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1. Defects in AMPAR trafficking and microglia activation underlie socio-cognitive deficits associated to decreased expression of phosphodiesterase 2 a

Author

Sébastien Delhaye, Marielle Jarjat, Asma Boulksibat, Clara Sanchez, Alessandra Tempio, Andrei Turtoi, Mauro Giorgi, Sandra Lacas-Gervais, Gabriele Baj, Carole Rovere, Viviana Trezza, Manuela Pellegrini, Thomas Maurin, Enzo Lalli, and Barbara Bardoni

Subjects
cAMP and cGMP pathways, PDE2A, Autism Spectrum disorder, Intellectual disability, Mouse model, mGluR-dependent LTD, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Phosphodiesterase 2 A (PDE2A) is an enzyme involved in the homeostasis of cAMP and cGMP and is the most highly expressed PDE in human brain regions critical for socio-cognitive behavior. In cerebral cortex and hippocampus, PDE2A expression level is upregulated in Fmr1-KO mice, a model of the Fragile X Syndrome (FXS), the most common form of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Indeed, PDE2A translation is negatively modulated by FMRP, whose functional absence causes FXS. While the pharmacological inhibition of PDE2A has been associated to its pro-cognitive role in normal animals and in models of ID and ASD, homozygous PDE2A mutations have been identified in patients affected by ID, ASD and epilepsy. To clarify this apparent paradox about the role of PDE2A in brain development, we characterized here Pde2a+/− mice (homozygote animals being not viable) at the behavioral, cellular, molecular and electrophysiological levels. Pde2a+/− females display a milder form of the disorder with reduced cognitive performance in adulthood, conversely males show severe socio-cognitive deficits throughout their life. In males, these phenotypes are associated with microglia activation, elevated glutathione levels and increased externalization of Glutamate receptor (GluR1) in CA1, producing reduced mGluR-dependent Long-term Depression. Overall, our results reveal molecular targets of the PDE2A-dependent pathway underlying socio-cognitive performance. These results clarify the mechanism of action of pro-cognitive drugs based on PDE2A inactivation, which have been shown to be promising therapeutic approaches for Alzheimer's disease, schizophrenia, FXS as well as other forms of ASD.

Published
2024
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2. Soil-borne fungi alter the apoplastic purinergic signaling in plants by deregulating the homeostasis of extracellular ATP and its metabolite adenosine

Author

Christopher Kesten, Valentin Leitner, Susanne Dora, James W Sims, Julian Dindas, Cyril Zipfel, Consuelo M De Moraes, and Clara Sanchez-Rodriguez

Subjects
Fusarium oxysporum, Adenosine, apoplast, Medicine, Science, Biology (General), QH301-705.5
Abstract

Purinergic signaling activated by extracellular nucleotides and their derivative nucleosides trigger sophisticated signaling networks. The outcome of these pathways determine the capacity of the organism to survive under challenging conditions. Both extracellular ATP (eATP) and Adenosine (eAdo) act as primary messengers in mammals, essential for immunosuppressive responses. Despite the clear role of eATP as a plant damage-associated molecular pattern, the function of its nucleoside, eAdo, and of the eAdo/eATP balance in plant stress response remain to be fully elucidated. This is particularly relevant in the context of plant-microbe interaction, where the intruder manipulates the extracellular matrix. Here, we identify Ado as a main molecule secreted by the vascular fungus Fusarium oxysporum. We show that eAdo modulates the plant’s susceptibility to fungal colonization by altering the eATP-mediated apoplastic pH homeostasis, an essential physiological player during the infection of this pathogen. Our work indicates that plant pathogens actively imbalance the apoplastic eAdo/eATP levels as a virulence mechanism.

Published
2023
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4. The companion of cellulose synthase 1 confers salt tolerance through a Tau-like mechanism in plants

Author

Christopher Kesten, Arndt Wallmann, René Schneider, Heather E. McFarlane, Anne Diehl, Ghazanfar Abbas Khan, Barth-Jan van Rossum, Edwin R. Lampugnani, Witold G. Szymanski, Nils Cremer, Peter Schmieder, Kristina L. Ford, Florian Seiter, Joshua L. Heazlewood, Clara Sanchez-Rodriguez, Hartmut Oschkinat, and Staffan Persson

Subjects
Science
Abstract

The Arabidopsis CC1 protein maintains microtubule array stability and cellulose synthesis during salt stress. Here the authors show that CC1 engages microtubules via an intrinsically disordered N-terminus that suggests it controls microtubule dynamics in a similar way to the mammalian Tau protein.

Published
2019
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5. Estabilidad y nivel óseo periimplantario de implantes postextractivos en pacientes de la tercera edad

Author

Orlando Guerra Cobian, Clara Sanchez Silot, and Jorge Luis García Romero

Subjects
implantes postextractivos, estabilidad, pérdida ósea periimplantaria, adulto mayor., Medicine (General), R5-920, Public aspects of medicine, RA1-1270
Abstract

Introducción: Los implantes postextractivos acortan el tiempo en lograr la rehabilitación del paciente, resulta esta condicionante un factor esencial para devolver la calidad de vida en corto plazo a un adulto mayor y mejorar rápidamente su función masticatoria. Objetivo: Determinar los valores de estabilidad y la pérdida ósea periimplantaria en implantes postextractivos en pacientes de la tercera edad. Material y Método: Se realizó un estudio cuasi-experimental en 99 pacientes de la tercera edad en la Facultad de Estomatología ¨Raúl González Sánchez¨, 2017-2019. Bajo su consentimiento se colocaron 173 implantes postextractivos. Se determinó tipo de hueso de soporte, estabilidad primaria y secundaria según análisis de frecuencia de resonancia con Osstel Mentor. Se midió el nivel óseo periimplantario y la pérdida ósea hasta 12 meses de colocada la rehabilitación. Resultados: Se posicionaron mayoritariamente implantes en el sitio de implantación incisivo maxilar en 43,3 % de los casos. Los valores promedio de estabilidad primaria y secundaria fueron 48 ISQ y 68 ISQ respectivamente. La pérdida ósea promedio tras un año de rehabilitación fue de 1,04±0,22mm. Conclusiones: Los implantes dentales postextractivos en pacientes de la tercera edad se insertaron preferentemente en el grupo incisivo maxilar y en hueso tipo D2, registraron una estabilidad primaria promedio moderada y una estabilidad secundaria promedio substancial. La pérdida ósea vertical periimplantaria exhibió valores semejantes a los implantes en zonas curadas y dentro del valor estandarizado para pérdida ósea periimplantaria para el primer año tras su colocación.

Published
2020

6. The Neuropeptide Cortistatin Alleviates Neuropathic Pain in Experimental Models of Peripheral Nerve Injury

Author

Clara P. Falo, Raquel Benitez, Marta Caro, Maria Morell, Irene Forte-Lago, Pedro Hernandez-Cortes, Clara Sanchez-Gonzalez, Francisco O’Valle, Mario Delgado, and Elena Gonzalez-Rey

Subjects
neuropathic pain, neuropeptide, neuroprotection, neuroregeneration, peripheral nerve injury, neuroinflammation, Pharmacy and materia medica, RS1-441
Abstract

Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.

Published
2021
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7. Unmarried Mothers on the English Stage after the Godly Revolution/Madres solteras en la escena inglesa tras la Revolucion gloriosa

Author

Trigo, Clara Sanchez

Subjects
The Marriage-Hater Matched (Play) -- Criticism and interpretation, The Squire of Alsatia (Play) -- Criticism and interpretation, Dramatists -- Criticism and interpretation, Unmarried mothers -- Portrayals, Languages and linguistics, Literature/writing, Criticism and interpretation, Portrayals
Abstract

Unmarried mothers and children born out of wedlock are notoriously absent from the Carolean stage, which, on the other hand, saw an abundance of rakish gallants and prostitutes populating sexually charged plots. It is not a coincidence that the only two plays premiered between 1660 and 1700 featuring an unmarried woman with a living child arrive just around the time that William and Mary take the throne. This paper analyses the ways in which these two plays--The Squire of Alsatia (1688) by Thomas Shadwell and The Marriage-Hater Matched (1692) by Thomas Durfey--use the unmarried mother to convey a moral message that echoed William and Mary's project of moral reform. However, these women are portrayed in radically different ways in the two comedies. Although she is customarily portrayed as a despicable character in The Squire of Alsatia, the unmarried mother in The Marriage-Hater Matched gets to be a good-hearted heroine who is eventually redeemed. This was a very challenging position for Durfey to portray, requiring of intra- and extra textual devices to support her redemption without appearing to condone vice. Keywords: Restoration comedy; mothers; moral reform; Thomas Durfey; Thomas Shadwell Las madres solteras y los ninos nacidos fuera del matrimonio estan significativamente ausentes de la escena carolina, en la cual, por otra parte, existia un abundante numero de galantes libertinos y prostitutas que formaban parte de argumentos cargados de sexualidad. No es casualidad que las dos unicas obras estrenadas entre 1660 y 1700 con una madre soltera entre sus personajes se vean justo en la epoca en que Guillermo y Maria suben al trono. Este articulo analiza las formas en que estas dos obras--The Squire of Alsatia (1688), de Thomas Shadwell y The Marriage-Hater Matched (1692), de Thomas Durfey--utilizan a la madre soltera para transmitir un mensaje moral que se hace eco del proyecto de reforma de indole moral de Guillermo y Maria. Sin embargo, estas mujeres son descritas de maneras radicalmente diferentes en las dos comedias. Mientras que en The Squire of Alsatia se representa a la madre soltera como un personaje despreciable, en The Marriage-Hater Matched esta se convierte en una heroina de buen corazon que finalmente es redimida, una posicion muy dificil de retratar para Durfey, que requirio de recursos intratextuales y extratextuales para transmitir la idea de redencion sin que pareciera que se admitia el vicio. Palabras clave: Comedia de la Restauracion; madres; reforma moral; Thomas Durfey; Thomas Shadwell, Carolean comedy revelled in complex plots where prostitutes, hypocritical Puritans, rascals and bullies rubbed shoulders with ladies and gentlemen of quality. Debauchery and licentiousness were necessary attitudes for comic gentlemen [...]

