, Ruben, Dagdas, Yasin, Daglia, Maria, Dai, Xiaoxia, Dai, Yun, Dai, Yuyuan, Dal Col, Jessica, Dalhaimer, Paul, Dalla Valle, Luisa, Dallenga, Tobias, Dalmasso, Guillaume, Damme, Markus, Dando, Ilaria, Dantuma, Nico, Darling, April, Das, Hiranmoy, Dasarathy, Srinivasan, Dasari, Santosh, Dash, Srikanta, Daumke, Oliver, Dauphinee, Adrian, Davies, Jeffrey, Dávila, Valeria, Davis, Roger, Davis, Tanja, Dayalan Naidu, Sharadha, De Amicis, Francesca, De Bosscher, Karolien, De Felice, Francesca, De Franceschi, Lucia, De Leonibus, Chiara, de Mattos Barbosa, Mayara, De Meyer, Guido, De Milito, Angelo, De Nunzio, Cosimo, De Palma, Clara, De Santi, Mauro, De Virgilio, Claudio, De Zio, Daniela, Debnath, Jayanta, DeBosch, Brian, Decuypere, Jean-Paul, Deehan, Mark, Deflorian, Gianluca, DeGregori, James, Dehay, Benjamin, Del Rio, Gabriel, Delaney, Joe, Delbridge, Lea, Delorme-Axford, Elizabeth, Delpino, M Victoria, Demarchi, Francesca, Dembitz, Vilma, Demers, Nicholas, Deng, Hongbin, Deng, Zhiqiang, Dengjel, Joern, Dent, Paul, Denton, Donna, DePamphilis, Melvin, Der, Channing, Deretic, Vojo, Descoteaux, Albert, Devis, Laura, Devkota, Sushil, Devuyst, Olivier, Dewson, Grant, Dharmasivam, Mahendiran, Dhiman, Rohan, di Bernardo, Diego, Di Cristina, Manlio, Di Domenico, Fabio, Di Fazio, Pietro, Di Fonzo, Alessio, Di Guardo, Giovanni, Di Guglielmo, Gianni, Di Leo, Luca, Di Malta, Chiara, Di Nardo, Alessia, Di Rienzo, Martina, Di Sano, 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Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier, Hesselson, Daniel, Hetz, Claudio, Heussler, Volker, Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph, Hlavacek, William, Ho, Emmanuel, Ho, Idy, Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G Aaron, Hochstrasser, Mark, Hoet, Peter, Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina, Hombrebueno, Jose, Yi-Ren Hong, Chang-Won Hong, Hooper, Lora, Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael, Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias, Hubert, Virginie, Hubner, Christian, Hughes, Stephanie, 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Thomas, Jessen, Niels, Jewell, Jenna, Ji, Jing, Jia, Lijun, Jia, Rui, Jiang, Liwen, Jiang, Qing, Jiang, Richeng, Jiang, Teng, Jiang, Xuejun, Jiang, Yu, Jimenez-Sanchez, Maria, Jin, Eun-Jung, Jin, Fengyan, Jin, Hongchuan, Jin, Li, Jin, Luqi, Jin, Meiyan, Jin, Si, Jo, Eun-Kyeong, Joffre, Carine, Johansen, Terje, Johnson, Gail, Johnston, Simon, Jokitalo, Eija, Jolly, Mohit Kumar, Joosten, Leo, Jordan, Joaquin, Joseph, Bertrand, Ju, Dianwen, Ju, Jeong-Sun, Ju, Jingfang, Juárez, Esmeralda, Judith, Delphine, Juhász, Gábor, Jun, Youngsoo, Jung, Chang Hwa, Jung, Sung-Chul, Jung, Yong Keun, Jungbluth, Heinz, Jungverdorben, Johannes, Just, Steffen, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kaganovich, Daniel, Kahana, Alon, Kain, Renate, Kajimura, Shinjo, Kalamvoki, Maria, Kalia, Manjula, Kalinowski, Danuta, Kaludercic, Nina, Kalvari, Ioanna, Kaminska, Joanna, Kaminskyy, Vitaliy, Kanamori, Hiromitsu, Kanasaki, Keizo, Kang, Chanhee, Kang, Rui, Kang, Sang Sun, Kaniyappan, Senthilvelrajan, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanthasamy, Anumantha, Kanthasamy, Arthi, Kantorow, Marc, Kapuy, Orsolya, Karamouzis, Michalis, Karim, Md Razaul, Karmakar, Parimal, Katare, Rajesh, Kato, Masaru, Kaufmann, Stefan, Kauppinen, Anu, Kaushal, Gur, Kaushik, Susmita, Kawasaki, Kiyoshi, Kazan, Kemal, Ke, Po-Yuan, Keating, Damien, Keber, Ursula, Kehrl, John, Keller, Kate, Keller, Christian, Kemper, Jongsook Kim, Kenific, Candia, Kepp, Oliver, Kermorgant, Stephanie, Kern, Andreas, Ketteler, Robin, Keulers, Tom, Khalfin, Boris, Khalil, Hany, Khambu, Bilon, Khan, Shahid, Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha, Kho, Widuri, Khobrekar, Noopur, Khuansuwan, Sataree, Khundadze, Mukhran, Killackey, Samuel, Kim, Dasol, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Eun, Kim, Eun Young, Kim, Eun-Kyoung, Kim, Hak-Rim, Kim, Hee-Sik, Kim, Hyung Ryong, Kim, Jeong Hun, Kim, Jin Kyung, Kim, Jin-Hoi, Kim, Joungmok, Kim, Ju Hwan, Kim, Keun Il, Kim, Peter, Kim, Seong-Jun, Kimball, Scot, Kimchi, Adi, Kimmelman, Alec, Kimura, Tomonori, King, Matthew, Kinghorn, Kerri, Kinsey, Conan, Kirkin, Vladimir, Kirshenbaum, Lorrie, Kiselev, Sergey, Kishi, Shuji, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kitsis, Richard, Kittler, Josef, Kjaerulff, Ole, Klein, Peter, Klopstock, Thomas, Klucken, Jochen, Knævelsrud, Helene, Knorr, Roland, Ko, Ben, Ko, Fred, Ko, Jiunn-Liang, Kobayashi, Hotaka, Kobayashi, Satoru, Koch, Ina, Koch, Jan, Koenig, Ulrich, Kögel, Donat, Koh, Young Ho, Koike, Masato, Kohlwein, Sepp, Kocaturk, Nur, Komatsu, Masaaki, König, Jeannette, Kono, Toru, Kopp, Benjamin, Korcsmaros, Tamas, Korkmaz, Gözde, Korolchuk, Viktor, Korsnes, Mónica Suárez, Koskela, Ali, Kota, Janaiah, Kotake, Yaichiro, Kotler, Monica, Kou, Yanjun, Koukourakis, Michael, Koustas, Evangelos, Kovacs, Attila, Kovács, Tibor, Koya, Daisuke, Kozako, Tomohiro, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna, Kretz-Remy, Carole, Kroemer, Guido, Ktistakis, Nicholas, Kuchitsu, 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Da-Hye, Lee, Edward, Lee, Erinna, Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason, Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella, Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu, Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia, Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy, Levine, Beth, Lewis, Patrick, Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, 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Ignacio, Ramsden, David, Randow, Felix, Rangarajan, Pundi, Ranieri, Danilo, Rao, Hai, Rao, Lang, Rao, Rekha, Rathore, Sumit, Ratnayaka, J Arjuna, Ratovitski, Edward, Ravanan, Palaniyandi, Ravegnini, Gloria, Ray, Swapan, Razani, Babak, Rebecca, Vito, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas, Reigada, David, Reiling, Jan, Rein, Theo, Reipert, Siegfried, Rekha, Rokeya Sultana, Ren, Hongmei, Ren, Jun, Ren, Weichao, Renault, Tristan, Renga, Giorgia, Reue, Karen, Rewitz, Kim, Ribeiro de Andrade Ramos, Bruna, Riazuddin, S Amer, Ribeiro-Rodrigues, Teresa, Ricci, Jean-Ehrland, Ricci, Romeo, Riccio, Victoria, Richardson, Des, Rikihisa, Yasuko, Risbud, Makarand, Risueño, Ruth, Ritis, Konstantinos, Rizza, Salvatore, Rizzuto, Rosario, Roberts, Helen, Roberts, Luke, Robinson, Katherine, Roccheri, Maria Carmela, Rocchi, Stephane, Rodney, George, Rodrigues, Tiago, Rodrigues Silva, Vagner Ramon, Rodriguez, Amaia, Rodriguez-Barrueco, Ruth, Rodriguez-Henche, Nieves, Rodriguez-Rocha, Humberto, Roelofs, Jeroen, Rogers, Robert, Rogov, Vladimir, ROJO, Ana, Rolka, Krzysztof, Romanello, Vanina, Romani, Luigina, Romano, Alessandra, Romano, Patricia, Romeo-Guitart, David, Romero, Luis, Romero, Montserrat, Roney, Joseph, Rongo, Christopher, Roperto, Sante, Rosenfeldt, Mathias, Rosenstiel, Philip, Rosenwald, Anne, Roth, Kevin, Roth, Lynn, Roth, Steven, Rouschop, Kasper, Roussel, Benoit, Roux, Sophie, Rovere-Querini, Patrizia, Roy, Ajit, Rozieres, Aurore, Ruano, Diego, Rubinsztein, David, Rubtsova, Maria, Ruckdeschel, Klaus, Ruckenstuhl, Christoph, Rudolf, Emil, Rudolf, Rüdiger, Ruggieri, Alessandra, Ruparelia, Avnika Ashok, Rusmini, Paola, Russell, Ryan, Russo, Gian Luigi, Russo, Maria, Russo, Rossella, Ryabaya, Oxana, Ryan, Kevin, Ryu, Kwon-Yul, Sabater-Arcis, Maria, Sachdev, Ulka, Sacher, Michael, Sachse, Carsten, Sadhu, Abhishek, Sadoshima, Junichi, Safren, Nathaniel, Saftig, Paul, Sagona, Antonia, Sahay, Gaurav, Sahebkar, Amirhossein, Sahin, Mustafa, Sahin, Ozgur, Sahni, Sumit, Saito, Nayuta, Saito, Shigeru, Saito, Tsunenori, Sakai, Ryohei, Sakai, Yasuyoshi, Sakamaki, Jun-Ichi, Saksela, Kalle, Salazar, Gloria, Salazar-Degracia, Anna, Salekdeh, Ghasem, Saluja, Ashok, Sampaio-Marques, Belém, Sanchez, Maria Cecilia, Sanchez-Alcazar, Jose, Sanchez-Vera, Victoria, Sancho-Shimizu, Vanessa, Sanderson, J Thomas, Sandri, Marco, Santaguida, Stefano, Santambrogio, Laura, Santana, Magda, Santoni, Giorgio, Sanz, Alberto, Sanz, Pascual, Saran, Shweta, Sardiello, Marco, Sargeant, Timothy, Sarin, Apurva, Sarkar, Chinmoy, Sarkar, Sovan, Sarrias, Maria-Rosa, Sarkar, Surajit, Sarmah, Dipanka Tanu, Sarparanta, Jaakko, Sathyanarayan, Aishwarya, Sathyanarayanan, Ranganayaki, Scaglione, K Matthew, Scatozza, Francesca, Schaefer, Liliana, Schafer, Zachary, Schaible, Ulrich, Schapira, Anthony, Scharl, Michael, Schatzl, Hermann, Schein, Catherine, Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen, Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca, Schober, Romana, Schoijet, Alejandra, Schott, Micah, Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan, Schürmanns, Lea, Schwamborn, Jens, Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie, Scotto, Kathleen, Scovassi, A Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per, Seiliez, Iban, Seki, Ekihiro, Selleck, Scott, Sellke, Frank, Selsby, Joshua, Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, Setty, Subba Rao Gangi, Sgarbi, Gianluca, Sha, Ou, Shacka, John, Shah, Javeed, Shang, Dantong, Shao, Changshun, Shao, Feng, Sharbati, Soroush, Sharkey, Lisa, Sharma, Dipali, Sharma, Gaurav, Sharma, Kulbhushan, Sharma, Pawan, Sharma, Surendra, Shen, Han-Ming, Shen, Hongtao, Shen, Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher, Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra, Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind, Shutt, Timothy, Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno, Silva, Johnatas, Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel, Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit, Singh, Rajat, Singh, Shivendra, Singh, Shrawan, Singh, Sudha, Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios, Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya, Smertenko, Andrei, Smith, Matthew, Soenen, Stefaan, Sohn, Eun Jung, Sok, Sophia, Solaini, Giancarlo, Soldati, Thierry, Soleimanpour, Scott, Soler, Rosa, Solovchenko, Alexei, Somarelli, Jason, Sonawane, Avinash, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Kunhua, Song, Zhiyin, Soria, Leandro, Sorice, Maurizio, Soukas, Alexander, Soukup, Sandra-Fausia, Sousa, Diana, Sousa, Nadia, Spagnuolo, Paul, Spector, Stephen, Srinivas Bharath, M., St Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint, Stankov, Metodi, Stathopulos, Peter, Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan, Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne, Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana, Subauste, Carlos, Subbian, Selvakumar, Subirada, Paula, Sudhandiran, Ganapasam, Sue, Carolyn, Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, SUN, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen, Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel, Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen, Takahashi, Yoshinori, Takats, Szabolcs, Talwar, Priti, Tam, Chit, Tam, Shing Yau, Tampellini, Davide, Tamura, Atsushi, Tan, Chong Teik, Tan, Eng-King, Tan, Ya-Qin, Tanaka, Masaki, Tanaka, Motomasa, Tang, Daolin, Tang, Jingfeng, Tang, Tie-Shan, Tanida, Isei, Tao, Zhipeng, Taouis, Mohammed, Tatenhorst, Lars, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory, Taylor, Joan, Tchetina, Elena, Tee, Andrew, Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal, Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei, Testillano, Pilar, Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind, Thellung, Stefano, Thinwa, Josephine, Thirumalaikumar, V.P., Thomas, Sufi