Published
2024
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8. Neurodevelopmental and growth outcomes after invasive Group B Streptococcus in early infancy: A multi-country matched cohort study in South Africa, Mozambique, India, Kenya, and Argentina

Author

Madhi, Shabir A., Dangor, Ziyaad, Leahy, Shannon, Harden, Lois, Ghoor, Azra, Mbatha, Sibongile, Lowick, Sarah, Laughton, Barbara, Jaye, Tamara, Lala, Sanjay G, Sithole, Pamela, Msayi, Jacqueline, Kumalo, Ntombifuthi, Msibi, Tshepiso Nompumelelo, Santhanam, Sridhar, John, Hima B., Arumugam, Asha, Murugesan, Nandhini, Rajendraprasad, Nandhini, Priya, Mohana, Abubakar, Amina, Nasambu, Carophine, Adan, Adam Mabrouk, Katana, Patrick Vidzo, Mwangome, Eva, Newton, Charles R., Bassat, Quique, Bardají, Azucena, Bramugy, Justina, Mucasse, Humberto, Aerts, Celine, Massora, Sergio, Libster, Romina, Yanotti, Clara Sánchez, Medina, Valeria, Rojas, Andrea, Amado, Daniel, Llapur, Conrado J., Hossain, A.K.M. Tanvir, Sadeq-ur Rahman, Qazi, Paul, Proma, Chandna, Jaya, Procter, Simon R., Seedat, Farah, Horváth-Puhó, Erzsébet, Jit, Mark, Milner, Kate, Gonçalves, Bronner P., and Lawn, Joy E.

Published
2022
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10. DIAGNÓSTICO DAS LEIS ESTADUAIS DE INCENTIVO AO ESPORTE NO BRASIL

Author

Sabrina de Lima Vitório, Leandro Eduardo Cerbi, Bruna Lindman Bueno, Clara Sanchez da Trindade Santos, and Leandro Carlos Mazzei

Subjects
General Medicine
Abstract

Com a criação da Lei Federal de Incentivo ao Esporte em 2006 e na onda dos Megaeventos Esportivos no Brasil, muitos Estados criaram suas próprias iniciativas relacionadas à isenção fiscal para favorecimento do Esporte. No entanto, a bibliografia sobre este fenômeno é escassa. Assim, este estudo teve por objetivo apresentar um diagnóstico das Leis de Incentivo ao Esporte (LIEs) no âmbito Estadual, indicando as características destas ações realizadas pelas unidades federativas. Trata-se de um estudo de caráter descritivo, utilizando de fontes documentais para a coleta de dados obtidas através dos sites oficiais de cada Secretaria ou órgão semelhante responsável pelas Políticas Públicas do Esporte nos Estados. Foram identificadas ações relacionadas ao incentivo do esporte via isenção fiscal em 15 Estados e todas envolvem o tributo ICMS. Verificou-se ainda uma variação grande com relação às porcentagens de valor destinadas, bem como uma diversificação das manifestações esportivas em cada Estado.

Published
2021
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11. Predictors of cardiovascular events and all‐cause of death in patients with transfusion‐dependent myelodysplastic syndrome

Author

Tamara Jimenez-Solas, Agustín C. Martín-García, Teresa Gonzalez-Martinez, Elena Díaz-Peláez, Marta Alonso-Fernández-Gatta, Ana Martín-García, Félix López-Cadenas, Pedro L. Sánchez, María Díez-Campelo, Clara Sanchez-Pablo, Junta de Castilla y León, and Instituto de Salud Carlos III

Subjects
Male, Risk, medicine.medical_specialty, Iron Overload, Multivariate analysis, Heart disease, Population, Kaplan-Meier Estimate, Disease, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, Internal medicine, Humans, Medicine, Blood Transfusion, Prospective Studies, education, Prospective cohort study, Pathological, Aged, Cause of death, Aged, 80 and over, education.field_of_study, business.industry, Hematology, Middle Aged, T1 mapping, Prognosis, Cardiovascular disease, medicine.disease, Magnetic Resonance Imaging, Log-rank test, Feature tracking, Cardiovascular Diseases, NT-proBNP, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Cardiology, Female, business, Myelodysplastic syndrome, Biomarkers, Follow-Up Studies, 030215 immunology
Abstract

Cardiovascular disease (CVD) involves the second cause of death in low-risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all-cause mortality in transfusion dependent low-risk MDS patients. Thirty-one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow-up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT-proBNP ≥ 486pg/ml (HR 96·7; 95%-CI 1·135–8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%-CI 1·235–1623; P = 0·038) and higher left ventricular global longitudinal strain (LV-GLS) (HR 0·4; 95%-CI 0·196–0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low-risk MDS patients frequently suffer CVD. NT-proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high-risk patients who could benefit from a cardiac treatment and follow-up., This work was funded by aGerencia Regional de Salud de Castilla y León grant(GRS1203/A/15) and a Rıo Hortega contract (CM19/00055),supported by the Instituto de Salud Carlos III in Spain (co-funded by the European Social Fund ‘Investing in yourfuture’).

Published
2021
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12. Scalable Production of Ambient Stable Hybrid Bismuth‐Based Materials: AACVD of Phenethylammonium Bismuth Iodide Films**

Author

Clara Sanchez-Perez, M. Wang, M. O. Blunt, Claire J. Carmalt, and F. Habib

Subjects
Full Paper, 010405 organic chemistry, Band gap, Chemistry, Organic Chemistry, chemistry.chemical_element, Heterojunction, General Chemistry, Chemical vapor deposition, Full Papers, light-harvesting, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Bismuth, Characterization (materials science), lead-free hybrid material, Band bending, Chemical engineering, phenethylammonium bismuth iodide, Hybrid material, scalability, Deposition (law)
Abstract

Large homogeneous and adherent coatings of phenethylammonium bismuth iodide were produced using the cost‐effective and scalable aerosol‐assisted chemical vapor deposition (AACVD) methodology. The film morphology was found to depend on the deposition conditions and substrates, resulting in different optical properties to those reported from their spin‐coated counterparts. Optoelectronic characterization revealed band bending effects occurring between the hybrid material and semiconducting substrates (TiO2 and FTO) due to heterojunction formation, and the optical bandgap of the hybrid material was calculated from UV‐visible and PL spectrometry to be 2.05 eV. Maximum values for hydrophobicity and crystallographic preferential orientation were observed for films deposited on FTO/glass substrates, closely followed by values from films deposited on TiO2/glass substrates., Compact and stable bismuth halide‐based hybrid material thin films were grown using aerosol‐assisted chemical vapor deposition. The dependence of structural and optoelectronic properties of phenethylammonium bismuth iodide films were evaluated on varying substrates, deposition temperatures and curing conditions. The morphology and optical band‐bending effects were related to synthetic parameters, and crack‐free films were obtained with high moisture resistance.

Published
2021
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13. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Author

Eduardo Bergel, Alejandra Debonis, Ignacio Esteban, Sofia Jares Baglivo, Sofia Sol Aranda, Ramiro Manuel Larrea, Jorge Lantos, Nicolás Kreplak, Candela Etchegaray, Yvonne Ritou, Mabel Berrueta, Ricardo Valentini, Fernando Althabe, Pablo Cruz, Gabriel Leberzstein, Alvaro Ciganda, Sofia Lujan Laudanno, Damian Alvarez Paggi, Fernando Alvez, Susana Pastor Arguello, Luz Gibbons, Alejandra Hintze, M Laura Oyarvide, Clara Sanchez Yanotti, Miguel Santiago Gonzalez, Romina Libster, Gaston Ofman, Federico Cesar Etchenique, Rocio Lopez Castelo, Cristian Wood, Fernando P. Polack, Maria Dolores Silveyra, Alejandra Neira, Ivonne Name, Sebastian Esperante, Gisela Caruso, Nicolas Itcovici, Julian De Luca, Silvina Coviello, Anibal Rondan, Rocio Rodriguez, Valeria Fernandez Vina, Gabriela Lescano, Gonzalo Pérez Marc, Federico Dimase, Dario Raul Alvarez, Virginia Braem, Alejandra Bianchi, Julieta Alfonso, Sofia Rapelius, Adrián Ferreti, Eduardo Perez, Mauricio T. Caballero, Juan Molinos, Diego Wappner, and Florencia Nowogrodzki

Subjects
Relative risk reduction, medicine.medical_specialty, Respiratory rate, Population, 030204 cardiovascular system & hematology, Placebo, law.invention, Plasma, purl.org/becyt/ford/3.3 [https], 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Severity of illness, medicine, Humans, 030212 general & internal medicine, education, COVID-19 Serotherapy, education.field_of_study, SARS-CoV-2, Transfusion Medicine, business.industry, Respiratory disease, Immunization, Passive, COVID-19, General Medicine, medicine.disease, Hospitals, Older adults, Relative risk, purl.org/becyt/ford/3 [https], Original Article, business
Abstract

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.). Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Pérez Marc, Gonzalo. Hospital Militar Central, Buenos Aires; Argentina Fil: Wappner, Diego. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Bianchi, Alejandra. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Braem, Virginia. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wood, Cristian. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Berrueta, Mabel. Hospital Militar Central; Argentina Fil: Rondan, Aníbal. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Lescano, Gabriela Mariel. Hospital Dr. Carlos Bocalandro; Argentina Fil: Cruz, Pablo. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Ritou, Yvonne. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Fernández Viña, Valeria Silvina. Hospital Simplemente Evita; Argentina Fil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Ferreti, Adrián. Hospital Dr. Carlos Bocalandro; Argentina Fil: Ofman, Gaston. University of Oklahoma; Estados Unidos Fil: Ciganda, Álvaro. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; Argentina Fil: Rodriguez, Rocío. Hospital Simplemente Evita; Argentina Fil: Lantos, Jorge. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Valentini, Ricardo. No especifíca; Fil: Itcovici, Nicolás. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Hintze, Alejandra. No especifíca; Fil: Oyarvide, M. Laura. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Etchegaray, Candela. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Neira, Alejandra. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Name, Ivonne. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Alfonso, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Swiss Medical Group; Argentina Fil: López Castelo, Rocío. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina Fil: Caruso, Gisela. Hospital Militar Central; Argentina Fil: Rapelius, Sofía. Hospital Militar Central; Argentina Fil: Alvez, Fernando. Hospital Militar Central; Argentina Fil: Etchenique, Federico. Hospital Militar Central; Argentina Fil: Dimase, Federico. Hospital Militar Central; Argentina Fil: Alvarez, Darío. Hospital Militar Central; Argentina Fil: Aranda, Sofía S.. Hospital Militar Central; Argentina Fil: Sánchez Yanotti, Clara Inés. Hospital Militar Central; Argentina Fil: De Luca, Julián. Hospital Militar Central; Argentina Fil: Jares Baglivo, Sofía. Hospital Militar Central; Argentina Fil: Laudanno, Sofía. Fundación Hematológica Sarmiento; Argentina Fil: Nowogrodzki, Florencia. Swiss Medical Group; Argentina Fil: Larrea, Ramiro. Hospital Municipal San Isidro; Argentina Fil: Silveyra, María. Hospital Militar Central; Argentina Fil: Leberzstein, Gabriel. No especifíca; Fil: Debonis, Alejandra. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Molinos, Juan. Fundación para la Investigación en Infectología Infantil; Argentina Fil: González, Miguel. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Perez, Eduardo. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Kreplak, Nicolás. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Pastor Argüello, Susana. Fundación para la Investigación en Infectología Infantil; Argentina Fil: Gibbons, Luz. Hospital Municipal de San Isidro; Argentina Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Bergel, Eduardo. Sanatorio Sagrado Corazón; Argentina Fil: Polack, Fernando Pedro. Provincia de Buenos Aires. Ministerio de Salud; Argentina

Published
2021
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14. DIAGNOSIS OF STATE SPORTS INCENTIVE LAWS IN BRAZIL

Author

Vitório, Sabrina de Lima, Cerbi, Leandro Eduardo, Lindman Bueno, Bruna, Santos, Clara Sanchez da Trindade, and Mazzei, Leandro Carlos

Subjects
Políticas Públicas, Leis Estaduais de Incentivo ao Esporte, Esporte, Política Pública, Public Policy, Deporte, Tax Exemption Laws, Leyes de Exención de Impuestos, Sport
Abstract

With the creation of the Federal Sports Incentive Law in 2006 and the Sporting Mega-Events held in Brazil, many states have created their own initiatives related to tax exemption to favor Sports. However, the bibliography on this phenomenon is scarce. Therefore, this study aimed to present a diagnosis of the Sports Incentive Laws at the State level, indicating the actions carried out by the federative units and their main characteristics. This is a descriptive study, using documental sources for data collection obtained through the official websites of each Secretariat or similar body responsible for the Sports Public Policies in the Brazilian States. Were identified 15 States actions related to the incentive to sports via tax exemption and all of them from the ‘ICMS’ tribute. It was also verified a large variation regarding the percentages of value allocated, as well as a great diversification of the sports manifestations in each State., Con la creación de la Ley Federal de Incentivo al Deporte y con los Mega-Eventos Deportivos en Brasil, muchos Estados Brasileños crearon sus iniciativas para favorecer el deporte a través de exenciones fiscales. Sin embargo, la bibliografía sobre este fenómeno es escasa. Por lo tanto, este estudio tuvo como objetivo presentar un diagnóstico de las Leyes de Incentivo al Deporte a nivel de los Estados Brasileños, indicando sus principales características. Se trata de un estudio descriptivo, que utiliza fuentes documentales obtenidos a través de los sitios web oficiales de cada Secretaría u organismo similar responsable de las Políticas Públicas de Deporte en los Estados. Se identificaron acciones relacionadas con el incentivo desportivo en 15 Estados y todos ellos relacionados com el impuestos ICMS. También se verificó una gran variación en cuanto a los porcentajes de valor destinados, así como una diversificación de las manifestaciones deportivas en cada Estado., Com a criação da Lei Federal de Incentivo ao Esporte em 2006 e na onda dos Megaeventos Esportivos no Brasil, muitos Estados criaram suas próprias iniciativas relacionadas à isenção fiscal para favorecimento do Esporte. No entanto, a bibliografia sobre este fenômeno é escassa. Assim, este estudo teve por objetivo apresentar um diagnóstico das Leis de Incentivo ao Esporte (LIEs) no âmbito Estadual, indicando as características destas ações realizadas pelas unidades federativas. Trata-se de um estudo de caráter descritivo, utilizando de fontes documentais para a coleta de dados obtidas através dos sites oficiais de cada Secretaria ou órgão semelhante responsável pelas Políticas Públicas do Esporte nos Estados. Foram identificadas ações relacionadas ao incentivo do esporte via isenção fiscal em 15 Estados e todas envolvem o tributo ICMS. Verificou-se ainda uma variação grande com relação às porcentagens de valor destinadas, bem como uma diversificação das manifestações esportivas em cada Estado.

Published
2021
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16. Aerosol-assisted route to low-E transparent conductive gallium-doped zinc oxide coatings from pre-organized and halogen-free precursor

Author

Jawwad A. Darr, Clara Sanchez-Perez, Claire J. Carmalt, Ivan P. Parkin, and Sebastian C. Dixon

Subjects
Materials science, business.industry, Band gap, Doping, chemistry.chemical_element, General Chemistry, Zinc, Chemical vapor deposition, Epitaxy, Chemistry, Glazing, chemistry, Optoelectronics, Charge carrier, Gallium, business
Abstract

Thermal control in low-emission windows is achieved by the application of glazings, which are simultaneously optically transparent in the visible and reflective in the near-infrared (IR). This phenomenon is characteristic of coatings with wide optical band gaps that have high enough charge carrier concentrations for the material to interact with electromagnetic radiation in the IR region. While conventional low-E coatings are composed of sandwiched structures of oxides and thin Ag films or of fluorinated SnO2 coatings, ZnO-based glazing offers an environmentally stable and economical alternative with competitive optoelectronic properties. In this work, gallium-doped zinc oxide (GZO) coatings with properties for low-E coatings that exceed industrial standards (Tvisible > 82%; R2500 nm > 90%; λ(plasma) = 1290 nm; ρ = 4.7 × 10−4 Ω cm; Rsh = 9.4 Ω·□−1) are deposited through a sustainable and environmentally friendly halogen-free deposition route from [Ga(acac)3] and a pre-organized zinc oxide precursor [EtZnOiPr]4 (1) via single-pot aerosol-assisted chemical vapor deposition. GZO films are highly (002)-textured, smooth and compact without need of epitaxial growth. The method herein describes the synthesis of coatings with opto-electronic properties commonly achievable only through high-vacuum methods, and provides an alternative to the use of pyrophoric ZnEt2 and halogenated SnO2 coatings currently used in low-emission glazing and photovoltaic technology., A pre-organised and halogen-free ZnO precursor is used to deposit GZO coatings via aerosol-assisted CVD with properties that exceed industrial standards for low-E coatings and photovoltaics.

Published
2020
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17. Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth

Author

Karina Mariño, Fátima Ferragut, María T. Elola, Silvia Vanzulli, Lucas L. Colombo, Clara Sanchez Terrero, Gabriel A. Rabinovich, María F. Troncoso, Carlota Wolfenstein-Todel, and Alejandro J. Cagnoni

Subjects
Fetal Proteins, 0301 basic medicine, CIENCIAS MÉDICAS Y DE LA SALUD, Cell Adhesion Molecules, Neuronal, Galectins, Triple Negative Breast Neoplasms, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, Cell Line, Tumor, Cell Adhesion, TRIPLE NEGATIVE BREAST CANCER, Animals, Humans, Cell adhesion, Receptor, Molecular Biology, ALCAM, Galectin, ALCAM (CD166), Chemistry, GALECTIN-8, SIALYLATION, Otras Medicina Básica, Activated-Leukocyte Cell Adhesion Molecule, CELL ADHESION AND MIGRATION, purl.org/becyt/ford/3.1 [https], Cell Biology, Adhesion, N-GLYCOSYLATION, Neoplasm Proteins, Cell biology, Medicina Básica, Galectin-8, 030104 developmental biology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Immunoglobulin superfamily, purl.org/becyt/ford/3 [https], Female, TUMOR GROWTH
Abstract

Galectin-8 (Gal-8), a ‘tandem-repeat’-type galectin, has been described as a modulator of cellular functions including adhesion, spreading, growth arrest, apoptosis, pathogen recognition, autophagy, and immunomodulation. We have previously shown that activated leukocyte cell adhesion molecule (ALCAM), also known as CD166, serves as a receptor for endogenous Gal-8. ALCAM is a member of the immunoglobulin superfamily involved in cell-cell adhesion through homophilic (ALCAM-ALCAM) and heterophilic (i.e. ALCAM-CD6) interactions in different tissues. Here we investigated the physiologic relevance of ALCAM-Gal-8 association and glycosylation-dependent mechanisms governing these interactions. We found that silencing of ALCAM in MDA-MB-231 triple negative breast cancer cells decreases cell adhesion and migration onto Gal-8-coated surfaces in a glycan-dependent fashion. Remarkably, either Gal-8 or ALCAM silencing also disrupted cell-cell adhesion, and led to reduced tumor growth in a murine model of triple negative breast cancer. Moreover, structural characterization of endogenous ALCAM N-glycosylation showed abundant permissive structures for Gal-8 binding. Importantly, we also found that cell sialylation controls Gal-8-mediated cell adhesion. Altogether, these findings demonstrate a central role of either ALCAM or Gal-8 (or both) in controlling triple negative breast cancer. Fil: Ferragut, Fatima Eneida del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Sánchez Terrero, Clara. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Wolfenstein Todel, Carlota. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Troncoso, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Mariño, Karina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Elola, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina

Published
2019
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18. The Neuropeptide Cortistatin Alleviates Neuropathic Pain in Experimental Models of Peripheral Nerve Injury

Author

Raquel Benitez, Pedro Hernández-Cortés, Mario Delgado, Marta Caro, Elena Gonzalez-Rey, CP Falo, Francisco O'Valle, Clara Sanchez-Gonzalez, Maria Morell, and Irene Forte-Lago

Subjects
Pharmaceutical Science, Pharmacology, Article, neuroinflammation, 03 medical and health sciences, 0302 clinical medicine, Pharmacy and materia medica, medicine, peripheral nerve injury, neuropeptide, neuroregeneration, 030304 developmental biology, neuropathic pain, 0303 health sciences, business.industry, Chronic pain, Nerve injury, medicine.disease, Cortistatin, RS1-441, Allodynia, Nociception, Peripheral nerve injury, Hyperalgesia, Neuropathic pain, neuroprotection, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.

Published
2021

19. Increasing detections of the margay: occupancy, density, and activity patterns in Madre de Dios, Peru

Author

Samantha Zwicker, Clara Sánchez-Latorre, and Clemens Lukasser

Subjects
behavioral ecology, home ranges, Leopardus wiedii, occupancy modeling, semiarboreal camera, spatial capture-recapture, Evolution, QH359-425, Ecology, QH540-549.5
Abstract

This study provides novel insights into the ecology of the margay (Leopardus wiedii), focusing on its occupancy, density, and activity patterns in the Madre de Dios region, Peru, by utilizing both arboreal and terrestrial camera traps. Conducted across 10 km2, the research achieved 47 detections, utilizing semi-arboreal, lower canopy cameras for the first time to capture margay activities. Occupancy models revealed a mean occupancy probability of 53.82% and a detection probability of 6.57%. Among the environmental covariates, diameter at breast height (DBH) was identified as a significant predictor, negatively impacting occupancy, suggesting margays favor areas with smaller tree diameters. Contrary to expectations, the Normalized Difference Vegetation Index (NDVI) did not significantly influence occupancy. Tree density exhibited a positive, though non-significant, association with margay presence. Spatial capture-recapture (SECR) models estimated a margay density of 71.46 individuals per 100 km², with significant sex-based differences in spatial behavior. Males demonstrated larger home ranges (approximately 13.50 km²) compared to females (approximately 3.79 km²). Activity pattern analyses indicated primary nocturnal behavior with peaks at midnight to 3 am, 5 am, and 6 pm. Temporal overlap analysis revealed a low overlap coefficient with jaguarundis (Dhat1 = 0.21) and a higher overlap with ocelots (Dhat4 = 0.79), reflecting intricate interspecies dynamics. Our findings highlight important ecological aspects of margay behavior, including habitat preferences, nocturnal activity patterns, and interspecies interactions, which were effectively captured through the combined use of terrestrial and arboreal camera traps. The study emphasizes the importance of habitat preservation and the development of conservation strategies tailored to the ecological needs of margays, potentially influencing global practices for the management and protection of lesser-studied semi-arboreal wild cats.