Mary, Thomes, Paul, Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir, Todi, Sokol, Todorova, Krassimira, Toivonen, Janne, Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon, Torgersen, Maria, Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina, Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo, Trelford, Charles, Tremel, Shirley, Trougakos, Ioannis, Tsao, Betty, Tschan, Mario, Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey, Tumbarello, David, Tumtas, Yasin, Tuñón, María, Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley, Tuxworth, Richard, Tyler, Jessica, Tyutereva, Elena, Uchiyama, Yasuo, Ugun-Klusek, Aslihan, Uhlig, Holm, Ułamek-Kozioł, Marzena, Ulasov, Ilya, Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir, Vaccari, Thomas, Vaccaro, Maria, Vahsen, Björn, Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria, Valko, Ayelén, Vallee, Richard, Valverde, Angela, Van Den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd, Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos, Vannini, Nicola, Vanrell, M Cristina, Vantaggiato, Chiara, Varano, Gabriele, Varela-Nieto, Isabel, Varga, Máté, Vasconcelos, M Helena, Vats, Somya, Vavvas, Demetrios, Vega-Naredo, Ignacio, Vega-Rubin-de-Celis, Silvia, Velasco, Guillermo, Velázquez, Ariadna, Vellai, Tibor, Vellenga, Edo, Velotti, Francesca, Verdier, Mireille, Verginis, Panayotis, Vergne, Isabelle, Verkade, Paul, Verma, Manish, Verstreken, Patrik, Vervliet, Tim, Vervoorts, Jörg, Vessoni, Alexandre, Victor, Victor, Vidal, Michel, Vidoni, Chiara, Vieira, Otilia, Vierstra, Richard, Viganó, Sonia, Vihinen, Helena, Vijayan, Vinoy, Vila, Miquel, Vilar, Marçal, Villalba, José, Villalobo, Antonio, Villarejo-Zori, Beatriz, Villarroya, Francesc, Villarroya, Joan, Vincent, Olivier, Vindis, Cecile, Viret, Christophe, Viscomi, Maria Teresa, Visnjic, Dora, Vitale, Ilio, Vocadlo, David, Voitsekhovskaja, Olga, Volonté, Cinzia, Volta, Mattia, Vomero, Marta, Von Haefen, Clarissa, Vooijs, Marc, Voos, Wolfgang, Vucicevic, Ljubica, Wade-Martins, Richard, Waguri, Satoshi, Waite, Kenrick, Wakatsuki, Shuji, Walker, David, Walker, Mark, Walker, Simon, Walter, Jochen, Wandosell, Francisco, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, PengWei, Wang, PeiPei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, wang, yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy, Wegrzyn, Grzegorz, Wehman, Ann, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver, Weihl, Conrad, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally, Whitton, J Lindsay, Whitworth, Alexander, Wiktorska, Katarzyna, Wildenberg, Manon, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin, Williams, Roger, Williamson, Peter, Wilson, Richard, Winner, Beate, Winsor, Nathaniel, Witkin, Steven, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, Jinrong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin, Yiu, Stephanie Pei Tung, Yoo, Young, Yoshida, Kiyotsugu, Yoshii, Saori, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond, Zacks, David, Zaffagnini, Gabriele, Zambelli, Vanessa, Zanella, Isabella, Zang, Qun, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott, Zeng, Jialiu, Zeng, Ju-deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin, Zhang, Leshuai, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, ZHOU, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith, Stallings, Christina, Tong, Chun-Kit, Ahmad, S. Tariq, Alim Al-Bari, M. Abdul, Bechara, Luiz R.G., Behrens, Georg M.N., Bhuiyan, Md. Shenuarin, Broaddus, V. Courtney, Buchan, J. Ross, Burón, M. Isabel, Carter, A. Brent, Chan, Matthew T.V., Choi, Augustine M.K., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew, D’Orazi, Gabriella, De Meyer, Guido R.Y., Delpino, M. Victoria, Distler, Jörg H.W., Dixon, Ian M.C., Dobson, Renwick C.J., 2nd Dorn, Gerald, Eissa, N. Tony, Engelsen, Agnete S.T., Fairlie, W. Douglas, Ferreira, Julio C.B., H.B., Ranjitha, Hanson, Phyllis I., Hejtmancik, J. Fielding, Ho, Idy H.T., Hobbs, G. Aaron, Hoet, Peter H.M., Huang, Michael L.H., Iyer, Anand Krishnan V., Johnson, Gail V.W., Joosten, Leo A.B., Karim, Md. Razaul, Kaufmann, Stefan H.E., Ko, Ben C.B., Leck, Lionel Y.W., Lima, Thania R.R., Livingston, J. Andrew, Martin, Alexandre P.J., Montes, L. Ruth, Murphy, J. Patrick, Ng, Charlene C.W., Nicolao, M. 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Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. Y., Antas, P., Antebi, A., Anton, Z., Anwar, T., Apetoh, L., Apostolova, N., Araki, T., Araki, Y., Arasaki, K., Araujo, W. L., Araya, J., Arden, C., Arevalo, M. -A., Arguelles, S., Arias, E., Arikkath, J., Arimoto, H., Ariosa, A. R., Armstrong-James, D., Arnaune-Pelloquin, L., Aroca, A., Arroyo, D. S., Arsov, I., Artero, R., Asaro, D. M. L., Aschner, M., Ashrafizadeh, M., Ashur-Fabian, O., Atanasov, A. G., Au, A. K., Auberger, P., Auner, H. W., Aurelian, L., Autelli, R., Avagliano, L., Avalos, Y., Aveic, S., Aveleira, C. A., Avin-Wittenberg, T., Aydin, Y., Ayton, S., Ayyadevara, S., Azzopardi, M., Baba, M., Backer, J. M., Backues, S. K., Bae, D. -H., Bae, O. -N., Bae, S. H., Baehrecke, E. H., Baek, A., Baek, S. -H., Baek, S. H., Bagetta, G., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bai, Y., Bairagi, N., Baksi, S., Balbi, T., Baldari, C. T., Balduini, W., Ballabio, A., Ballester, M., Balazadeh, S., Balzan, R., Bandopadhyay, R., Banerjee, S., Banreti, A., Bao, Y., Baptista, M. S., Baracca, A., Barbati, C., Bargiela, A., Barila, D., Barlow, P. G., Barmada, S. J., Barreiro, E., Barreto, G. E., Bartek, J., Bartel, B., Bartolome, A., Barve, G. R., Basagoudanavar, S. H., Bassham, D. C., Bast, R. C., Basu, A., Batoko, H., Batten, I., Baulieu, E. E., Baumgarner, B. L., Bayry, J., Beale, R., Beau, I., Beaumatin, F., Bechara, L. R. G., Beck, G. R., Beers, M. F., Begun, J., Behrends, C., Behrens, G. M. N., Bei, R., Bejarano, E., Bel, S., Behl, C., Belaid, A., Belgareh-Touze, N., Bellarosa, C., Belleudi, F., Bello Perez, M., Bello-Morales, R., Beltran, J. S. D. O., Beltran, S., Benbrook, D. M., Bendorius, M., Benitez, B. A., Benito-Cuesta, I., Bensalem, J., Berchtold, M. W., Berezowska, S., Bergamaschi, D., Bergami, M., Bergmann, A., Berliocchi, L., Berlioz-Torrent, C., Bernard, A., Berthoux, L., Besirli, C. G., Besteiro, S., Betin, V. M., Beyaert, R., Bezbradica, J. S., Bhaskar, K., Bhatia-Kissova, I., Bhattacharya, R., Bhattacharya, S., Bhattacharyya, S., Bhuiyan, M. S., Bhutia, S. K., Bi, L., Bi, X., Biden, T. J., Bijian, K., Billes, V. A., Binart, N., Bincoletto, C., Birgisdottir, A. B., Bjorkoy, G., Blanco, G., Blas-Garcia, A., Blasiak, J., Blomgran, R., Blomgren, K., Blum, J. S., Boada-Romero, E., Boban, M., Boesze-Battaglia, K., Boeuf, P., Boland, B., Bomont, P., Bonaldo, P., Bonam, S. R., Bonfili, L., Bonifacino, J. S., Boone, B. A., Bootman, M. D., Bordi, M., Borner, C., Bornhauser, B. C., Borthakur, G., Bosch, J., Bose, S., Botana, L. M., Botas, J., Boulanger, C. M., Boulton, M. E., Bourdenx, M., Bourgeois, B., Bourke, N. M., Bousquet, G., Boya, P., Bozhkov, P. V., Bozi, L. H. M., Bozkurt, T. O., Brackney, D. E., Brandts, C. H., Braun, R. J., Braus, G. H., Bravo-Sagua, R., Bravo-San Pedro, J. M., Brest, P., Bringer, M. -A., Briones-Herrera, A., Broaddus, V. 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V., Umekawa, M., Ungermann, C., Unno, R., Urbe, S., Uribe-Carretero, E., Ustun, S., Uversky, V. N., Vaccari, T., Vaccaro, M. I., Vahsen, B. F., Vakifahmetoglu-Norberg, H., Valdor, R., Valente, M. J., Valko, A., Vallee, R. B., Valverde, A. M., Van den Berghe, G., van der Veen, S., Van Kaer, L., van Loosdregt, J., van Wijk, S. J. L., Vandenberghe, W., Vanhorebeek, I., Vannier-Santos, M. A., Vannini, N., Vanrell, M. C., Vantaggiato, C., Varano, G., Varela-Nieto, I., Varga, M., Vasconcelos, M. H., Vats, S., Vavvas, D. G., Vega-Naredo, I., Vega-Rubin-de-Celis, S., Velasco, G., Velazquez, A. P., Vellai, T., Vellenga, E., Velotti, F., Verdier, M., Verginis, P., Vergne, I., Verkade, P., Verma, M., Verstreken, P., Vervliet, T., Vervoorts, J., Vessoni, A. T., Victor, V. M., Vidal, M., Vidoni, C., Vieira, O. V., Vierstra, R. D., Vigano, S., Vihinen, H., Vijayan, V., Vila, M., Vilar, M., Villalba, J. M., Villalobo, A., Villarejo-Zori, B., Villarroya, F., Villarroya, J., Vincent, O., Vindis, C., Viret, C., Viscomi, M. T., Visnjic, D., Vitale, I., Vocadlo, D. J., Voitsekhovskaja, O. V., Volonte, C., Volta, M., Vomero, M., Von Haefen, C., Vooijs, M. A., Voos, W., Vucicevic, L., Wade-Martins, R., Waguri, S., Waite, K. A., Wakatsuki, S., Walker, D. W., Walker, M. J., Walker, S. A., Walter, J., Wandosell, F. G., Wang, B., Wang, C. -Y., Wang, C., Wang, D., Wang, F., Wang, G., Wang, H., Wang, H. -G., Wang, J., Wang, K., Wang, L., Wang, M. H., Wang, M., Wang, N., Wang, P., Wang, Q. J., Wang, Q., Wang, Q. K., Wang, Q. A., Wang, W. -T., Wang, W., Wang, X., Wang, Y., Wang, Y. -Y., Wang, Z., Warnes, G., Warnsmann, V., Watada, H., Watanabe, E., Watchon, M., Wawrzynska, A., Weaver, T. E., Wegrzyn, G., Wehman, A. M., Wei, H., Wei, L., Wei, T., Wei, Y., Weiergraber, O. H., Weihl, C. C., Weindl, G., Weiskirchen, R., Wells, A., Wen, R. H., Wen, X., Werner, A., Weykopf, B., Wheatley, S. P., Whitton, J. L., Whitworth, A. J., Wiktorska, K., Wildenberg, M. E., Wileman, T., Wilkinson, S., Willbold, D., Williams, B., Williams, R. S. B., Williams, R. L., Williamson, P. R., Wilson, R. A., Winner, B., Winsor, N. J., Witkin, S. S., Wodrich, H., Woehlbier, U., Wollert, T., Wong, E., Wong, J. H., Wong, R. W., Wong, V. K. W., Wong, W. W. -L., Wu, A. -G., Wu, C., Wu, J., Wu, K. K., Wu, M., Wu, S. -Y., Wu, S., Wu, W. K. K., Wu, X., Wu, Y. -W., Wu, Y., Xavier, R. J., Xia, H., Xia, L., Xia, Z., Xiang, G., Xiang, J., Xiang, M., Xiang, W., Xiao, B., Xiao, G., Xiao, H., Xiao, H. -T., Xiao, J., Xiao, L., Xiao, S., Xiao, Y., Xie, B., Xie, C. -M., Xie, M., Xie, Y., Xie, Z., Xilouri, M., Xu, C., Xu, E., Xu, H., Xu, J., Xu, L., Xu, W. W., Xu, X., Xue, Y., Yakhine-Diop, S. M. S., Yamaguchi, M., Yamaguchi, O., Yamamoto, A., Yamashina, S., Yan, S., Yan, S. -J., Yan, Z., Yanagi, Y., Yang, C., Yang, D. -S., Yang, H., Yang, H. -T., Yang, J. -M., Yang, J., Yang, L., Yang, M., Yang, P. -M., Yang, Q., Yang, S., Yang, S. -F., Yang, W., Yang, W. Y., Yang, X., Yang, Y., Yao, H., Yao, S., Yao, X., Yao, Y. -G., Yao, Y. -M., Yasui, T., Yazdankhah, M., Yen, P. M., Yi, C., Yin, X. -M., Yin, Y., Yin, Z., Ying, M., Ying, Z., Yip, C. K., Yiu, S. P. T., Yoo, Y. H., Yoshida, K., Yoshii, S. R., Yoshimori, T., Yousefi, B., Yu, B., Yu, H., Yu, J., Yu, L., Yu, M. -L., Yu, S. -W., Yu, V. C., Yu, W. H., Yu, Z., Yuan, J., Yuan, L. -Q., Yuan, S., Yuan, S. -S. F., Yuan, Y., Yuan, Z., Yue, J., Yue, Z., Yun, J., Yung, R. L., Zacks, D. N., Zaffagnini, G., Zambelli, V. O., Zanella, I., Zang, Q. S., Zanivan, S., Zappavigna, S., Zaragoza, P., Zarbalis, K. S., Zarebkohan, A., Zarrouk, A., Zeitlin, S. O., Zeng, J., Zeng, J. -D., Zerovnik, E., Zhan, L., Zhang, B., Zhang, D. D., Zhang, H., Zhang, H. -L., Zhang, J., Zhang, J. -P., Zhang, K. Y. B., Zhang, L. W., Zhang, L., Zhang, M., Zhang, P., Zhang, S., Zhang, W., Zhang, X., Zhang, X. -W., Zhang, X. D., Zhang, Y., Zhang, Y. -D., Zhang, Y. -Y., Zhang, Z., Zhao, H., Zhao, L., Zhao, S., Zhao, T., Zhao, X. -F., Zhao, Y., Zheng, G., Zheng, K., Zheng, L., Zheng, S., Zheng, X. -L., Zheng, Y., Zheng, Z. -G., Zhivotovsky, B., Zhong, Q., Zhou, A., Zhou, B., Zhou, C., Zhou, G., Zhou, H., Zhou, J., Zhou, K., Zhou, R., Zhou, X. -J., Zhou, Y., Zhou, Z. -Y., Zhou, Z., Zhu, B., Zhu, C., Zhu, G. -Q., Zhu, H., Zhu, W. -G., Zhu, Y., Zhuang, H., Zhuang, X., Zientara-Rytter, K., Zimmermann, C. M., Ziviani, E., Zoladek, T., Zong, W. -X., Zorov, D. B., Zorzano, A., Zou, W., Zou, Z., Zuryn, S., Zwerschke, W., Brand-Saberi, B., Dong, X. C., Kenchappa, C. S., Lin, Y., Oshima, S., Rong, Y., Sluimer, J. C., Stallings, C. L., Tong, C. -K., and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Published: 2021

28. Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse

Author: Oskar Ortiz, Patricia García-Sanz, Samuel Alberquilla, Agnès Gruart, José M. Delgado-García, Oscar Solís, Adrián Sanz-Magro, Rosario Moratalla, Isabel Espadas, Ministerio de Ciencia e Innovación (España), Fundación Ramón Areces, European Commission, Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), and Junta de Andalucía
Subjects: Male, Cognitive Neuroscience, Hippocampus, Biology, Hippocampal formation, memory, Mice, hippocampal, Cellular and Molecular Neuroscience, Dopamine receptor D1, Dopamine receptor D2, Avoidance Learning, Animals, AcademicSubjects/MED00385, RNA, Small Interfering, CA1 Region, Hippocampal, long-term potentiation, Spatial Memory, Mice, Knockout, Neuronal Plasticity, learning, AcademicSubjects/SCI01870, Receptors, Dopamine D2, Long-term potentiation, Drd2−/−, CA3 Region, Hippocampal, Associative learning, Mice, Inbred C57BL, Dopamine receptor, Synapses, Synaptic plasticity, Original Article, AcademicSubjects/MED00310, Female, Neuroscience
Abstract: Dopamine receptors play an important role in motivational, emotional, and motor responses. In addition, growing evidence suggests a key role of hippocampal dopamine receptors in learning and memory. It is well known that associative learning and synaptic plasticity of CA3-CA1 requires the dopamine D1 receptor (D1R). However, the specific role of the dopamine D2 receptor (D2R) on memory-related neuroplasticity processes is still undefined. Here, by using two models of D2R loss, D2R knockout mice (Drd2-/-) and mice with intrahippocampal injections of Drd2-small interfering RNA (Drd2-siRNA), we aimed to investigate how D2R is involved in learning and memory as well as in long-term potentiation of the hippocampus. Our studies revealed that the genetic inactivation of D2R impaired the spatial memory, associative learning, and the classical conditioning of eyelid responses. Similarly, deletion of D2R reduced the activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. Our results demonstrate the first direct evidence that D2R is essential in behaving mice for trace eye blink conditioning and associated changes in hippocampal synaptic strength. Taken together, these results indicate a key role of D2R in regulating hippocampal plasticity changes and, in consequence, acquisition and consolidation of spatial and associative forms of memory., Spanish Ministries of Science and Innovation (PID2019-111693RBI00, PCIN-2015-098); Ramón Areces Foundation (ref 172275); European Union’s Horizon 2020 research and innovation program, AND-PD (grant agreement no. 848002 to R.M., BFU2017- 82375-R to A.G. and J.M.D.-G.); Health, Social Services and Equality (PI2019/09-3), CIBERNED CB06/05/0055 to R.M.); the Spanish Junta de Andalucía (BIO-122, PY18FR_823 to A.G. and J.M.D.-G.).
Published: 2020

29. Role of POLE and POLD1 in familial cancer

Author: Pau M. Munoz-Torres, Joan Brunet, Rebeca Sanz-Pamplona, August Vidal, Gemma Llort, Esther Darder, Victor Moreno, Teresa Ramón y Cajal, Laura Valle, Judith Balmaña, Marta Pineda, Tirso Pons, Xavier Matias-Guiu, Jesús del Valle, Lorena Magraner-Pardo, Rosa Aligué, Pilar Mur, Giacomo Cinnirella, Josep M. Piulats, Elia Grau, Lídia Feliubadaló, Sami Belhadj, Adriana Lopez-Doriga, Matilde Navarro, Conxi Lázaro, Sandra García-Mulero, Judit Sanz, Gabriel Capellá, Edgar Martin-Ramos, [Mur P, Del Valle J, Pineda M] Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. [García-Mulero S] Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. [Magraner-Pardo L] Prostate Cancer Clinical Research Unit. Spanish National Cancer Research Center (CNIO), Madrid, Spain. [Vidal A] Department of Pathology, Bellvitge University Hospital, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. [Balmana J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Generalitat de Catalunya, Fundación Olga Torres, and European Cooperation in Science and Technology
Subjects: fenómenos genéticos::variación genética::mutación::mutación de la línea germinal [FENÓMENOS Y PROCESOS], Proband, Polymerase proofreading–associated polyposis, Recte - Càncer - Aspectes genètics, Colorectal cancer, Genetic counseling, Population, Còlon - Càncer - Aspectes genètics, Biology, Article, Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation [PHENOMENA AND PROCESSES], Germline, PPAP, Endometrial cancer, Càncer colorectal, Malalties hereditàries, Ultramutated phenotype, medicine, Humans, Missense mutation, Poly-ADP-Ribose Binding Proteins, education, Allele frequency, Germ-Line Mutation, Genetics (clinical), Exonuclease domain, DNA Polymerase III, Genetics, education.field_of_study, Malalties transmissibles - Teoria germinal, POLD1, ultramutated phenotype, DNA Polymerase II, medicine.disease, polymerase proofreading–associated polyposis, Càncer d'endometri, Neoplasms::Neoplasms::Neoplastic Syndromes, Hereditary::Colorectal Neoplasms, Hereditary Nonpolyposis [DISEASES], Hereditary colorectal cancer, Mutation, hereditary colorectal cancer, neoplasias::neoplasias::síndromes neoplásicos hereditarios::neoplasias colorrectales hereditarias sin poliposis [ENFERMEDADES], exonuclease domain, Colorectal Neoplasms, Genetic diseases
Abstract: [Purpose]: Germline pathogenic variants in the exonuclease domain (ED) of polymerases POLE and POLD1 predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence of POLE and POLD1 variants in hereditary cancer are evaluated in this study. [Methods]: POLE and POLD1 were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics). Cosegregation and case–control studies, yeast-based functional assays, and tumor mutational analyses were performed for variant interpretation. [Results]: Twelve ED missense variants, 6 loss-of-function, and 23 outside-ED predicted-deleterious missense variants, all with population allele frequencies, This work was funded by the Spanish Ministry of Science and Innovation, cofunded by FEDER funds (SAF2016-80888-R, SAF2015-68016-R, Severo Ochoa SVP-2014-068895 contract [L.M.-P.]); Instituto de Salud Carlos III (PI16/00563, PI16/00588, PI14/00613, PI19/00553, CIBERONC CB16/12/00234, CIBERESP, Sara Borrell contract [P.M.]); Government of Catalonia [AGAUR 2017SGR1282, CERCA Program]; and Fundación Olga Torres. This study was facilitated by COST Action CA17118, supported by COST (European Cooperation in Science and Technology).
Published: 2020

30. Upper Pleistocene equids from Terrasses de la Riera dels Canyars (NE Iberian Peninsula): The presence of Equus ferus and Equus hydruntinus based on dental criteria and their implications for palaeontological identification and palaeoenvironmental reconstruction

Author: Montserrat Sanz, Alicia Sanz-Royo, and Joan Daura
Subjects: 010506 paleontology, geography.geographical_feature_category, biology, Dentition, Pleistocene, 010502 geochemistry & geophysics, biology.organism_classification, 01 natural sciences, Equus, Archaeology, Protocone, law.invention, Geography, law, Peninsula, Stadial, Radiocarbon dating, Hypocone, 0105 earth and related environmental sciences, Earth-Surface Processes
Abstract: The evolution and co-occurrence of equids in Europe during the Upper Pleistocene (125–10 ka) is a research line that has generated much debate owing to the difficulties in distinguishing between species. Here, we present a study of the dental remains of equids, dated by radiocarbon at ~34.6 (~39.6 cal) ka BP, from Terrasses de la Riera dels Canyars (Barcelona, NE Iberian Peninsula), a site where numerous remains of Equus hydruntinus and Equus ferus have been identified. Our observations indicate that combining measurements and morphological features, as opposed to their separate application, is useful for identifying Pleistocene equids at the species level. We identify seven morphological features to distinguish between the two species: four on the upper teeth – i) the shape of the protocone; ii) the presence/absence of a pli caballine; iii) the presence/absence of grooves in the styles; and, iv) the shape of the hypocone – and three on the lower dentition – v) the shape of the entoflexid; vi) the depth of the ectoflexid; and, vii) the presence/absence of the pticostylid fold. The identification of E. hydruntinus by dentition at the site reinforces evidence for the presence of these small equids during the Heinrich Stadial 4 in the Iberian Peninsula. The multi-proxy data (including phytoliths, charcoal, pollen, tooth wear, small and large mammals) obtained at Canyars suggest that E. hydruntinus of the NE Iberian Peninsula inhabited steppe-dominated landscapes with a Mediterranean component, indicating a less rigorous climate than that of more northern latitudes.
Published: 2020