Published
2024
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20. Sustained antiviral response against in vitro HIV-1 infection in peripheral blood mononuclear cells from people with chronic myeloid leukemia treated with ponatinib

Author

Mario Manzanares, Fernando Ramos-Martín, Sara Rodríguez-Mora, Guiomar Casado-Fernández, Clara Sánchez-Menéndez, Alicia Simón-Rueda, Elena Mateos, Miguel Cervero, Adam M. Spivak, Vicente Planelles, Montserrat Torres, Valentín García-Gutiérrez, and Mayte Coiras

Subjects
HIV-1, ponatinib, cytotoxic immunity, antiviral response, chronic myeloid leukemia, Therapeutics. Pharmacology, RM1-950
Abstract

HIV-1 infection cannot be cured due to long-lived viral reservoirs formed by latently infected CD4+ T cells. “Shock and Kill” strategy has been considered to eliminate the viral reservoir and achieve a functional cure but the stimulation of cytotoxic immunity is necessary. Ponatinib is a tyrosine kinase inhibitor (TKI) clinically used against chronic myeloid leukemia (CML) that has demonstrated to be effective against HIV-1 infection in vitro. Several TKIs may induce a potent cytotoxic response against cancer cells that makes possible to discontinue treatment in people with CML who present long-term deep molecular response. In this longitudinal study, we analyzed the capacity of ponatinib to induce an antiviral response against HIV-1 infection in peripheral blood mononuclear cells (PBMCs) obtained from people with CML previously treated with imatinib for a median of 10 years who changed to ponatinib for 12 months to boost the anticancer response before discontinuing any TKI as part of the clinical trial NCT04043676. Participants were followed-up for an additional 12 months in the absence of treatment. PBMCs were obtained at different time points and then infected in vitro with HIV-1. The rate of infection was determined by quantifying the intracellular levels of p24-gag in CD4+ T cells. The levels of p24-gag+ CD4+ T−cells were lower when these cells were obtained during and after treatment with ponatinib in comparison with those obtained during treatment with imatinib. Cytotoxicity of PBMCs against HIV-infected target cells was significantly higher during treatment with ponatinib than during treatment with imatinib, and it was maintained at least 12 months after discontinuation. There was a significant negative correlation between the lower levels of p24-gag+ CD4+ T−cells and the higher cytotoxicity induced by PBMCs when cells were obtained during and after treatment with ponatinib. This cytotoxic immunity was mostly based on higher levels of Natural Killer and Tγδ cells seemingly boosted by ponatinib. In conclusion, transient treatment with immunomodulators like ponatinib along with ART could be explored to boost the antiviral activity of cytotoxic cells and contribute to the elimination of HIV-1 reservoir.

Published
2024
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21. Advances in the development of high efficiency III-V multijunction solar cells on Ge|Si virtual substrates

Author

Pere Roca i Cabarrocas, Victor Orejuela, Manuel Hinojosa, Monalisa Ghosh, Iván García, Clara Sanchez, Shabnam Dadgostar, and Ignacio Rey-Stolle

Subjects
Silicon, Materials science, business.industry, Germanium, Triple junction, Germanio, chemistry.chemical_element, Multijunction photovoltaic cell, Silicio, Células fotovoltaicas multiunión, chemistry, Optoelectronics, Multijunction solar cells, business, Absorption (electromagnetic radiation), Porosity, Layer (electronics), Deposition (law)
Abstract

Producción Científica, Virtual Ge substrates fabricated by direct deposition of Ge on Si have become a pathway with high potential to attain high-efficiency III-V multijunction solar cells on Si. We study the development of III-V triple junction solar cells using two types of Ge|Si virtual substrates. The first uses a thick (2-5 μm) Ge layer grown by CVD, which acts as the bottom Ge subcell. The second, grown by low-temperature RT-PECVD, has a thickness of a few tens of nanometres, with the Si substrate acting as Si bottom cell. We discuss the challenges related to each design (formation of cracks, parasitic absorption in the Ge layer, dislocations, ...), present the theoretical design and show the experimental results obtained. Finally, an advanced approach using embedded porous Si layers as buffer layers for crack mitigation is also presented., Ministerio de Ciencia, Innovación y Universidades (project RTI2018-094291-B-I00), Comunidad de Madrid (project S2018/EMT-4308), Ministerio de Ciencia e Innovación (grant PRE2019-088437), Junta de Castilla y León - Fondo Europeo de Desarrollo Regional (project VA283P18)

Published
2021
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22. The Map3k12 (Dlk)/JNK3 signaling pathway is required for pancreatic beta-cell proliferation during postnatal development

Author

Mathie Tenenbaum, Amar Abderrahmani, Amélie Bonnefond, Stéphane Dalle, Julien Bourry, Valery Gmyr, Philippe Froguel, Valérie Pawlowski, Nicole Beeler, Valérie Plaisance, Raphael Boutry, Hélène Ezanno, Clara Sanchez-Parra, Cécile Jacovetti, Romano Regazzi, Gianni Pasquetti, François Pattou, Syu-Ichi Hirai, Julie Kerr-Conte, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), 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 National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), NanoBioInterfaces - IEMN (NBI - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université de Lausanne = University of Lausanne (UNIL), Recherche translationnelle sur le diabète - U 1190 (RTD), 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), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Wakayama University, Imperial College London, This work was supported by grants from 'Société Francophone du Diabète (SFD)', 'European Genomic Institute for Diabetes' (E.G.I.D., ANR-10-LABEX-46) and European Commission, European Research Council (GEPIDIAB 294785 to P.F.), and by a grant from the Swiss National Science Foundation (310030-169480 to RR). Human islets were provided by the European Consortium for Islet Transplantation, funded by the Juvenile Diabetes Research Foundation International., ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), European Project: 294785,EC:FP7:ERC,ERC-2011-ADG_20110310,GEPIDIAB(2012), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Université de Lausanne (UNIL), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MAPK/ERK pathway, endocrine system, Biology, Mapk, Beta-cell mass, Transcriptome, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, [SPI]Engineering Sciences [physics], Mitogen-Activated Protein Kinase 10, Pregnancy, Insulin-Secreting Cells, Animals, Cell Proliferation/drug effects, Cyclin D1/genetics, Cyclin D1/metabolism, Cyclin D2/genetics, Cyclin D2/metabolism, Female, Glucose/pharmacology, Humans, Insulin/metabolism, Insulin-Secreting Cells/cytology, Insulin-Secreting Cells/metabolism, MAP Kinase Kinase Kinases/antagonists & inhibitors, MAP Kinase Kinase Kinases/genetics, MAP Kinase Kinase Kinases/metabolism, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 10/antagonists & inhibitors, Mitogen-Activated Protein Kinase 10/genetics, Mitogen-Activated Protein Kinase 10/metabolism, Obesity/metabolism, Obesity/pathology, Pancreas/growth & development, Pancreas/metabolism, RNA Interference, RNA, Small Interfering/metabolism, Rats, Signal Transduction/drug effects, Obesity, Postnatal development, Gene silencing, Cyclin D2, Insulin, Cyclin D1, RNA, Small Interfering, Molecular Biology, Pancreas, Cyclin, Cell Proliferation, Pharmacology, Serine/threonine-specific protein kinase, 0303 health sciences, geography, geography.geographical_feature_category, Kinase, 030302 biochemistry & molecular biology, Cell Biology, Islet, MAP Kinase Kinase Kinases, Cell biology, Glucose, Molecular Medicine, Signal transduction, Signal Transduction
Abstract

International audience; Unveiling the key pathways underlying postnatal beta-cell proliferation can be instrumental to decipher the mechanisms of beta-cell mass plasticity to increased physiological demand of insulin during weight gain and pregnancy. Using transcriptome and global Serine Threonine Kinase activity (STK) analyses of islets from newborn (10 days old) and adult rats, we found that highly proliferative neonatal rat islet cells display a substantially elevated activity of the mitogen activated protein 3 kinase 12, also called dual leucine zipper-bearing kinase (Dlk). As a key upstream component of the c-Jun amino terminal kinase (Jnk) pathway, Dlk overexpression was associated with increased Jnk3 activity and was mainly localized in the beta-cell cytoplasm. We provide the evidence that Dlk associates with and activates Jnk3, and that this cascade stimu- lates the expression of Ccnd1 and Ccnd2, two essential cyclins controlling postnatal beta-cell replication. Silencing of Dlk or of Jnk3 in neonatal islet cells dramatically hampered primary beta-cell replication and the expression of the two cyclins. Moreover, the expression of Dlk, Jnk3, Ccnd1 and Ccnd2 was induced in high replicative islet beta cells from ob/ob mice during weight gain, and from pregnant female rats. In human islets from non-diabetic obese individuals, DLK expression was also cytoplasmic and the rise of the mRNA level was associated with an increase of JNK3, CCND1 and CCND2 mRNA levels, when compared to islets from lean and obese patients with diabetes. In conclusion, we fjnd that activation of Jnk3 signalling by Dlk could be a key mechanism for adapting islet beta-cell mass during postnatal development and weight gain.

Published
2021
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23. Prevention of severe COVID-19 in the elderly by early high-titer plasma

Author

Rocio Rodriguez, Mariano Girasolli, Viviana Dominguez, Valeria Fernandez Vina, Jorge Lantos, Florencia Nowogrodzki, Julian DeLuca, Sofia Lujan Laudanno, Clarisa Taffarel, Florencia Izetta, Maria del Carmen Nigro, Nicolás Kreplak, Fernando Alvez, Laura Oyarvide, Ivonne Ritou, Emmanuel Ezequiel Valls, Dario Raul Alvarez, Patricia Lesch, Indira Pichetto Olanda, Florencia De la Fuente, Camila Witteveen, Sebastian Esperante, Juan Rusconi, Sofia Sol Aranda, Juan Canela, Ricardo Valentini, Mauricio T. Caballero, Clara Sanchez Yanotti, Paula Fernandez Estrella, Gisela Caruso, Patricia Rearte Carvalho, Ramiro Manuel Larrea, Candela Etchegaray, Romina Libster, Cecilia Pampuro, Fernando P. Polack, Jose L Scapellato, Micaela Piani, Julieta Alfonso, Daniela Carolina Galnarez, Maria Eugenia Macaneo, Federico Dimase, Agustina Venditti, Juan Molinos, Cristina Soler Riera, Jimena Ochoa, Luz Gibbons, Eduardo Perez, Rocio Zarlenga, Alejandra Hintze, Guido Ochoa, Damian Alvarez Paggi, Silvina Kuperman, Virginia Braem, Mariano Aizpurua, Alfonso Raggio, Miguel Santiago Gonzalez, Maria Teresa Paniguetti, Maria Fernanda Caracciolo, Gabriela Lescano, Juan Mauricio Vargas, Silvina Coviello, Fernando Althabe, Sofia Jarez Baglivo, Juan Sebastian Riera, Anibal Rondan, Mario Rovere, Gaston Pellegrino, Nicolas Itcovici, Yanina Miragaya, Alejandra Neira, Carla Marchionatti, Silvana Marquez, Maria Emilia Gutierrez Meyer, Gonzalo Pérez Marc, Marcela Balduzzi, Lia Pocket, Mabel Berrueta, Romina Zadoff, Noelia Iraizos, Susana Villaroel, Eduardo Bergel, Rocio Lopez Castelo, Maria Veronica Paz, Maria Dolores Silveyra, Maximiliano de Zan, Agostina Pagella, Lucila DiNunzio, Jimena Franco, Romina Militerno, Natalia Garcia Escude, Gabriela Leberzstein, Diego Wappner, Pablo Cruz, Romina Romero, Jorge Geffner, Susana Pastor Arguello, Leonel Langellotti, Andrea V. Gamarnik, Alejandra Debonis, Ignacio Esteban, Gaston Ofman, Federico Cesar Etchenique, Cristian Wood, Ivonne Name, Natali Estrada, Sebastian Perez Marc, Enio Garcia, Sofia Rapelius, Alvaro Ciganda, Alejandra Bianchi, and Adrian Ferretti

Subjects
medicine.medical_specialty, Randomization, Respiratory rate, business.industry, Respiratory disease, Placebo, medicine.disease, Titer, Internal medicine, Number needed to treat, Clinical endpoint, Medicine, business, Adverse effect
Abstract

BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression.MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate ≥30 and/or an O2satResults160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%.A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed.ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives.Funded by The Bill & Melinda Gates Foundation and The Fundación INFANT Pandemic Fund. Registered in the Dirección de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163).All authors have completed the ICMJE uniform disclosure form atwww.icmje.org/coi_disclosure.pdfand declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

Published
2020
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24. Stability and peri-implant bone level of post-extractive implants in elderly patients

Author

Orlando Guerra Cobian, Clara Sanchez Silot, and Jorge Luis García Romero

Subjects
lcsh:R5-920, lcsh:Public aspects of medicine, implantes postextractivos, estabilidad, pérdida ósea periimplantaria, adulto mayor, lcsh:RA1-1270, lcsh:Medicine (General)
Abstract

Introduction: Post-extractive implants shorten the time in achieving the rehabilitation of the patient, being this condition an essential factor to restore the quality of life to elderly patients at short term.Objective: To determine the stability values and peri-implant bone loss in post-extractive implants in elderly patients.Material and Method: A cohort study was carried out in 99 elderly patients at Raúl González Sánchez Dental School of Havana from 2017 to 2019. Under the consent of the patients, 173 post-extractive implants were placed. Bone support type, and primary and secondary stability were determined on the basis of a resonance frequency analysis with Ostell Mentor®. The peri-implant bone level and peri-implant bone loss were measured until 12 months after rehabilitation.Results: Implants were mainly positioned in the maxillary incisive site in 43,3 % of the cases. The average values of primary and secondary stability were 48 ISQ and 68 ISQ, respectively. The average bone loss after 12 months of rehabilitation was 1,04 ± 0,22 mm.Conclusions: Post-extractive dental implants were inserted preferably in the maxillary incisive site and in D2 bone type, registering moderated average values of primary stability and substantial average values of secondary stability. The peri-implant vertical bone loss exhibited implants with similar values than those in the healed areas and within the standardized value for peri-implant bone loss within the first year after implant placement.

Published
2020

26. Precursors for Atmospheric Plasma-Enhanced Sintering: Low-Temperature Inkjet Printing of Conductive Copper

Author

Shreya Mrig, Caroline E. Knapp, Samuel P. Douglas, Patrick Choquet, Clara Sanchez-Perez, Elizabeth A. Metcalf, and Nicolas D. Boscher

Subjects
Thermogravimetric analysis, Denticity, Materials science, plasma-assisted inkjet printing, chemistry.chemical_element, Sintering, Infrared spectroscopy, 02 engineering and technology, 01 natural sciences, chemistry.chemical_compound, Diamine, 0103 physical sciences, 010302 applied physics, inkjet printing, Full Paper, Thermal decomposition, General Chemistry, Full Papers, 021001 nanoscience & nanotechnology, Copper, chemistry, conductive copper, Elemental analysis, Physical chemistry, atmospheric plasma, 0210 nano-technology, copper precursors
Abstract

Bidentate diamine and amino‐alcohol ligands have been used to form solid, water‐soluble, and air‐stable monomeric copper complexes of the type [Cu(NH2CH2CH(R)Y)2(NO3)2] (1, R=H, Y=NH2; 2, R=H, Y=OH; 3, R=Me, Y=OH). The complexes were characterized by elemental analysis, mass spectrometry, infrared spectroscopy, thermal gravimetric analysis, and single‐crystal X‐ray diffraction. Irrespective of their decomposition temperature, precursors 1–3 yield highly conductive copper features [1.5×10−6 Ω m (±5×10−7 Ω m)] upon atmospheric‐pressure plasma‐enhanced sintering.

Published
2018
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27. Different polarization and functionality of CD4+ T helper subsets in people with post-COVID condition

Author

Clara Sánchez-Menéndez, Olivia de la Calle-Jiménez, Elena Mateos, Lorena Vigón, Daniel Fuertes, María Aranzazu Murciano Antón, Esther San José, Valentín García-Gutiérrez, Miguel Cervero, Montserrat Torres, and Mayte Coiras

Subjects
post-covid condition, CD4+ T cells, T helper polarization, cytokines, Th1, Th2, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionAfter mild COVID-19 that does not require hospitalization, some individuals develop persistent symptoms that may worsen over time, producing a multisystemic condition termed Post-COVID condition (PCC). Among other disorders, PCC is characterized by persistent changes in the immune system that may not be solved several months after COVID-19 diagnosis.MethodsPeople with PCC were recruited to determine the distribution and functionality of CD4+ T helper (Th) subsets in comparison with individuals with mild, severe, and critical presentations of acute COVID-19 to evaluate their contribution as risk or protective factors for PCC.ResultsPeople with PCC showed low levels of Th1 cells, similar to individuals with severe and critical COVID-19, although these cells presented a higher capacity to express IFNγ in response to stimulation. Th2/Th1 correlation was negative in individuals with acute forms of COVID-19, but there was no significant Th2/Th1 correlation in people with PCC. Th2 cells from people with PCC presented high capacity to express IL-4 and IL-13, which are related to low ventilation and death associated with COVID-19. Levels of proinflammatory Th9 and Th17 subsets were significantly higher in people with PCC in comparison with acute COVID-19, being Th1/Th9 correlation negative in these individuals, which probably contributed to a more pro-inflammatory than antiviral scenario. Th17 cells from approximately 50% of individuals with PCC had no capacity to express IL-17A and IL-22, similar to individuals with critical COVID-19, which would prevent clearing extracellular pathogens. Th2/Th17 correlation was positive in people with PCC, which in the absence of negative Th1/Th2 correlation could also contribute to the proinflammatory state. Finally, Th22 cells from most individuals with PCC had no capacity to express IL-13 or IL-22, which could increase tendency to reinfections due to impaired epithelial regeneration.DiscussionPeople with PCC showed skewed polarization of CD4+ Th subsets with altered functionality that was more similar to individuals with severe and critical presentations of acute COVID-19 than to people who fully recovered from mild disease. New strategies aimed at reprogramming the immune response and redirecting CD4+ Th cell polarization may be necessary to reduce the proinflammatory environment characteristic of PCC.

Published
2024
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28. RSV Lower Respiratory Tract Illness in Infants of Low- and Middle-income Countries

Author

Clara Sanchez Yanotti, Sofia Lujan Laudanno, and Fernando P. Polack

Subjects
Palivizumab, Pediatrics, medicine.medical_specialty, Developing country, Severe disease, Respiratory Syncytial Virus Infections, Antiviral Agents, Drug Costs, Young infants, Global Burden of Disease, medicine, Bronchiolitis, Viral, Humans, Developing Countries, business.industry, Coinfection, Mortality rate, General Medicine, Pneumonia, Asthma, Hospitalization, medicine.anatomical_structure, Low and middle income countries, business, Developed country, Infant, Premature, Respiratory tract, medicine.drug
Abstract

This review addresses differences in respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) between industrial- ized and developing countries and provides observations associated with the dissimilar consequences of viral infection in both environments. RSV LRTI is an important cause of morbidity and mortality in infants worldwide. Its burden is highest in de- veloping countries, where most hospitalizations and mortality occur. Palivizumab has been approved for disease prevention in premature infants in numerous countries but its cost and requirement for several doses hampers its routine use. The significant gap between low- and high-income countries in mortality rates stresses the need to identify specific risk factors for RSV LRTI prevention in different populations.Conclusion. RSV LTRI continues to be a serious problem for industrialised and developing countries, although mortality occurs preferentially in the latter. Several vaccines and monoclonal antibodies to prevent severe disease are advancing steadily in late phase trials. The next decade may witness a change in the landscape of RSV infections in young infants.

Published
2020

29. Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers

Author

Rocio Eiros, Oihane Perez-Escurza, Pedro L. Sánchez, Clara Sanchez-Pablo, Laura Macias-Alvarez, Manuel Barreiro-Pérez, Elena Díaz-Peláez, Alba Torres-Valle, Soraya Merchán, Inés Toranzo, David González-Calle, Quentin Lecrevisse, Alba Pérez-Pons, Guillermo Oliva-Ariza, Alberto Orfao, Eduardo Villacorta, Julia Almeida, Rafael Fluxa, Ana Martín-García, José L. Bravo-Grandez, Blanca Fuentes-Herrero, Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España), Centro de Investigación Biomédica en Red Cáncer (España), Instituto de Salud Carlos III, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Eiros, Rocío [0000-0002-9488-2555], Barreiro-Pérez, Manuel [0000-0001-7489-2935], Pérez-Pons, Alba [0000-0002-5805-1391], Torres-Valle, Alba [0000-0002-9485-5696], Sanchez-Pablo, Clara [0000-0002-7656-7156], Gonzalez-Calle, David [0000-0001-9051-0124], Perez-Escurza, Oihane [0000-0002-6966-4337], Fuentes-Herrero, Blanca [0000-0002-4038-8439], Orfao, Alberto [0000-0002-0007-7230], Sánchez, Pedro L. [0000-0002-1402-0526], Eiros, Rocío, Barreiro-Pérez, Manuel, Pérez-Pons, Alba, Torres-Valle, Alba, Sanchez-Pablo, Clara, Gonzalez-Calle, David, Perez-Escurza, Oihane, Fuentes-Herrero, Blanca, Orfao, Alberto, and Sánchez, Pedro L.