31. Upstream migration of anadromous and potamodromous brown trout: patterns and triggers in a 25-year overview

Author: Juan Francisco Fuentes-Pérez, Ana García-Vega, José Ardaiz Ganuza, Francisco Javier Sanz-Ronda, and Pedro M. Leunda Urretabizkaia
Subjects: Fish migration, Upstream (petroleum industry), Fishery, Brown trout, 31 Ciencias Agrarias, Salmo trutta, Sea trout, Riverine trout, Aquatic Science, Biology
Abstract: Producción Científica, River fragmentation and alterations in flow and thermal regimes are the main stressors affecting migrating fish, which could be aggravated by climate change and increasing water demand. To assess these impacts and define mitigation measures, it is vital to understand fish movement patterns and the environmental variables affecting them. This study presents a long-term (1995–2019) analysis of upstream migration patterns of anadromous and potamodromous brown trout in the lower River Bidasoa (Spain). For this, captures in a monitoring station were analyzed using Survival Analysis and Random Forest techniques. Results showed that most upstream movements of potamodromous trout occurred in October–December, whereas in June–July for anadromous trout, although with differences regarding sex and size. Both, fish numbers and dates varied over time and were related to the environmental conditions, with different influence on each ecotype. The information provided from comparative studies can be used as a basis to develop adaptive management strategies to ensure freshwater species conservation. Moreover, studies in the southern distribution range can be crucial under climate warming scenarios, where species are expected to shift coldwards., Proyecto de innovación docente de la Universidad de Valladolid (PIF-UVa 2017), Ministerio de Ciencia, Innovación y Universidades (grant PTQ2018-010162), Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE
Published: 2021

32. Evolution under low antibiotic concentrations: a risk for the selection of Pseudomonas aeruginosa multidrug‐resistant mutants in nature

Author: José L. Martínez, Sara Hernando-Amado, and Fernando Sanz-García
Subjects: Drug, Imipenem, Pseudomonas aeruginosa, medicine.drug_class, media_common.quotation_subject, Antibiotics, Drug Resistance, Microbial, Microbial Sensitivity Tests, Biology, medicine.disease_cause, Microbiology, Anti-Bacterial Agents, Multiple drug resistance, Antibiotic resistance, medicine, Efflux, Ecosystem, Ecology, Evolution, Behavior and Systematics, Polymyxin B, media_common, medicine.drug
Abstract: Antibiotic pollution of non-clinical environments might have a relevant impact on human health if resistant pathogens are selected. However, this potential risk is often overlooked, since drug concentrations in nature are usually below their minimal inhibitory concentrations (MICs). Albeit, antibiotic resistant bacteria can be selected even at sub-MIC concentrations, in a range known as the sub-MIC selective window. Using short-term evolution experiments, we have determined the sub-MIC selective windows of the opportunistic pathogen Pseudomonas aeruginosa for seven antibiotics of clinical relevance, finding the ones of quinolones to be the widest, and the ones of polymyxin B and imipenem, the narrowest. Clinically relevant multidrug-resistant mutants arose within the sub-MIC selective windows of most antibiotics tested, being some of these phenotypes mediated by efflux pumps' activity. The fact that the concentration of antibiotics reported in aquatic ecosystems - colonizable by P. aeruginosa - are, in occasions, higher than the ones that select multidrug-resistant mutants in our assays, has implications for understanding the role of different ecosystems and conditions in the emergence of antibiotic resistance from a One-Health perspective. Further, it reinforces the importance of procuring accurate information on the sub-MIC selective windows for drugs of clinical value in pathogens with environmental niches.
Published: 2021

33. <scp>Three‐dimensional</scp> form and function of the nasal cavity and nasopharynx in humans and chimpanzees

Author: Markus Bastir, Manuel A. Burgos, and Daniel Sanz-Prieto
Subjects: Adult, Nasal cavity, Histology, Pan troglodytes, Comparative functional anatomy, Nose, Biology, Form and function, Nasopharynx, Airways, medicine, Animals, Humans, Computer Simulation, Craniofacial, Ecology, Evolution, Behavior and Systematics, Morphometrics, Computational fluid mechanics, Evolutionary transitions, 3D geometric morphometrics, medicine.anatomical_structure, Human evolution, Evolutionary biology, Homo sapiens, Hydrodynamics, Nasal Cavity, Anatomy, Adaptation, Biotechnology
Abstract: The facial differences between recent Pan troglodytes and Homo sapiens can be used as a proxy for the reduction of facial prognathism that happened during evolutionary transition between Australopithecines and early Homo. The projecting nasal morphology of Homo has been considered both a passive consequence of anatomical reorganization related to brain and integrated craniofacial evolution as well as an adaptation related to air-conditioning during physiological and behavioral shifts in human evolution. Yet, previous research suggested impaired air-conditioning in Homo challenging respiratory adaptations based on computational fluid dynamics (CFD) and airflow simulations. Here we improved CFD model at the inflow region and also carried out three-dimensional (3D) geometric morphometrics to address the hypothesis of impaired air-conditioning in humans and species differences in airway shape. With the new CFD model we simulated pressure, velocity, and temperature changes in airflow of six adult humans and six chimpanzees and analyzed 164 semi-landmarks of 10 humans and 10 chimpanzees for 3D size and shape comparisons. Our finding shows significantly different internal 3D nasal airways. Also, species means of pressure, velocity, and temperature differed statistically significantly. However, form-related differences in temperature exchanges seem subtle and may question adaptive disadvantages. We rather support a hypothesis of craniofacial changes in the Australopithecus-Homo transition that are related to brain evolution and craniofacial integration with facial and nasal modifications that contribute to maintain respiratory adaptations related to air conditioning., This work is supported by the Ministerio de Ciencia e Innovacion of Spain (Grant No. PID2019-105097RB-I00/AEI/10.13039/501100011033; and PID2020-115854GB-I00).
Published: 2021

34. Population genetics meets phylogenetics: new insights into the relationships among members of the genus Euthynnus (family Scombridae)

Author: Fambaye Ngom Sow, Genoveva Cerdenares, Thuy Yen Duong, Ghailen Hajjej, N’guessan Constance Diaha, Laura Vilà-Valls, Rosa M. Araguas, Nuria Sanz, Jordi Viñas, Rubén Muñoz-Lechuga, Jaime Alvarado-Bremer, Pedro G. Lino, and Judith Ollé
Subjects: mtDNA control region, education.field_of_study, Species complex, Euthynnus, biology, Scombridae, Population, Allopatric speciation, Zoology, Aquatic Science, biology.organism_classification, Genetic divergence, Phylogeography, education
Abstract: Euthynnus (family Scombridae) is a genus of marine pelagic fish species with a worldwide distribution that comprises three allopatric species: E. alletteratus, E. affinis and E. lineatus. All of them targeted by artisanal and commercial fisheries. We analyzed 263 individuals from Atlantic and Pacific Oceans using two genetic markers, the mtDNA Control Region (350 bp) and nuclear calmodulin (341 bp). The results obtained challenge the phylogeny of this group. We found a deep genetic divergence, probably at species level, within E. alletteratus, between the North Atlantic-Mediterranean and the Tropical East Atlantic. This deep genetic divergence was tested with several species delimitation methods. This complete phylogeographic association between the North Atlantic and the Tropical East Atlantic support the hypothesis of two cryptic species. In addition, population genetic heterogeneity was detected between the North East Atlantic–Mediterranean and North West Atlantic regions. Our results indicate two scales of differentiation in what is currently considered a single population. Accordingly, for management purposes, the populations of E. alletteratus, should be divided into a minimum of three management units. On the other hand, the high level of differentiation found in E. alletteratus contrasts with the shallow genetic divergence of E. affinis and E. lineatus.
Published: 2021

35. SARS-CoV-2 variants, a still unfinished story☆

Author: J.C. Sanz Moreno and M. Pérez-Abeledo
Subjects: Genetics, Whole genome sequencing, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Mutant, Variants, General Medicine, Review Article, Variantes, Biology, Genome, Vaccination, Antigen, biology.protein, Antibody, Gene
Abstract: Mutations in the SARS-CoV-2 genome can affect the gene encoding the Spike (S) antigen, which interacts with the host cell specific receptor, selecting mutant variants with changes in their infective capacity, pathogenic potential and resistance to neutralizing antibodies. The nomenclature to design the variants uses a colloquial form referred to the country or place of detection, a code from the “Pangolin” database and one from the “Nextstrain” page. New variants that have spread include the British B.1.1.7 (20I/501Y.V1), the South African B.1.351 (20H/501.V2), the Brazilian P.1 (20J/501Y.V3), the Californians B.1.427 B.1.429 (20C/S:452R) and the most recent, the Indian B.1.617 (VUI-21APR-01). The gold standard for the identification of the variants is whole genome sequencing. However, real-time PCR techniques have already been developed for the detection of specific mutations that can facilitate their presumptive identification. The impact of these variants on global vaccination programs has raised concern. It is generally thought that, since the response evoked by the vaccine against the S antigen is directed at the entire protein and the mutations only affect specific regions, the escape effect of the vaccine antibodies will be limited. Among the future strategies proposed for immuno-protection, the increase in the number of doses, the alternation of vaccines and the development of specific vaccines against different variants has been suggested.
Published: 2021

36. A higher incidence of moult–breeding overlap in great tits across time is linked to an increased frequency of second clutches: a possible effect of global warming?

Author: J.J. Sanz, Emilio Barba Campos, L. Imba, Iris Solís, Elena Álvarez, Ministerio de Ciencia e Innovación (España), and Ministerio de Economía y Competitividad (España)
Subjects: Great tit, España, Population, Zoology, Post–breeding moult, Effects of global warming, Parus major, Seasonal breeder, Cambio climático, Climate change, Clutch, education, Nature and Landscape Conservation, Parus, education.field_of_study, Cambios fenológicos, biology, Incidence (epidemiology), Global warming, Muda post–nupcial, biology.organism_classification, Phenological changes, QL1-991, Spain, Carbonero común, Animal Science and Zoology, Moulting
Abstract: The rise of temperatures due to global warming is related to a lengthening of the breeding season in many bird species. This allows more pairs to attempt two clutches within the breeding season, thus finishing their breeding activity later in the season and therefore potentially overlapping these with post–breeding moult. We tested whether this occurred in two Spanish great tit Parus major populations. The proportion of pairs laying second clutches increased from 1 % to 32 % over the study period in one of the populations (Sagunto, 1995–2019), while it did not change in the other (Quintos, 2006–2019; mean 5 %). We did not find any temporal trend for moult start date of late–breeding birds in any population. The proportion of individuals of both sexes that overlapped moult and breeding increased in Sagunto. For this latter population, sex and age, but not clutch type, contributed to the variability in the probability of overlapping in late–breeding individuals, this being higher for first–year males and lower for older females., El incremento del solapamiento entre la muda y la reproducción en el carbonero común está ligado a un aumento en la frecuencia de segundas puestas: ¿Un posible efecto del calentamiento global? El ascenso de las temperaturas debido al cambio climático está relacionado con un aumento de la duración de la temporada reproductiva de muchas especies de aves. Esto permite que más parejas intenten poner dos puestas durante la temporada reproductiva y conlleva que terminen sus actividades reproductivas más tarde; por tanto, estas actividades se podrían solapar con la muda postnupcial. Hemos comprobado si esto ocurre en dos poblaciones de carbonero común (Parus major) de España. La proporción de parejas con segundas puestas se ha incrementado del 1 % al 32 % durante el periodo de estudio en una de las poblaciones (Sagunto, 1995–2019), mientras que en la otra no ha cambiado (Quintos, 2006–2019; media 5 %). No hemos encontrado ninguna tendencia temporal en cuanto a la fecha de inicio de muda de los individuos que están criando en fechas tardías en ninguna de las dos poblaciones. La proporción de individuos de ambos sexos cuya muda y actividad reproductiva se solaparon se ha incrementado en Sagunto. En esta última población, el sexo y la edad, pero no el tipo de puesta, contribuyeron a explicar la variabilidad en la probabilidad de solapamiento entre los reproductores tardíos, ya que esta es mayor en los machos de primer año y menor en hembras adultas., This study was partially supported by the projects CGL2013–48001–C2–1–P (Spanish Ministry of Science and Innovation) and CGL2016–79568–C3–1–P (Spanish Ministry of Economy and Competitiveness) thanks to the European Social Fund.
Published: 2021

37. Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only

Author: Mélanie Gressette, Eric Jacquet, Marta Novotova, Vladimir Veksler, Mathias Mericskay, Kaveen Bedouet, Audrey Solgadi, Ahmed Karoui, Maria-Nieves Sanz, Anne Garnier, Renée Ventura-Clapier, Lucile Grimbert, Catherine Rucker-Martin, Christophe Lemaire, Susana Gomez, Jérôme Piquereau, Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), Slovak Academy of Sciences (SAS), Institut Paris Saclay d’Innovation Thérapeutique (IPSIT), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), JACQUET, ERIC, Metabolic therapy of heart failure: which place for a cocktail of B vitamins? - - HF-MetaB2019 - ANR-19-ECVD-0007 - ERA-CVD - VALID, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), This study was supported by the Slovak Research and Development Agency grant (M.N., APVV-15-0302), and by the Slovak Scientific Grant Agency (M.N., VEGA 2/0091/19). R.V.-C is emeritus scientist at CNRS., and ANR-19-ECVD-0007,HF-MetaB,Metabolic therapy of heart failure: which place for a cocktail of B vitamins?(2019)
Subjects: Male, Cardiac function curve, medicine.medical_specialty, Heart Diseases, Cardiac fibrosis, Cardiolipins, Physiology, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Gender Studies, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, AMP-activated protein kinase, Fibrosis, Internal medicine, medicine, Cardiolipin, Animals, QP1-981, Protein kinase A, 030304 developmental biology, Mice, Knockout, 0303 health sciences, biology, business.industry, Research, AMPK, Heart, Energy metabolism, medicine.disease, Mitochondria, [SDV] Life Sciences [q-bio], chemistry, Heart failure, biology.protein, cardiovascular system, Medicine, Female, business
Abstract: Background The AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects. Methods To decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice. This allowed us to avoid the eventual impact of AMPK-KO in peripheral organs. Results Cardio-specific Ampkα2 deficiency led to a progressive left ventricular systolic dysfunction and the development of cardiac fibrosis in males. We observed a reduction in complex I-driven respiration without change in mitochondrial mass or in vitro complex I activity, associated with a rearrangement of the cardiolipins and reduced integration of complex I into the electron transport chain supercomplexes. Strikingly, none of these defects were present in females. Interestingly, suppression of estradiol signaling by ovariectomy partially mimicked the male sensitivity to AMPK loss, notably the cardiac fibrosis and the rearrangement of cardiolipins, but not the cardiac function that remained protected. Conclusion Our results confirm the close link between AMPK and cardiac mitochondrial function, but also highlight links with cardiac fibrosis. Importantly, we show that AMPK is differently involved in these processes in males and females, which may have clinical implications for the use of AMPK activators in the treatment of heart failure., Highlights AMPK is a metabolic sensor of cellular energy which regulates energy homeostasis.We generated a cardiac-specific inducible deletion of Ampkα2 and demonstrated that this deletion induces mild cardiac dysfunction in male only.Cardiac dysfunction observed in males was associated with cardiac fibrosis and cardiac cardiolipin remodeling that are not seen in females.Although no significant cardiac function alteration was noticed in ovariectomized female Ampkα2ciKO mice, these latter exhibited cardiac fibrosis and mild cardiolipins remodeling.Our results show a higher dependence on AMPK signaling fibrosis and cardiolipin biosynthesis/maturation in males, either due to the absence of female hormones protection or/and to the action of male hormones. This may contribute to the known difference in cardiovascular risk and outcome between sexes.
Published: 2021

38. Periodontitis and rheumatoid arthritis: What have we learned about their connection and their treatment?

Author: Mariano Sanz and Jerián González-Febles
Subjects: Periodontitis, biology, business.industry, Autoantibody, Aggregatibacter actinomycetemcomitans, Anti–citrullinated protein antibody, Citrullination, medicine.disease, biology.organism_classification, Arthritis, Rheumatoid, Rheumatoid arthritis, Immunology, medicine, biology.protein, Humans, Periodontics, Rheumatoid factor, business, Porphyromonas gingivalis
Abstract: Rheumatoid arthritis and periodontitis are chronic inflammatory diseases defined respectively by the destruction of the articular cartilage and tooth-supporting periodontal tissues. Although the epidemiologic evidence for an association between these two diseases is still scarce, there is emerging scientific information linking specific bacterial periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, in the citrullination process, leading to autoantibody formation and compromised immunotolerance of the susceptible patient to rheumatoid arthritis. In this review, we update the existing information on the evidence, not only regarding the epidemiologic association, but also the biologic mechanisms linking these two diseases. Finally, we review information emerging from intervention studies evaluating whether periodontal treatment could influence the initiation and progression of rheumatoid arthritis.
Published: 2021

39. Correlation between PD-L1 expression and MET gene amplification in patients with advanced non-small-cell lung cancer and no other actionable oncogenic driver

Author: Ana M Muñoz Marmol, Marta Domenech, Marc Cucurull, Maria Saigi, Carolina Sanz, Anna Martínez-Cardús, Ainhoa Hernández, Teresa Moran, Alba Hernandez-Gallego, Enric Carcereny, Anna Estival, Aintzane Urbizu, Adrià Bernat, and Jose Luis Mate
Subjects: PD-L1, Oncology, medicine.medical_specialty, Lung, biology, business.industry, Cell, smoking habit, Retrospective cohort study, oncogenic driver, medicine.disease, Correlation, medicine.anatomical_structure, Internal medicine, ROS1, biology.protein, Medicine, In patient, business, Lung cancer, non-small cell lung cancer, MET amplification, Research Paper
Abstract: Non-small cell lung cancers (NSCLC) are the most common type of lung cancer and can be classified according to the presence of mutually exclusive oncogenic drivers. The majority of NSCLC patients present a non-actionable oncogenic driver, and treatment resistance through the amplification of the MET proto-oncogene (MET) or the expression of programmed cell death protein 1 ligand (PD-L1) is common. Herein, we investigated the relation between MET gene amplification and PD-L1 expression in patients with advanced NSCLC and no other actionable oncogenic driver (i.e., EGFR, ALK, ROS1). Our retrospective observational study analyzed data from 48 patients (78% men, median age 66 years) admitted to the Germans Trias i Pujol Hospital, Spain, between July 2015 and February 2019. Patients presenting MET amplification showed a higher proportion of PD-L1 expression (93% vs. 39%; p < 0.001) and overexpression (64% vs. 27%; p = 0.020) than those with non-amplified MET. PD-L1 expression was not significantly different when analyzed by sex (p = 0.624), smoking history (p = 0.429), and Eastern Cooperative Oncology Group Performance Status (p = 0.597) Overall survival rates were not significantly affected by MET amplification (high and intermediate amplification vs low amplification and non-amplificated) (p = 0.252) nor PD-L1 expression (> vs =< 50%) (p = 0.893). In conclusion, a positive correlation was found between MET gene amplification and PD-L1 expression and highly expressed (above 50%) in patients with NSCLC and no other actionable oncogenic driver. It could be translated as new guided-treatment oportunities for these patients.
Published: 2021

40. Management of mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a kidney recipient: a case report

Author: A Rodríguez-Campón, G Tabernero, P Fraile, Francisco Boix, María C. Chillón, Ramón García-Sanz, S García-Sánchez, J Feito, and Junta de Castilla y León
Subjects: Donor specific antibodies, Microbiology (medical), T-cell mediated rejection, Transplant recipient, Clinical Biochemistry, Immunology, Desensitization, Human leukocyte antigen, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Rescue therapy, medicine, Immunology and Allergy, Cytotoxic T cell, Mixed acute rejection, 0303 health sciences, Kidney, biology, medicine.diagnostic_test, 030306 microbiology, business.industry, Biochemistry (medical), HLA, surgical procedures, operative, Infectious Diseases, medicine.anatomical_structure, Antibody-mediated rejection, 030220 oncology & carcinogenesis, biology.protein, Complement binding, Renal biopsy, Antibody, business, CD8
Abstract: Mixed acute rejection is a clinicopathological entity that is difficult to accurately diagnose, and so may be under-reported. Allografts are lost more often than in either humoral or cellular rejection. The diagnosis requires both histological and immunological studies on renal biopsy and blood specimens from the transplant recipient to provide the required rescue therapy to abolish the allogeneic response against the graft. We present a clinical case report of an active mixed acute rejection driven by a de novo donor-specific complement-binding anti-DQB1*03:01 antibody and intraepithelial CD8 T-cells in a patient with a kidney transplant. The patient was diagnosed, treated, and followed up as per the local institution’s procedure with a full recovery of graft function. Our case emphasises the challenge of a mixed acute rejection and supports the need to improve the post-transplant outcome of recipients and their grafts., This work was partially funded by the Gerencia Regional de Salud (GRS) of Castilla y León [GRS 2080/A/19].
Published: 2021

41. Grape Stalk-Based Extracts Controlling Fruit Pathogenic Fungi as a Waste Biomass Valorization Alternative in Winemaking

Author: Martín A. Palazzolo, Marcela Kurina-Sanz, Antares A. Martinez, and Maximiliano Martín Aballay
Subjects: Environmental Engineering, biology, Renewable Energy, Sustainability and the Environment, Ethyl acetate, Biomass, biology.organism_classification, Penicillium chrysogenum, Aspergillus candidus, chemistry.chemical_compound, Horticulture, chemistry, Rhizopus, Raceme, Cultivar, Waste Management and Disposal, Winemaking
Abstract: Grape stalks—the lignocellulosic skeleton of the grape raceme- are accumulated in massive piles immediately after harvest and become a concentrated pollutant. Fungi cause several rots in grapevine and other fruit cultivars and albeit biocontrol agents are available, superior technologies must be developed to rival synthetic counterparts. In this work, we describe the preparation of grape stalk lipophilic extracts from Malbec, Cabernet sauvignon, Chardonnay and Pedro Gimenez as biocontrol tools against Aspergillus candidus, Penicillium chrysogenum, and Rhizopus sp., which are pathogenic for grapes and other fruits. Grape stalk extracts were obtained with hexane, diethyl ether, ethyl acetate, and ethanol. Yields were in the range of 1 to 23% w / w according to solvent polarity. Extracts were separated into lipophilic sub-extracts—yields varied from 70 up to 12% w /w due to solvent polarity. Sub-extracts were assayed for antifungal activity in vitro and the one obtained from Pedro Gimenez with ethanol exhibited the broadest biocontrol spectrum at 2.5 × 104 mg/L. This sub-extract was separated into components by column chromatography to inquire further on its biocontrol activity. A bioactivity-guided test against Rhizopus sp. revealed that this effect relies on gamma-sitosterol and a biocontrol cut-off value of 5.1 × 103 mg/L was estimated.
Published: 2021

42. Author Correction: Penultimate deglacial warming across the Mediterranean Sea revealed by clumped isotopes in foraminifera

Author: Stefano M. Bernasconi, Eelco J. Rohling, Alvaro Fernandez, David Heslop, Katharine M. Grant, Laura Rodríguez-Sanz, Giuseppe Marino, and Inigo A. Müller
Subjects: Foraminifera, Multidisciplinary, Oceanography, Mediterranean sea, biology, Isotope, Science, Medicine, biology.organism_classification, Geology
Published: 2021