Subjects
medicine.medical_specialty, Myocarditis, business.industry, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), fungi, medicine.disease, respiratory tract diseases, body regions, Pericarditis, Internal medicine, Health care, medicine, Descriptive research, skin and connective tissue diseases, business
Abstract

Background: Cardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection., Methods We studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR) imaging. Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria., Results: Median age was 52 years (IQR 41-57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3-11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p, Conclusions: Pericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response., This study was supported by CIBERCV (CB16/11/00374), CIBERONC (CB16/12/00400) and the COV20/00386 grant from the Instituto de Salud Carlos III and FEDER, Ministerio de Ciencia e Innovacion, Madrid, Spain.

Published
2020

30. T2 Mapping Identifies Early Anthracycline-Induced Cardiotoxicity in Elderly Patients With Cancer

Author

Carlos Galán-Arriola, Clara Sanchez-Pablo, Ana Martín-García, Pedro L. Sánchez, Guillermo Macias de Plasencia, Elena Díaz-Peláez, Juan Jesus Cruz, Javier Sánchez-González, Borja Ibanez, and Lucia Lopez-Corral

Subjects
medicine.medical_specialty, T2 mapping, 030204 cardiovascular system & hematology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Neoplasms, medicine, Humans, Radiology, Nuclear Medicine and imaging, Anthracyclines, cardiovascular diseases, Anthracycline induced cardiotoxicity, Aged, Cardiotoxicity, Ejection fraction, Antibiotics, Antineoplastic, business.industry, Late stage, Cancer, medicine.disease, cardiovascular system, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract

Current measures of anthracycline-induced cardiotoxicity, defined by decreases in left ventricular ejection fraction (LVEF), may become apparent only at a late stage when the myocardium has been significantly damaged, exceeding its ability to compensate ([1][1]). Our group has recently shown in a

Published
2019

31. Pre-existing cell populations with cytotoxic activity against SARS-CoV-2 in people with HIV and normal CD4/CD8 ratio previously unexposed to the virus

Author

Guiomar Casado-Fernández, Juan Cantón, Laura Nasarre, Fernando Ramos-Martín, Mario Manzanares, Clara Sánchez-Menéndez, Daniel Fuertes, Elena Mateos, María Aranzazu Murciano-Antón, Mayte Pérez-Olmeda, Miguel Cervero, Montserrat Torres, Rafael Rodríguez-Rosado, and Mayte Coiras

Subjects
people with HIV, COVID-19 vaccination, Tγδ cells, cellular immune response, humoral immune response, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionHIV-1 infection may produce a detrimental effect on the immune response. Early start of antiretroviral therapy (ART) is recommended to preserve the integrity of the immune system. In fact, people with HIV (PWH) and normal CD4/CD8 ratio appear not to be more susceptible to severe forms of COVID-19 than the general population and they usually present a good seroconversion rate in response to vaccination against SARS-CoV-2. However, few studies have fully characterized the development of cytotoxic immune populations in response to COVID-19 vaccination in these individuals.MethodsIn this study, we recruited PWH with median time of HIV-1 infection of 6 years, median CD4/CD8 ratio of 1.0, good adherence to ART, persistently undetectable viral load, and negative serology against SARS-CoV-2, who then received the complete vaccination schedule against COVID-19. Blood samples were taken before vaccination against COVID-19 and one month after receiving the complete vaccination schedule. ResultsPWH produced high levels of IgG against SARS-CoV-2 in response to vaccination that were comparable to healthy donors, with a significantly higher neutralization capacity. Interestingly, the cytotoxic activity of PBMCs from PWH against SARS-CoV-2-infected cells was higher than healthy donors before receiving the vaccination schedule, pointing out the pre-existence of activated cell populations with likely unspecific antiviral activity. The characterization of these cytotoxic cell populations revealed high levels of Tgd cells with degranulation capacity against SARS-CoV-2-infected cells. In response to vaccination, the degranulation capacity of CD8+ T cells also increased in PWH but not in healthy donors.DiscussionThe full vaccination schedule against COVID-19 did not modify the ability to respond against HIV-1-infected cells in PWH and these individuals did not show more susceptibility to breakthrough infection with SARS-CoV-2 than healthy donors after 12 months of follow-up. These results revealed the development of protective cell populations with broad-spectrum antiviral activity in PWH with normal CD4/CD8 ratio and confirmed the importance of early ART and treatment adherence to avoid immune dysfunctions.

Published
2024
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32. Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries

Author

Mark Jit, Quique Bassat, Joy E Lawn, Farah Seedat, Erzsébet Horváth-Puhó, Bronner P Gonçalves, Amina Abubakar, Ziyaad Dangor, Proma Paul, Simon R Procter, Hima B John, Shannon Leahy, Sridhar Santhanam, Celine Aerts, Carophine Nasambu, Romina Libster, Clara Sánchez Yanotti, and Jaya Chanda

Subjects
Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract

Introduction There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa.Methods Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data.Results 161 iGBS-exposed and 439 unexposed children and young adults (age 1–20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$−1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04–0.13 vs 0.06, 0.02–0.10).Conclusion The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Published
2024
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33. Contribution of the Long Noncoding RNA H19 to β-Cell Mass Expansion in Neonatal and Adult Rodents

Author

Claudiane Guay, Cécile Jacovetti, Olivier Dumortier, Romano Regazzi, Marc Prentki, Kailun Lee, Clara Sanchez-Parra, D. Ross Laybutt, Marie Line Peyot, and Emmanuel Van Obberghen

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Offspring, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Biology, Cell Line, Rats, Sprague-Dawley, 03 medical and health sciences, Insulin resistance, Insulin-Secreting Cells, Diabetes mellitus, Internal medicine, microRNA, Internal Medicine, medicine, Animals, Glucose homeostasis, Cell Proliferation, Cell Death, Gene Expression Profiling, Insulin, Pancreatic islets, RNA, medicine.disease, Rats, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Cell Death/physiology, Cell Proliferation/physiology, Insulin-Secreting Cells/metabolism, Proto-Oncogene Proteins c-akt/metabolism, RNA, Long Noncoding/genetics, RNA, Long Noncoding/metabolism, RNA, Long Noncoding, Proto-Oncogene Proteins c-akt
Abstract

Pancreatic β-cell expansion throughout the neonatal period is essential to generate the appropriate mass of insulin-secreting cells required to maintain blood glucose homeostasis later in life. Hence, defects in this process can predispose to diabetes development during adulthood. Global profiling of transcripts in pancreatic islets of newborn and adult rats revealed that the transcription factor E2F1 controls expression of the long noncoding RNA H19, which is profoundly downregulated during the postnatal period. H19 silencing decreased β-cell expansion in newborns, whereas its re-expression promoted proliferation of β-cells in adults via a mechanism involving the microRNA let-7 and the activation of Akt. The offspring of rats fed a low-protein diet during gestation and lactation display a small β-cell mass and an increased risk of developing diabetes during adulthood. We found that the islets of newborn rats born to dams fed a low-protein diet express lower levels of H19 than those born to dams that did not eat a low-protein diet. Moreover, we observed that H19 expression increases in islets of obese mice under conditions of increased insulin demand. Our data suggest that the long noncoding RNA H19 plays an important role in postnatal β-cell mass expansion in rats and contributes to the mechanisms compensating for insulin resistance in obesity.

Published
2018

36. Chalcogen–chalcogen secondary bonding interactions in trichalcogenaferrocenophanes

Author

Clara Sanchez-Perez, Risto S. Laitinen, J. Mikko Rautiainen, Minna M. Karjalainen, and Raija Oilunkaniemi

Subjects
010405 organic chemistry, Intermolecular force, chemistry.chemical_element, General Chemistry, Crystal structure, 010402 general chemistry, Condensed Matter Physics, 01 natural sciences, Sulfur, 0104 chemical sciences, Chalcogen, Crystallography, chemistry, General Materials Science, Tellurium, Selenium, Secondary bonding, Natural bond orbital
Abstract

The solid-state structures of all members in the series of trichalcogenaferrocenophanes [Fe(C5H4E)2E′] (E, E′ = S, Se, Te) (1–9) have been explored to understand the trends in secondary bonding interactions (SBIs) between chalcogen elements sulfur, selenium, and tellurium. To complete the series, the crystal structures of the four hitherto unknown complexes [Fe(C5H4S)2Te] (3), [Fe(C5H4Se)2S] (4), [Fe(C5H4Se)2Te] (6), and [Fe(C5H4Te)2S] (7) have been determined in this contribution. The packings of all complexes 1–9 were considered by DFT calculations at the PBE0/pob-TZVP level of theory using periodic boundary conditions. The intermolecular close contacts were considered by QTAIM and NBO analyses. The isomorphous complexes [Fe(C5H4S)2S] (1), [Fe(C5H4S)2Se] (2), and [Fe(C5H4Se)2Se] (5a) form dimers via weak interactions between the central chalcogen atoms of the two trichalcogena chains of adjacent complexes. In the second isomorphous series consisting of [Fe(C5H4Se)2S] (4) and 5b, the complexes are linked together into continuous chains by short contacts via the terminal selenium atoms. The intermolecular chalcogen–chalcogen interactions are significantly stronger in complexes [Fe(C5H4S)2Te] (3), [Fe(C5H4Se)2Te] (6), and [Fe(C5H4Te)2E′] (E′ = S, Se, Te) (7–9), which contain tellurium. The NBO comparison of donor–acceptor interactions in the lattices of [Fe(C5H4S)2S] (1), [Fe(C5H4Se)2Se] (5a and 5b), and [Fe(C5H4Te)2Te] (9) indeed shows that the n(5pTe)2 → σ*(Te–Te) interactions in 9 are the strongest. All other interaction energies are significantly smaller even in the case of tellurium. The computed natural charges of the chalcogen atoms indicate that electrostatic effects strengthen the attractive interactions in the case of all chalcogen atoms.