43. Culture Medium and Sex Drive Epigenetic Reprogramming in Preimplantation Bovine Embryos

Author: Pilar Coy, Fernando Perez-Sanz, Sebastian Canovas, Elena Ivanova, Gavin Kelsey, Meriem Hamdi, Dimitrios Rizos, Fundación Séneca, Ministerio de Ciencia e Innovación (España), Biotechnology and Biological Sciences Research Council (UK), Medical Research Council (UK), Sebastian Canovas, Meriem Hamdi, Fernando Perez-Sanz, Dimitrios Rizos, Gavin Kelsey, Pilar Coy, Sebastian Canovas [0000-0003-4190-6258], Meriem Hamdi [0000-0002-2792-8293], Fernando Perez-Sanz [0000-0002-8143-7794], Dimitrios Rizos [0000-0001-6813-3940], Gavin Kelsey [0000-0002-9762-5634], Pilar Coy [0000-0002-3943-1890], Perez-Sanz, Fernando [0000-0002-8143-7794], Rizos, Dimitrios [0000-0001-6813-3940], Kelsey, Gavin [0000-0002-9762-5634], Coy, Pilar [0000-0002-3943-1890], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, Reproductive technology, Epigenesis, Genetic, 0302 clinical medicine, Blood serum, Biology (General), Spectroscopy, Principal Component Analysis, Sex Characteristics, 030219 obstetrics & reproductive medicine, DNA methylation, Epigenetic, Embryo, General Medicine, Methylation, Bovine, Cellular Reprogramming, Computer Science Applications, Chemistry, medicine.anatomical_structure, embryonic structures, Female, Reprogramming, QH301-705.5, embryo, Fertilization in Vitro, Biology, Article, Catalysis, Inorganic Chemistry, Andrology, 03 medical and health sciences, Sexual dimorphism, medicine, Animals, Epigenetics, Blastocyst, Preimplantation, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Organic Chemistry, Molecular Sequence Annotation, Chromosomes, Mammalian, Culture Media, Gene Ontology, Logistic Models, 030104 developmental biology, Cattle, CpG Islands
Abstract: Departamento de Reproducción Animal (INIA), Assisted reproductive technologies impact transcriptome and epigenome of embryos and can result in long-term phenotypic consequences. Whole-genome DNA methylation profiles from individual bovine blastocysts in vivo- and in vitro-derived (using three sources of protein: reproductive fluids, blood serum and bovine serum albumin) were generated. The impact of in vitro culture on DNA methylation was analyzed, and sex-specific methylation differences at blastocyst stage were uncovered. In vivo embryos showed the highest levels of methylation (29.5%), close to those produced in vitro with serum, whilst embryos produced in vitro with reproductive fluids or albumin showed less global methylation (25–25.4%). During repetitive element analysis, the serum group was the most affected. DNA methylation differences between in vivo and in vitro groups were more frequent in the first intron than in CpGi in promoters. Moreover, hierarchical cluster analysis showed that sex produced a stronger bias in the results than embryo origin. For each group, distance between male and female embryos varied, with in vivo blastocyst showing a lesser distance. Between the sexually dimorphic methylated tiles, which were biased to X-chromosome, critical factors for reproduction, developmental process, cell proliferation and DNA methylation machinery were included. These results support the idea that blastocysts show sexually-dimorphic DNA methylation patterns, and the known picture about the blastocyst methylome should be reconsidered, This research was funded by Fundación Seneca-Región de Murcia (Spain), grant number 20040/GERM/16, by the Ministry of Science and Innovation (Spain), grant numbers AGL2015–66341-R, AGL-2015-70140-R, PID2019-111641RB-I00 and by the UK Biotechnology and Biological Sciences Research Council and Medical Research Council., This article belongs to the Special Issue Mammalian Gametes: Molecular Traits Shaping Their Form and Fate
Published: 2021

44. In vitro activity of delafloxacin against highly levofloxacin-resistant invasive isolates of Streptococcus pneumoniae

Author: Alejandro Cobos, Cristina Loras, Juan Carlos Sanz, and Emilia Cercenado
Subjects: 0301 basic medicine, Microbiology (medical), Cefotaxime, Topoisomerase IV, 030106 microbiology, Erythromycin, Levofloxacin, medicine.disease_cause, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Streptococcus pneumoniae, medicine, 030212 general & internal medicine, biology, biochemical phenomena, metabolism, and nutrition, Anti-Bacterial Agents, Penicillin, chemistry, biology.protein, Delafloxacin, Quellung reaction, Fluoroquinolones, medicine.drug
Abstract: Introduction We report the activity of delafloxacin, a new fluoroquinolone with high affinity for both topoisomerase IV and DNA gyrase, against highly-levofloxacin-resistant invasive strains of Streptococcus pneumoniae. Methods A total of 173 highly-levofloxacin-resistant (MIC >32 mg/L) S. pneumoniae invasive isolates were studied. The strains were isolated from blood (n = 162) and other sterile fluids (n = 11). Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin MICs were determined by the gradient diffusion method following EUCAST guidelines and breakpoints. Results Among the isolates, 32.9% were penicillin non-susceptible, 19.7% cefotaxime non-susceptible, and 76.9% erythromycin resistant. All were susceptible to vancomycin. Delafloxacin MIC50 and MIC90 (mg/L) values were 0.064 and 0.12, respectively; 60% (15/25) of serotype 9V isolates showed delafloxacin MICs ≥ 0.12 mg/L. Conclusions Delafloxacin was very active against highly-levofloxacin-resistant invasive isolates of S. pneumoniae. Isolates belonging to serotype 9V showed higher delafloxacin MIC values.
Published: 2022

45. Ophthalmia nodosa due to the pine processionary caterpillar: Report of three cases and review of the literature

Author: J. González-Martín-Moro, Rosario Cobo-Soriano, P Moreno-Martín, C. Izquierdo-Rodríguez, E. Dorronzoro-Ramírez, and F Gómez-Sanz
Subjects: Ophthalmology, 2019-20 coronavirus outbreak, Ophthalmia nodosa, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pine processionary caterpillar, medicine, Biology, medicine.disease, Virology
Published: 2022

46. Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping

Author: A Antela, Coral García Vallecillos, Leopoldo Muñoz Moreno, Fernando Montolio, Hortensia Álvarez, M Casadellà, Irene Portilla, Bibiana Planas, Félix Gutiérrez, Daniel Podzamczer, Sergio Padilla, R Paredes, Arkaitz Imaz, María Pilar Carmona, Maria Casadellà, Alfredo Rodríguez, M Montero-Alonso, Xabier Kortajarena, Isabel Bravo, M Masiá, Adria Curran, J Navarro, Antonio Ocampo, P Carmona-Oyaga, Vicente Boix, Marc Noguera-Julian, M Noguera-Julian, J R Santos, L Pérez-Martínez, J Sanz, Josean A Iribarren, Jordi Navarro, M J Vivancos, Anna Chamorro, Maialen Ibarguren, Celia Miralles, Juan José Ramos González, José Hernández Quero, Esperanza Merino, Cristina Miranda, A Imaz, Pilar Barrufet, Jèssica Muñoz Rodríguez, N Valcarce-Pardeiro, Maria Gracia Mateo, Lluís Force, Ángela Gutiérrez Liarte, A Ocampo, L Muñoz-Medina, Joaquín Portilla, José Ramón Blanco, Livia Giner, P Domingo, P Barrufet, Ana Mariño, Laura Pérez-Martínez, J Pasquau, Diego Torrús, María del, José R. Santos, Araceli Adsuar, Santiago Moreno, Ana Gómez Berrocal, Ariadna Torrella, Jesús Sanz, Melissa Carreres, Nieves Valcarce Pardeiro, Juan Pasquau, Hernando Knobel, Mar Masiá, Marta Montero-Alonso, J Villar-García, Sergio Reus, Catalina Robledano, J Portilla, Rafael Micán, Judit Villar-García, Antonio Antela, R Micán-Rivera, Pere Domingo, María J Pérez-Elías, Roger Paredes, Fernando Dronda, María Jesús Vivancos, Mar Gutierrez, and Marcos Diez
Subjects: Microbiology (medical), Genotype, Population, Integrase inhibitor, HIV Infections, HIV Integrase, Drug resistance, Virus, Cohort Studies, Drug Resistance, Viral, Humans, Medicine, Pharmacology (medical), Protease inhibitor (pharmacology), HIV Integrase Inhibitors, Prospective Studies, education, Genotyping, Pharmacology, education.field_of_study, Integrases, biology, business.industry, Virology, Reverse transcriptase, Integrase, Infectious Diseases, Spain, Mutation, HIV-1, biology.protein, business
Abstract: BackgroundTransmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted.ObjectivesWe evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016.MethodsPre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%–19% of the virus population were considered to be low-frequency variants.ResultsFrom a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants.ConclusionsTransmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.
Published: 2020

47. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author: Lara Gibellini, Sussan Nourshargh, Susanna Cardell, Wlodzimierz Maslinski, Mar Felipo-Benavent, Florian Mair, Hans-Martin Jäck, Lilly Lopez, Klaus Warnatz, John Trowsdale, Diana Ordonez, Marcus Eich, William Hwang, Anne Cooke, Dirk Mielenz, Alberto Orfao, Winfried F. Pickl, Vladimir Benes, Alice Yue, T. Vincent Shankey, Maria Tsoumakidou, Virginia Litwin, Gelo Victoriano Dela Cruz, Andrea Cavani, Sara De Biasi, Larissa Nogueira Almeida, Jonathan J M Landry, Claudia Haftmann, Charlotte Esser, Ana Cumano, Anneke Wilharm, Francesco Dieli, Rudi Beyaert, Alessio Mazzoni, Burkhard Ludewig, Carlo Pucillo, Dirk H. Busch, Joe Trotter, Stipan Jonjić, Marc Veldhoen, Josef Spidlen, Aja M. Rieger, Dieter Adam, Srijit Khan, Todd A. Fehniger, Giuseppe Matarese, Maximilien Evrard, Christian Maueröder, Steffen Schmitt, Kristin A. Hogquist, Barry Moran, Raghavendra Palankar, Markus Feuerer, S Schmid, Susann Rahmig, Amy E. Lovett-Racke, James V. Watson, Megan K. Levings, Susanne Melzer, Dinko Pavlinic, Christopher M. Harpur, Christina Stehle, A. Graham Pockley, Toshinori Nakayama, Attila Tárnok, Juhao Yang, Michael Lohoff, Paulo Vieira, Francisco Sala-de-Oyanguren, Christian Kurts, Anastasia Gangaev, Alfonso Blanco, Hans Scherer, Regine J. Dress, Bruno Silva-Santos, Kiyoshi Takeda, Bimba F. Hoyer, Ilenia Cammarata, Daryl Grummitt, Isabel Panse, Günnur Deniz, Bianka Baying, Friederike Ebner, Esther Schimisky, Leo Hansmann, Thomas Kamradt, Edwin van der Pol, Daniel Scott-Algara, Anna Iannone, Giorgia Alvisi, Sebastian R. Schulz, Francesco Liotta, Irmgard Förster, Beatriz Jávega, Hans-Peter Rahn, Caetano Reis e Sousa, Livius Penter, Xuetao Cao, David P. Sester, Keisuke Goda, Peter Wurst, Iain B. McInnes, Ricardo T. Gazzinelli, Federica Piancone, Gerald Willimsky, Yotam Raz, Pärt Peterson, Wolfgang Fritzsche, Yvonne Samstag, Martin Büscher, Thomas Schüler, Susanne Hartmann, Robert J. Wilkinson, Anna E. S. Brooks, Steven L. C. Ketelaars, Catherine Sautès-Fridman, Anna Rubartelli, Petra Bacher, Katja Kobow, Marco A. Cassatella, Andrea Hauser, Henrik E. Mei, Kilian Schober, Silvia Della Bella, Graham Anderson, Michael D. Ward, Garth Cameron, Sebastian Lunemann, Katharina Kriegsmann, Katarzyna M. Sitnik, Brice Gaudilliere, Chantip Dang-Heine, Marcello Pinti, Paul Klenerman, Frank A. Schildberg, Joana Barros-Martins, Laura G. Rico, Hanlin Zhang, Christian Münz, Thomas Dörner, Jakob Zimmermann, Andrea M. Cooper, Jonni S. Moore, Andreas Diefenbach, Yanling Liu, Wolfgang Bauer, Tobit Steinmetz, Katharina Pracht, Leonard Tan, Peter K. Jani, Alan M. Stall, Petra Hoffmann, Christine S. Falk, Jasmin Knopf, Simon Fillatreau, Hans-Dieter Volk, Luis E. Muñoz, David L. Haviland, William W. Agace, Jonathan Rebhahn, Ljiljana Cvetkovic, Mohamed Trebak, Jordi Petriz, Mario Clerici, Diether J. Recktenwald, Anders Ståhlberg, Tristan Holland, Helen M. McGuire, Sa A. Wang, Christian Kukat, Thomas Kroneis, Laura Cook, Wan Ting Kong, Xin M. Wang, Britta Engelhardt, Pierre Coulie, Genny Del Zotto, Sally A. Quataert, Kata Filkor, Gabriele Multhoff, Bartek Rajwa, Federica Calzetti, Hans Minderman, Cosima T. Baldari, Jens Geginat, Hervé Luche, Gert Van Isterdael, Linda Schadt, Sophia Urbanczyk, Giovanna Borsellino, Liping Yu, Dale I. Godfrey, Achille Anselmo, Rachael C. Walker, Andreas Grützkau, David W. Hedley, Birgit Sawitzki, Silvia Piconese, Maria Yazdanbakhsh, Burkhard Becher, Ramon Bellmas Sanz, Michael Delacher, Hyun-Dong Chang, Immanuel Andrä, Hans-Gustaf Ljunggren, José-Enrique O'Connor, Ahad Khalilnezhad, Sharon Sanderson, Federico Colombo, Götz R. A. Ehrhardt, Inga Sandrock, Enrico Lugli, Christian Bogdan, James B. Wing, Susann Müller, Tomohiro Kurosaki, Derek Davies, Ester B. M. Remmerswaal, Kylie M. Quinn, Christopher A. Hunter, Andreas Radbruch, Timothy P. Bushnell, Anna Erdei, Sabine Adam-Klages, Pascale Eede, Van Duc Dang, Rieke Winkelmann, Thomas Korn, Gemma A. Foulds, Dirk Baumjohann, Matthias Schiemann, Manfred Kopf, Jan Kisielow, Lisa Richter, Jochen Huehn, Gloria Martrus, Alexander Scheffold, Jessica G. Borger, Sidonia B G Eckle, John Bellamy Foster, Anna Katharina Simon, Alicia Wong, Mübeccel Akdis, Gisa Tiegs, Toralf Kaiser, James McCluskey, Anna Vittoria Mattioli, Aaron J. Marshall, Hui-Fern Koay, Eva Orlowski-Oliver, Anja E. Hauser, J. Paul Robinson, Jay K. Kolls, Luca Battistini, Mairi McGrath, Jane L. Grogan, Natalio Garbi, Timothy Tree, Kingston H. G. Mills, Stefan H. E. Kaufmann, Wolfgang Schuh, Ryan R. Brinkman, Tim R. Mosmann, Vincenzo Barnaba, Andreas Dolf, Lorenzo Cosmi, Bo Huang, Andreia C. Lino, Baerbel Keller, René A. W. van Lier, Alexandra J. Corbett, Paul S. Frenette, Pleun Hombrink, Helena Radbruch, Sofie Van Gassen, Olivier Lantz, Lorenzo Moretta, Désirée Kunkel, Kirsten A. Ward-Hartstonge, Armin Saalmüller, Leslie Y. T. Leung, Salvador Vento-Asturias, Paola Lanuti, Alicia Martínez-Romero, Sarah Warth, Zhiyong Poon, Diana Dudziak, Andrea Cossarizza, Kovit Pattanapanyasat, Konrad von Volkmann, Jessica P. Houston, Agnès Lehuen, Andrew Filby, Pratip K. Chattopadhyay, Stefano Casola, Annika Wiedemann, Hannes Stockinger, Jürgen Ruland, Arturo Zychlinsky, Claudia Waskow, Katrin Neumann, Ari Waisman, Lucienne Chatenoud, Sudipto Bari, Kamran Ghoreschi, David W. Galbraith, Yvan Saeys, Hamida Hammad, Andrea Gori, Miguel López-Botet, Gabriel Núñez, Sabine Ivison, Michael Hundemer, Dorothea Reimer, Mark C. Dessing, Günter J. Hämmerling, Rudolf A. Manz, Tomas Kalina, Jonas Hahn, Holden T. Maecker, Hendy Kristyanto, Martin S. Davey, Henning Ulrich, Michael L. Dustin, Takashi Saito, Yousuke Takahama, Milena Nasi, Johanna Huber, Jürgen Wienands, Paolo Dellabona, Andreas Schlitzer, Michael D. Leipold, Kerstin H. Mair, Christian Peth, Immo Prinz, Chiara Romagnani, José M. González-Navajas, Josephine Schlosser, Marina Saresella, Matthias Edinger, Dirk Brenner, Nicole Baumgarth, Rikard Holmdahl, Fang-Ping Huang, Guadalupe Herrera, Malte Paulsen, Gergely Toldi, Luka Cicin-Sain, Reiner Schulte, Christina E. Zielinski, Thomas Winkler, Christoph Goettlinger, Philip E. Boulais, Jennie H M Yang, Antonio Celada, Heike Kunze-Schumacher, Julia Tornack, Florian Ingelfinger, Jenny Mjösberg, Andy Riddell, Leonie Wegener, Thomas Höfer, Christoph Hess, James P. Di Santo, Anna E. Oja, J. Kühne, Willem van de Veen, Mary Bebawy, Alberto Mantovani, Bart Everts, Giovanna Lombardi, Laura Maggi, Anouk von Borstel, Pia Kvistborg, Elisabetta Traggiai, A Ochel, Nima Aghaeepour, Charles-Antoine Dutertre, Matthieu Allez, Thomas Höllt, Wenjun Ouyang, Regina Stark, Maries van den Broek, Shimon Sakaguchi, Paul K. Wallace, Silvano Sozzani, Francesca LaRosa, Annette Oxenius, Malgorzata J. Podolska, Ivana Marventano, Wilhelm Gerner, Oliver F. Wirz, Britta Frehse, Gevitha Ravichandran, Martin Herrmann, Carl S. Goodyear, Gary Warnes, Helen Ferry, Stefan Frischbutter, Tim R. Radstake, Salomé LeibundGut-Landmann, Yi Zhao, Axel Schulz, Angela Santoni, Pablo Engel, Daniela C. Hernández, Andreas Acs, Cristiano Scottà, Francesco Annunziato, Thomas Weisenburger, Wolfgang Beisker, Sue Chow, Fritz Melchers, Daniel E. Speiser, Immanuel Kwok, Florent Ginhoux, Dominic A. Boardman, Natalie Stanley, Carsten Watzl, Marie Follo, Erik Lubberts, Andreas Krueger, Susanne Ziegler, Göran K. Hansson, David Voehringer, Antonia Niedobitek, Eleni Christakou, Lai Guan Ng, Sabine Baumgart, Nicholas A Gherardin, Antonio Cosma, Orla Maguire, Jolene Bradford, Daniel Schraivogel, Linda Quatrini, Stephen D. Miller, Rheumatology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Institute of Clinical Molecular Biology, Kiel University, Department of Life Sciences [Siena, Italy], Università degli Studi di Siena = University of Siena (UNISI), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Dulbecco Telethon Institute/Department of Biology, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, European Molecular Biology Laboratory [Heidelberg] (EMBL), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Fondazione Santa Lucia (IRCCS), Department of Immunology, Chinese Academy of Medical Sciences, FIRC Institute of Molecular Oncology Foundation, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, Monash University [Clayton], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biopharmacy [Bruxelles, Belgium] (Institute for Medical Immunology IMI), Université libre de Bruxelles (ULB), Charité Hospital, Humboldt-Universität zu Berlin, Agency for science, technology and research [Singapore] (A*STAR), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], Kennedy Institute of Rheumatology [Oxford, UK], Imperial College London, Theodor Kocher Institute, University of Bern, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] ( IUF), Université Lumière - Lyon 2 (UL2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Edinburgh, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Universitat de Barcelona (UB), Rheumatologie, Cell Biology, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Delft University of Technology (TU Delft), Medical Inflammation Research, Karolinska Institutet [Stockholm], Department of Photonics Engineering [Lyngby], Technical University of Denmark [Lyngby] (DTU), Dpt of Experimental Immunology [Braunschweig], Helmholtz Centre for Infection Research (HZI), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Histology and Embryology, University of Rijeka, Freiburg University Medical Center, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Institute of Integrative Biology, Molecular Biomedicine, Berlin Institute of Health (BIH), Laboratory for Lymphocyte Differentiation, RIKEN Research Center, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Surgery [Vancouver, BC, Canada] (Child and Family Research Institute), University of British Columbia (UBC)-Child and Family Research Institute [Vancouver, BC, Canada], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, King‘s College London, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brustzentrum Kantonsspital St. Gallen, Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Heinrich Pette Institute [Hamburg], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Immunology and Cell Biology, Mario Negri Institute, Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation, Institute of Translational Medicine, Klinik für Dermatologie, Venerologie und Allergologie, School of Biochemistry and Immunology, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Centre de Recherche Publique- Santé, Université du Luxembourg (Uni.lu), William Harvey Research Institute, Barts and the London Medical School, University of Michigan [Ann Arbor], University of Michigan System, Centro de Investigacion del Cancer (CSIC), Universitario de Salamanca, Molecular Pathology [Tartu, Estonia], University of Tartu, Hannover Medical School [Hannover] (MHH), Centre d'Immunologie de Marseille - Luminy (CIML), Monash Biomedicine Discovery Institute, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Data Mining and Modelling for Biomedicine [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, RIKEN Research Center for Allergy and Immunology, Osaka University [Osaka], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institute of Medical Immunology [Berlin, Germany], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Otto-von-Guericke University [Magdeburg] (OVGU), SUPA School of Physics and Astronomy [University of St Andrews], University of St Andrews [Scotland]-Scottish Universities Physics Alliance (SUPA), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), General Pathology and Immunology (GPI), University of Brescia, Université de Lausanne (UNIL), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Dept. Pediatric Cardiology, Universität Leipzig [Leipzig], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Cardiovascular Sciences, Albany Medical College, Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), Department of Information Technology [Gent], Universiteit Gent, Department of Plant Systems Biology, Department of Plant Biotechnology and Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Division of Molecular Immunology, Institute for Immunology, Department of Geological Sciences, University of Oregon [Eugene], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Colorado [Colorado Springs] (UCCS), FACS laboratory, Cancer Research, London, Cancer Research UK, Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Barbara Davis Center for Childhood Diabetes (BDC), University of Colorado Anschutz [Aurora], School of Computer and Electronic Information [Guangxi University], Guangxi University [Nanning], School of Materials Science and Engineering, Nanyang Technological University [Singapour], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Work in the laboratory of Dieter Adam is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 125440785 – SFB 877, Project B2.Petra Hoffmann, Andrea Hauser, and Matthias Edinger thank BD Biosciences®, San José, CA, USA, and SKAN AG, Bale, Switzerland for fruitful cooperation during the development, construction, and installation of the GMP‐compliant cell sorting equipment and the Bavarian Immune Therapy Network (BayImmuNet) for financial support.Edwin van der Pol and Paola Lanuti acknowledge Aleksandra Gąsecka M.D. for excellent experimental support and Dr. Rienk Nieuwland for textual suggestions. This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO‐TTW), research program VENI 15924.Jessica G Borger, Kylie M Quinn, Mairi McGrath, and Regina Stark thank Francesco Siracusa and Patrick Maschmeyer for providing data.Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14‐1. Rudolf A. Manz was supported by the Excellence Cluster 'Inflammation at Interfaces' (EXC 306/2).Susanne Hartmann and Friederike Ebner were supported by the German Research Foundation (GRK 2046).Hans Minderman was supported by NIH R50CA211108.This work was funded by the Deutsche Forschungsgemeinschaft through the grant TRR130 (project P11 and C03) to Thomas H. Winkler.Ramon Bellmàs Sanz, Jenny Kühne, and Christine S. Falk thank Jana Keil and Kerstin Daemen for excellent technical support. The work was funded by the Germany Research Foundation CRC738/B3 (CSF).The work by the Mei laboratory was supported by German Research Foundation Grant ME 3644/5‐1 and TRR130 TP24, the German Rheumatism Research Centre Berlin, European Union Innovative Medicines Initiative ‐ Joint Undertaking ‐ RTCure Grant Agreement 777357, the Else Kröner‐Fresenius‐Foundation, German Federal Ministry of Education and Research e:Med sysINFLAME Program Grant 01ZX1306B and KMU‐innovativ 'InnoCyt', and the Leibniz Science Campus for Chronic Inflammation (http://www.chronische-entzuendung.org).Axel Ronald Schulz, Antonio Cosma, Sabine Baumgart, Brice Gaudilliere, Helen M. McGuire, and Henrik E. Mei thank Michael D. Leipold for critically reading the manuscript.Christian Kukat acknowledges support from the ISAC SRL Emerging Leaders program.John Trowsdale received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement 695551)., European Project: 7728036(1978), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Università degli Studi di Milano = University of Milan (UNIMI), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universität Heidelberg [Heidelberg] = Heidelberg University, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Oxford-NIHR Biomedical Research Centre, Universität Bonn = University of Bonn, Università degli Studi di Firenze = University of Florence (UniFI), Università degli studi di Genova = University of Genoa (UniGe), Universidad de Salamanca, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Université de Lausanne = University of Lausanne (UNIL), Universität Leipzig, Universiteit Gent = Ghent University (UGENT), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Cossarizza, A., Chang, H. -D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W., Aghaeepour, N., Akdis, M., Allez, M., Almeida, L. N., Alvisi, G., Anderson, G., Andra, I., Annunziato, F., Anselmo, A., Bacher, P., Baldari, C. T., Bari, S., Barnaba, V., Barros-Martins, J., Battistini, L., Bauer, W., Baumgart, S., Baumgarth, N., Baumjohann, D., Baying, B., Bebawy, M., Becher, B., Beisker, W., Benes, V., Beyaert, R., Blanco, A., Boardman, D. A., Bogdan, C., Borger, J. G., Borsellino, G., Boulais, P. E., Bradford, J. A., Brenner, D., Brinkman, R. R., Brooks, A. E. S., Busch, D. H., Buscher, M., Bushnell, T. P., Calzetti, F., Cameron, G., Cammarata, I., Cao, X., Cardell, S. L., Casola, S., Cassatella, M. A., Cavani, A., Celada, A., Chatenoud, L., Chattopadhyay, P. K., Chow, S., Christakou, E., Cicin-Sain, L., Clerici, M., Colombo, F. S., Cook, L., Cooke, A., Cooper, A. M., Corbett, A. J., Cosma, A., Cosmi, L., Coulie, P. G., Cumano, A., Cvetkovic, L., Dang, V. D., Dang-Heine, C., Davey, M. S., Davies, D., De Biasi, S., Del Zotto, G., Dela Cruz, G. V., Delacher, M., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Di Santo, J. P., Diefenbach, A., Dieli, F., Dolf, A., Dorner, T., Dress, R. J., Dudziak, D., Dustin, M., Dutertre, C. -A., Ebner, F., Eckle, S. B. G., Edinger, M., Eede, P., Ehrhardt, G. R. A., Eich, M., Engel, P., Engelhardt, B., Erdei, A., Esser, C., Everts, B., Evrard, M., Falk, C. S., Fehniger, T. A., Felipo-Benavent, M., Ferry, H., Feuerer, M., Filby, A., Filkor, K., Fillatreau, S., Follo, M., Forster, I., Foster, J., Foulds, G. A., Frehse, B., Frenette, P. S., Frischbutter, S., Fritzsche, W., Galbraith, D. W., Gangaev, A., Garbi, N., Gaudilliere, B., Gazzinelli, R. T., Geginat, J., Gerner, W., Gherardin, N. A., Ghoreschi, K., Gibellini, L., Ginhoux, F., Goda, K., Godfrey, D. I., Goettlinger, C., Gonzalez-Navajas, J. M., Goodyear, C. S., Gori, A., Grogan, J. L., Grummitt, D., Grutzkau, A., Haftmann, C., Hahn, J., Hammad, H., Hammerling, G., Hansmann, L., Hansson, G., Harpur, C. M., Hartmann, S., Hauser, A., Hauser, A. E., Haviland, D. L., Hedley, D., Hernandez, D. C., Herrera, G., Herrmann, M., Hess, C., Hofer, T., Hoffmann, P., Hogquist, K., Holland, T., Hollt, T., Holmdahl, R., Hombrink, P., Houston, J. P., Hoyer, B. F., Huang, B., Huang, F. -P., Huber, J. E., Huehn, J., Hundemer, M., Hunter, C. A., Hwang, W. Y. K., Iannone, A., Ingelfinger, F., Ivison, S. M., Jack, H. -M., Jani, P. K., Javega, B., Jonjic, S., Kaiser, T., Kalina, T., Kamradt, T., Kaufmann, S. H. E., Keller, B., Ketelaars, S. L. C., Khalilnezhad, A., Khan, S., Kisielow, J., Klenerman, P., Knopf, J., Koay, H. -F., Kobow, K., Kolls, J. K., Kong, W. T., Kopf, M., Korn, T., Kriegsmann, K., Kristyanto, H., Kroneis, T., Krueger, A., Kuhne, J., Kukat, C., Kunkel, D., Kunze-Schumacher, H., Kurosaki, T., Kurts, C., Kvistborg, P., Kwok, I., Landry, J., Lantz, O., Lanuti, P., Larosa, F., Lehuen, A., LeibundGut-Landmann, S., Leipold, M. D., Leung, L. Y. T., Levings, M. K., Lino, A. C., Liotta, F., Litwin, V., Liu, Y., Ljunggren, H. -G., Lohoff, M., Lombardi, G., Lopez, L., Lopez-Botet, M., Lovett-Racke, A. E., Lubberts, E., Luche, H., Ludewig, B., Lugli, E., Lunemann, S., Maecker, H. T., Maggi, L., Maguire, O., Mair, F., Mair, K. H., Mantovani, A., Manz, R. A., Marshall, A. J., Martinez-Romero, A., Martrus, G., Marventano, I., Maslinski, W., Matarese, G., Mattioli, A. V., Maueroder, C., Mazzoni, A., Mccluskey, J., Mcgrath, M., Mcguire, H. M., Mcinnes, I. B., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Miller, S. D., Mills, K. H. G., Minderman, H., Mjosberg, J., Moore, J., Moran, B., Moretta, L., Mosmann, T. R., Muller, S., Multhoff, G., Munoz, L. E., Munz, C., Nakayama, T., Nasi, M., Neumann, K., Ng, L. G., Niedobitek, A., Nourshargh, S., Nunez, G., O'Connor, J. -E., Ochel, A., Oja, A., Ordonez, D., Orfao, A., Orlowski-Oliver, E., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Pattanapanyasat, K., Paulsen, M., Pavlinic, D., Penter, L., Peterson, P., Peth, C., Petriz, J., Piancone, F., Pickl, W. F., Piconese, S., Pinti, M., Pockley, A. G., Podolska, M. J., Poon, Z., Pracht, K., Prinz, I., Pucillo, C. E. M., Quataert, S. A., Quatrini, L., Quinn, K. M., Radbruch, H., Radstake, T. R. D. J., Rahmig, S., Rahn, H. -P., Rajwa, B., Ravichandran, G., Raz, Y., Rebhahn, J. A., Recktenwald, D., Reimer, D., Reis e Sousa, C., Remmerswaal, E. B. M., Richter, L., Rico, L. G., Riddell, A., Rieger, A. M., Robinson, J. P., Romagnani, C., Rubartelli, A., Ruland, J., Saalmuller, A., Saeys, Y., Saito, T., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sandrock, I., Santoni, A., Sanz, R. B., Saresella, M., Sautes-Fridman, C., Sawitzki, B., Schadt, L., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schimisky, E., Schlitzer, A., Schlosser, J., Schmid, S., Schmitt, S., Schober, K., Schraivogel, D., Schuh, W., Schuler, T., Schulte, R., Schulz, A. R., Schulz, S. R., Scotta, C., Scott-Algara, D., Sester, D. P., Shankey, T. V., Silva-Santos, B., Simon, A. K., Sitnik, K. M., Sozzani, S., Speiser, D. E., Spidlen, J., Stahlberg, A., Stall, A. M., Stanley, N., Stark, R., Stehle, C., Steinmetz, T., Stockinger, H., Takahama, Y., Takeda, K., Tan, L., Tarnok, A., Tiegs, G., Toldi, G., Tornack, J., Traggiai, E., Trebak, M., Tree, T. I. M., Trotter, J., Trowsdale, J., Tsoumakidou, M., Ulrich, H., Urbanczyk, S., van de Veen, W., van den Broek, M., van der Pol, E., Van Gassen, S., Van Isterdael, G., van Lier, R. A. W., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H. -D., von Borstel, A., von Volkmann, K., Waisman, A., Walker, R. V., Wallace, P. K., Wang, S. A., Wang, X. M., Ward, M. D., Ward-Hartstonge, K. A., Warnatz, K., Warnes, G., Warth, S., Waskow, C., Watson, J. V., Watzl, C., Wegener, L., Weisenburger, T., Wiedemann, A., Wienands, J., Wilharm, A., Wilkinson, R. J., Willimsky, G., Wing, J. B., Winkelmann, R., Winkler, T. H., Wirz, O. F., Wong, A., Wurst, P., Yang, J. H. M., Yang, J., Yazdanbakhsh, M., Yu, L., Yue, A., Zhang, H., Zhao, Y., Ziegler, S. M., Zielinski, C., Zimmermann, J., Zychlinsky, A., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, Netherlands Organization for Scientific Research, German Research Foundation, European Commission, European Research Council, Repositório da Universidade de Lisboa, CCA - Imaging and biomarkers, Experimental Immunology, AII - Infectious diseases, AII - Inflammatory diseases, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, and Landsteiner Laboratory
Subjects: 0301 basic medicine, Consensus, Immunology, Consensu, Cell Separation, Biology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Guidelines, Allergy and Immunology, medicine, Cell separation, Immunology and Allergy, Humans, guidelines, flow cytometry, immunology, medicine.diagnostic_test, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Cell sorting, Flow Cytometry, Cell selection, Data science, 3. Good health, 030104 developmental biology, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, 030215 immunology, Human
Abstract: All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).
Published: 2019