Published
2016
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37. Macrocycles containing 1,1’-ferrocenyldiselenolato ligands on group 4 metallocenes

Author

Raija Oilunkaniemi, Risto S. Laitinen, Claire J. Carmalt, Clara Sanchez-Perez, Minna M. Karjalainen, and Caroline E. Knapp

Subjects
Diffraction, Thermogravimetric analysis, chemistry.chemical_element, 02 engineering and technology, Crystal structure, Nuclear magnetic resonance spectroscopy, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Decomposition, 0104 chemical sciences, Inorganic Chemistry, Crystallography, chemistry, Group (periodic table), 0210 nano-technology, Selenium
Abstract

Macrocyclic [Fe(η⁵-C₅H₄Se)₂M(η⁵-C₅H₄R)₂]₂ [M = Ti (1), Zr (2), Hf (3), R = H; and M = Zr (4), Hf (5), R = tBu] were prepared and characterized by ⁷⁷Se NMR spectroscopy and the crystal structures of 1–3 and 5 were determined by single-crystal X-ray diffraction. The crystal structure of 4 is known and the complex is isomorphous with 5. 1–5 form mutually similar macrocyclic tetranuclear complexes in which the alternating Fe(C₅H₄Se)₂ and M(C₅H₄R)₂ centers are linked by selenium bridges. The thermogravimetric analysis (TGA) of 1–3 under a helium atmosphere indicated that the complexes undergo a two-step decomposition upon heating. The final products were identified using powder X-ray diffraction as FexMSe₂, indicating their potential as single-source precursors for functional materials.

Published
2018

38. Sucrose-induced Receptor Kinase SIRK1 Regulates a Plasma Membrane Aquaporin in Arabidopsis

Author

Heidi Pertl-Obermeyer, Waltraud X. Schulze, Xu Na Wu, Clara Sanchez Rodriguez, and Gerhard Obermeyer

Subjects
Sucrose, biology, Arabidopsis Proteins, Kinase, Research, Recombinant Fusion Proteins, Cell Membrane, Green Fluorescent Proteins, Cyclin-dependent kinase 2, Arabidopsis, Aquaporin, Aquaporins, Biochemistry, Analytical Chemistry, MAP2K7, Cell biology, Membrane protein, biology.protein, Phosphorylation, ASK1, Protein kinase A, Protein Kinases, Molecular Biology
Abstract

The transmembrane receptor kinase family is the largest protein kinase family in Arabidopsis, and it contains the highest fraction of proteins with yet uncharacterized functions. Here, we present functions of SIRK1, a receptor kinase that was previously identified with rapid transient phosphorylation after sucrose resupply to sucrose-starved seedlings. SIRK1 was found to be an active kinase with increasing activity in the presence of an external sucrose supply. In sirk1 T-DNA insertional mutants, the sucrose-induced phosphorylation patterns of several membrane proteins were strongly reduced; in particular, pore-gating phosphorylation sites in aquaporins were affected. SIRK1-GFP fusions were found to directly interact with aquaporins in affinity pull-down experiments on microsomal membrane vesicles. Furthermore, protoplast swelling assays of sirk1 mutants and SIRK1-GFP expressing lines confirmed a direct functional interaction of receptor kinase SIRK1 and aquaporins as substrates for phosphorylation. A lack of SIRK1 expression resulted in the failure of mutant protoplasts to control water channel activity upon changes in external sucrose concentrations. We propose that SIRK1 is involved in the regulation of sucrose-specific osmotic responses through direct interaction with and activation of an aquaporin via phosphorylation and that the duration of this response is controlled by phosphorylation-dependent receptor internalization.

Published
2013
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40. SALMANTICOR study. Rationale and design of a population-based study to identify structural heart disease abnormalities: a spatial and machine learning analysis

Author

Aitor Uribarri, Beatriz Garde, Víctor Vicente-Palacios, Baltasara Blazquez, Elena Díaz-Peláez, Alfonso Romero, Javier Jiménez-Candil, Clara Sanchez-Pablo, Jose Manuel Hernandez, Pedro L. Sánchez, Ana Martín-García, Pedro Pablo Vara, Manuel Barreiro-Pérez, Jose Ignacio Melero-Alegria, Fernando Perez-Escanilla, P. Ignacio Dorado-Díaz, Inmaculada Santolino, Manuel Cascon, Jose Maria de Dios, Sara Cascon, Paz Muriel, Jesus Hernandez-Hernandez, Ignacio Cruz-González, and Maria Concepcion Ledesma

Subjects
Male, Heart disease, Epidemiology, population, computer.software_genre, Regional policy, Machine Learning, 0302 clinical medicine, Risk Factors, Informed consent, enfermedades cardíacas, Surveys and Questionnaires, Health care, Prevalence, Protocol, Rural, Prospective Studies, 030212 general & internal medicine, education.field_of_study, Incidence, General Medicine, Middle Aged, Geography, Research Design, Instituto de Investigación Biomédica de Salamanca (IBSAL), Female, Social status, Adult, medicine.medical_specialty, Adolescent, Heart Diseases, spatial analysis, Population, 3205.01 Cardiología, Structural heart diseas, Machine learning, Young Adult, 03 medical and health sciences, medicine, Urban, Humans, education, Aged, business.industry, Public health, Spatial analysis, medicine.disease, structural heart disease, Cross-Sectional Studies, Spain, Residence, rural, Artificial intelligence, business, urban, computer, 030217 neurology & neurosurgery
Abstract

IntroductionThis study aims to obtain data on the prevalence and incidence of structural heart disease in a population setting and, to analyse and present those data on the application of spatial and machine learning methods that, although known to geography and statistics, need to become used for healthcare research and for political commitment to obtain resources and support effective public health programme implementation.Methods and analysisWe will perform a cross-sectional survey of randomly selected residents of Salamanca (Spain). 2400 individuals stratified by age and sex and by place of residence (rural and urban) will be studied. The variables to analyse will be obtained from the clinical history, different surveys including social status, Mediterranean diet, functional capacity, ECG, echocardiogram, VASERA and biochemical as well as genetic analysis.Ethics and disseminationThe study has been approved by the ethical committee of the healthcare community. All study participants will sign an informed consent for participation in the study. The results of this study will allow the understanding of the relationship between the different influencing factors and their relative importance weights in the development of structural heart disease. For the first time, a detailed cardiovascular map showing the spatial distribution and a predictive machine learning system of different structural heart diseases and associated risk factors will be created and will be used as a regional policy to establish effective public health programmes to fight heart disease. At least 10 publications in the first-quartile scientific journals are planned.Trial registration numberNCT03429452.

Published
2019
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41. Cover Feature: Precursors for Atmospheric Plasma-Enhanced Sintering: Low-Temperature Inkjet Printing of Conductive Copper (ChemistryOpen 11/2018)

Author

Patrick Choquet, Samuel P. Douglas, Nicolas D. Boscher, Shreya Mrig, Elizabeth A. Metcalf, Caroline E. Knapp, and Clara Sanchez-Perez

Subjects
inkjet printing, Materials science, business.industry, Cover Pictures, plasma-assisted inkjet printing, Sintering, chemistry.chemical_element, Atmospheric-pressure plasma, General Chemistry, Copper, chemistry, conductive copper, Feature (computer vision), Cover Picture, Optoelectronics, Cover (algebra), atmospheric plasma, business, Electrical conductor, Inkjet printing, copper precursors
Abstract

The Cover Feature shows bidentate diamine and amino‐alcohol ligands, which are used to form solid, water‐soluble, and air‐stable monomeric copper complexes for low‐temperature plasma‐assisted inkjet printing of conductive copper. More information can be found in the Full Paper by C. E. Knapp et al. on page 850 in Issue 11, 2018 (DOI: https://doi.org/10.1002/open.201800131).

Published
2018
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42. PB2159: CHARACTERIZATION OF THE IMMUNE RESPONSE DEVELOPED IN PATIENTS WITH MULTIPLE MYELOMA AFTER RECEIVING TWO DOSES OF THE VACCINE AGAINST SARS-COV-2

Author

Laura Perez, Miriam Solera, Magdalena Corona, Montserrat Torres, Guiomar Casado, Clara Sánchez-Menéndez, Alejandro Zurdo, Javier Garcia, Maria Aranzazu Murciano, Maria Teresa Pérez, Valentin Garcia Gutierrez, Maria Teresa Coiras, and Sara Rodríguez Mora

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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43. PB1944: INDIVIDUALS WITH CHRONIC LYMPHOCYTIC LEUKAEMIA SHOW IMPAIRED HUMORAL BUT NORMAL CELLULAR IMMUNE RESPONSES AFTER RECEIVING A COMPLETE VACCINATION SCHEDULE AGAINST SARS-COV-2

Author

Clara Sánchez-Menéndez, Magdalena Corona, Alejandro Zurdo, Alicia Simón-Rueda, Elena Mateos, Mario Manzanares, Javier García-Pérez, Mayte Pérez-Olmeda, Sara Rodríguez-Mora, María Aránzazu Murciano-Antón, Valentín García-Gutiérrez, Mayte Coiras, and Montserrat Torres

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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44. ERECTA receptor-like kinase and heterotrimeric G protein from Arabidopsis are required for resistance to the necrotrophic fungus Plectosphaerella cucumerina

Author

Clara Sanchez-Rodriguez, ANTONIO MOLINA FERNANDEZ, Francisco Llorente, Clara Sánchez-Rodríguez, Lucia Jordá, and Carlos Alonso-Blanco

Subjects
Genetics, food.ingredient, biology, G protein, Jasmonic acid, fungi, Mutant, Cell Biology, Plant Science, Heterotrimeric G-protein complex, biology.organism_classification, chemistry.chemical_compound, food, Plectosphaerella, chemistry, Heterotrimeric G protein, Arabidopsis, Botrytis
Abstract

Arabidopsis resistance to the necrotrophic fungus Plectosphaerella cucumerina is complex and depends on the ethylene, jasmonic acid and salicylic acid signaling pathways. A quantitative trait loci (QTL) analysis of resistance to this fungus was performed using two populations of recombinant inbred lines. Three loci QRP1-QRP3 (for Quantitative Resistance to Plectosphaerella) were identified and mapped on chromosome 2 (QRP1 and QRP2) and 5 (QRP3). QRP1, the locus showing the strongest effect, was found to correspond to the ERECTA (ER) gene that encodes a receptor-like-kinase (RLK), which has been previously implicated in plant development, and resistance to the bacterium Ralstonia solanacearum. The leucine-rich repeat and the kinase domains of ERECTA were specifically required for resistance to P. cucumerina, as er mutant alleles impaired in any of these domains showed enhanced susceptibility to this fungus, but not to other virulent pathogens. The involvement of the ER-signaling pathway in resistance to P. cucumerina was supported by the fact that three mutants defective in this pathway, elk2, elk5 and elk4 (agb1-1), which encodes the beta-subunit of Arabidopsis heterotrimeric G protein, were also impaired in their resistance to this fungus. The putative function of the Arabidopsis heterotrimeric G protein in resistance to P. cucumerina suggested by the enhanced susceptibility of agb1-1 was corroborated by the demonstration that a null allele (gpa1-4) of the G protein alpha-subunit showed enhanced resistance to this pathogen. Deposition of beta-1,3-glucan callose at infection sites was specifically impaired in er-1 and agb1-1 mutants upon P. cucumerina inoculation. Taken together, these data suggest a putative function of ERECTA and heterotrimeric G protein in P. cucumerina perception.