48. Solving the enigma of POLD1 p.V295M as a potential cause of increased cancer risk

Author: Rebeca Sanz-Pamplona, Conxi Lázaro, Tirso Pons, Sandra García-Mulero, Laura Valle, Jesús del Valle, Elsa Ezquerro, Lorena Magraner-Pardo, Pilar Mur, Gabriel Capellá, Victor Moreno, and Anna Díez-Villanueva
Subjects: Adenoma, Genetics, Exonuclease, POLD1, biology, Cancer, DNA Polymerase II, Brief Communication, medicine.disease, Germline, Frameshift mutation, biology.protein, medicine, Humans, Missense mutation, Proofreading, Colorectal Neoplasms, Poly-ADP-Ribose Binding Proteins, Germ-Line Mutation, Genetics (clinical), Polymerase, DNA Polymerase III
Abstract: Germline variants that affect the proofreading activity of polymerases epsilon (POLE) and delta (POLD1) predispose to colorectal adenomas and carcinomas, among other cancers. All cancer-associated pathogenic variants reported to date consist of non-disruptive genetic changes affecting the sequence that codifies the exonuclease domain (ED). Generally, disruptive (frameshift, stop-gain) POLE and POLD1 variants and missense variants outside the ED do not predispose to cancer. However, this statement may not be true for some, very specific variants that would indirectly affect the proofreading activity of the corresponding polymerase. We evaluated, by using multiple approaches, the possibility that POLD1 c.883G>A; p.(Val295Met), -a variant located 9 amino acids upstream the ED and present in ~0.25% of hereditary cancer patients-, affects POLD1 proofreading activity. Our findings show cumulative evidence that support no alteration of the proofreading activity and lack of association with cancer. The variant is classified as likely benign according to the ACMG/AMP guidelines.
Published: 2021

49. Decreased Glucose Metabolism and Glutamine Synthesis in the Retina of a Transgenic Mouse Model of Alzheimer’s Disease

Author: Blanca I. Aldana, Emil W. Westi, Rupali Vohra, Jens Hannibal, Miriam Kolko, Zaynab Ahmad Mouhammad, Berta Sanz-Morello, Kristine K. Freude, Anna Luna Mølgaard Tams, and Jens V. Andersen
Subjects: Genetically modified mouse, medicine.medical_specialty, Cell type, Retina, genetic structures, Neurodegeneration, Retinal, Cell Biology, General Medicine, Biology, medicine.disease, Retinal ganglion, eye diseases, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Endocrinology, medicine.anatomical_structure, chemistry, Internal medicine, medicine, sense organs, Muller glia, Neuroinflammation
Abstract: Visual changes are some of the earliest symptoms that patients with Alzheimer’s disease (AD) experience. Pathophysiological processes such as amyloid-β plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells (RGCs) have been detected in the retina of AD patients and animal models. However, little is known about the molecular processes that underlie retinal neurodegeneration in AD. The cellular architecture and constant sensory activity of the retina impose high metabolic demands. We thus hypothesized that energy metabolism might be compromised in the AD retina similarly to what has been observed in the AD brain. To address this question, we explored cellular alterations and retinal metabolic activity in the 5 × FAD mouse model of AD. We used 8-month-old female 5 × FAD mice, in which the AD-related pathology has been shown to be apparent. We observed that RGC density is selectively affected in the retina of 5 × FAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U-13C] glucose and analyzed tissue extracts by gas chromatography-mass spectrometry. We found that the retinas of 5 × FAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5 × FAD retinas but no changes in the expression of markers of Muller glia, the main glial cell type responsible for glutamate uptake and glutamine synthesis in the retina. These findings suggest that AD presents with metabolic alterations not only in the brain but also in the retina that may be detrimental to RGC activity and survival, potentially leading to the visual impairments that AD patients suffer.
Published: 2021

50. Carpobrotus Management in a Mediterranean Sand Dune Ecosystem: Minimum Effective Glyphosate Dose and an Evaluation of Tarping

Author: Borja Sanz, Mariano Fos, and Enrique Sanchis
Subjects: Mediterranean climate, biology, Carpobrotus, biology.organism_classification, Invasive species, Sand dune stabilization, chemistry.chemical_compound, Agronomy, chemistry, Glyphosate, Environmental science, Ecosystem, Chemical control, Ecology, Evolution, Behavior and Systematics, General Environmental Science
Published: 2021

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