Published
2005
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45. Progression of posturographic findings after acquired brain injury

Author

Roberto Llorens, Nuria Navalón, Enrique Noé, B. Moliner, Carolina Colomer, J. Ferri, Clara Sanchez-Leiva, Gracia Martinez-Crespo, and Ignacio Verdecho

Subjects
Adult, Male, Balance, medicine.medical_specialty, Neuroscience (miscellaneous), Postural instability, Sensory interaction, Limits of stability, Assessment, Sensitivity and Specificity, Physical medicine and rehabilitation, Predictive Value of Tests, Assistive technology, Developmental and Educational Psychology, medicine, Humans, Evaluation, Acquired brain injury, Postural Balance, Physical Therapy Modalities, Balance (ability), Outcome, Measurement, business.industry, Reproducibility of Results, Middle Aged, Vestibular Function Tests, medicine.disease, Vestibular Evoked Myogenic Potentials, Cross-Sectional Studies, Balance performance, Spain, Brain Injuries, Physical therapy, Disease Progression, Female, Neurology (clinical), business, Psychomotor Performance, Follow-Up Studies
Abstract

Objective: To study the characteristics of balance performance in a sample of patients with increasing postural instability after acquired brain injury (ABI) and to establish the clinical utility of a new computerized posturographic system (NedSVE/IBV). Methods: This study included 108 patients with ABI divided into five groups from minimal to severe postural impairment. All patients were assessed with the NedSVE/IBV system and with traditional balance measures. Posturographic analyses included the modified clinical test of sensory interaction on balance, the limits of stability and the weight-shifting test. Sensitivity to detect changes and reproducibility were evaluated in 63 patients who were followed-up for 6 months and in 20 patients who were evaluated on two separate occasions during the same week, respectively. Results: The patients showed reduced stability limits, abnormal postural responses and an increased reliance on visual input with differences in intensity directly related to their degree of balance impairment. Posturographic study showed excellent convergent validity, reproducibility and sensitivity to detect changes. Conclusion: The data suggests that, regardless of the intensity of postural instability, there is a common mechanism of sensory processing to maintain balance after ABI. The NedSVE-IBV system is a valid tool to quantify balance after ABI.

Published
2014

46. Trophic Ecology during the Ontogenetic Development of the Pelagic Thresher Shark Alopias pelagicus in Baja California Sur, Mexico

Author

Clara Sánchez-Latorre, Felipe Galván-Magaña, Fernando R. Elorriaga-Verplancken, Arturo Tripp-Valdez, Rogelio González-Armas, Alejandra Piñón-Gimate, and Antonio Delgado-Huertas

Subjects
chemical ecology, stable isotopes, vertebrae, muscle, trophic shifts, Biology (General), QH301-705.5
Abstract

The trophic ecology of the Pelagic Thresher shark (Alopias pelagicus) was evaluated based on chemical ecology using stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) in the vertebrae and muscles. Individuals were caught between August 2013 and October 2019 on both the coasts of Baja California Sur, Mexico. In Bahía Tortugas, the mean vertebrae (n = 35) values were 12.72 ± 1.06‰ (δ15N) and −14.79 ± 0.61‰ (δ13C), while in muscles (n = 32) these values were 16.63 ± 0.76‰ (δ15N) and −17.18 ± 0.39‰ (δ13C). In Santa Rosalía, the mean vertebrae (n = 125) isotopic values were 14.4 ± 1.59‰ (δ15N) and −14.18 ± 0.51‰ (δ13C), while in muscles (n = 43), these values were 18.08 ± 0.96‰ (δ15N) and −16.43 ± 0.34‰ (δ13C). These results show higher δ15N values in Santa Rosalía as an effect of baseline isotopic differences between the two regions, whereas the δ13C values were lower in Bahía Tortugas, suggesting offshore ecological behavior (p < 0.05). In Santa Rosalía, there were significant differences by sex for δ15N in muscle, whereas the δ13C showed ontogenetic shifts, indicating that neonates feed in coastal areas more commonly than juveniles or adults (p < 0.05). Neither sex nor ontogenetic differences were observed in Bahía Tortugas (p > 0.05), suggesting a high overlap between their isotopic niches. Therefore, Alopias pelagicus uses the same ecological niche throughout its life, and there is consistency between sexes. The mean trophic position for both tissues and regions was 4.5, which corresponds to a tertiary predator, without any differences between stages or sex. Due to their higher energetic needs, juveniles and females showed the greatest isotopic niche amplitude; thus, their ecological niche is the widest.

Published
2023
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47. A primary cell wall cellulose-dependent defense mechanism against vascular pathogens revealed by time-resolved dual transcriptomics

Author

Alexandra Menna, Susanne Dora, Gloria Sancho-Andrés, Anurag Kashyap, Mukesh Kumar Meena, Kamil Sklodowski, Debora Gasperini, Nuria S. Coll, and Clara Sánchez-Rodríguez

Subjects
Arabidopsis, Fusarium oxysporum, Ralstonia solanacearum, plant-pathogen interaction, dual-time course transcriptomics, cellulose, Biology (General), QH301-705.5
Abstract

Abstract Background Cell walls (CWs) are protein-rich polysaccharide matrices essential for plant growth and environmental acclimation. The CW constitutes the first physical barrier as well as a primary source of nutrients for microbes interacting with plants, such as the vascular pathogen Fusarium oxysporum (Fo). Fo colonizes roots, advancing through the plant primary CWs towards the vasculature, where it grows causing devastation in many crops. The pathogenicity of Fo and other vascular microbes relies on their capacity to reach and colonize the xylem. However, little is known about the root-microbe interaction before the pathogen reaches the vasculature and the role of the plant CW during this process. Results Using the pathosystem Arabidopsis-Fo5176, we show dynamic transcriptional changes in both fungus and root during their interaction. One of the earliest plant responses to Fo5176 was the downregulation of primary CW synthesis genes. We observed enhanced resistance to Fo5176 in Arabidopsis mutants impaired in primary CW cellulose synthesis. We confirmed that Arabidopsis roots deposit lignin in response to Fo5176 infection, but we show that lignin-deficient mutants were as susceptible as wildtype plants to Fo5176. Genetic impairment of jasmonic acid biosynthesis and signaling did not alter Arabidopsis response to Fo5176, whereas impairment of ethylene signaling did increase vasculature colonization by Fo5176. Abolishing ethylene signaling attenuated the observed resistance while maintaining the dwarfism observed in primary CW cellulose-deficient mutants. Conclusions Our study provides significant insights on the dynamic root-vascular pathogen interaction at the transcriptome level and the vital role of primary CW cellulose during defense response to these pathogens. These findings represent an essential resource for the generation of plant resistance to Fo that can be transferred to other vascular pathosystems.

Published
2021
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48. Constrained Dynamic Matrix Control under International Electrotechnical Commission Standard 61499 and the Open Platform Communications Unified Architecture

Author

Sergio Bustos-Pulluquitin, Gustavo Caiza, Mayra Llumitasig-Galarza, Maritza Castro-Mayorga, Clara Sánchez-Benítez, and Marcelo V. Garcia

Subjects
Dynamic Matrix Control (DMC), IEC-61499, objective function, OPC-UA, optimization, predictive control, Chemical technology, TP1-1185
Abstract

This paper focuses on the implementation of a constrained Dynamic Matrix Control (DMC) approach within the level processes of the FESTO™ MPS-PA Compact Workstation plant in the context of the Industrial Internet of Things (IIoT) paradigm. The goal is to develop an industrial control application with decentralized logic that optimizes the operation of the plant while adhering to specific constraints. The implementation is carried out using the IEC-61499 standard and the OPC-UA protocol, enabling seamless communication between devices and systems. The authors utilize the 4diac-IDE and 4diac-FORTE as the development and runtime environments, respectively, to enable the execution of the control application on low-cost devices. The Beagle Bone Black (BBB) card is used for data acquisition and actuator control. Three types of constraints are considered: control increment (Δu(k)), output (ym(k)), and control (u(k)) constraints, to prevent unnecessary stress on the actuator and avoid damage to the plant. The QP algorithm is employed to optimize the objective function and address these constraints effectively. By integrating advanced control strategies into industrial processes in the IIoT paradigm and implementing them on low-cost devices, this paper demonstrates the feasibility and effectiveness of improving system performance, resource utilization, and overall productivity while considering system limitations and constraints.

Published
2023
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49. The root apoplastic pH as an integrator of plant signaling

Author

Francisco M. Gámez-Arjona, Clara Sánchez-Rodríguez, and Juan Carlos Montesinos

Subjects
pH, apoplast, root, signaling, plants, Plant culture, SB1-1110
Abstract

Plant nutrition, growth, and response to environmental stresses are pH-dependent processes that are regulated at the apoplastic and subcellular levels. The root apoplastic pH is especially sensitive to external cues and can also be modified by intracellular inputs, such as hormonal signaling. Optimal crosstalk of the mechanisms involved in the extent and span of the apoplast pH fluctuations promotes plant resilience to detrimental biotic and abiotic factors. The fact that variations in local pHs are a standard mechanism in different signaling pathways indicates that the pH itself can be the pivotal element to provide a physiological context to plant cell regions, allowing a proportional reaction to different situations. This review brings a collective vision of the causes that initiate root apoplastic pHs variations, their interaction, and how they influence root response outcomes.

Published
2022
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50. A Chromosome-Scale Genome Assembly for the Fusarium oxysporum Strain Fo5176 To Establish a Model Arabidopsis-Fungal Pathosystem

Author

Like Fokkens, Li Guo, Susanne Dora, Bo Wang, Kai Ye, Clara Sánchez-Rodríguez, and Daniel Croll

Subjects
fusarium oxysporum, arabidopsis thaliana, genome assembly, transposable elements, infection assays, comparative genomics, Genetics, QH426-470
Abstract

Plant pathogens cause widespread yield losses in agriculture. Understanding the drivers of plant-pathogen interactions requires decoding the molecular dialog leading to either resistance or disease. However, progress in deciphering pathogenicity genes has been severely hampered by suitable model systems and incomplete fungal genome assemblies. Here, we report a significant improvement of the assembly and annotation of the genome of the Fusarium oxysporum (Fo) strain Fo5176. Fo comprises a large number of serious plant pathogens on dozens of plant species with largely unresolved pathogenicity factors. The strain Fo5176 infects Arabidopsis thaliana and, hence, constitutes a highly promising model system. We use high-coverage Pacific Biosciences Sequel long-read and Hi-C sequencing data to assemble the genome into 19 chromosomes and a total genome size of 67.98 Mb. The genome has a N50 of 4 Mb and a 99.1% complete BUSCO score. Phylogenomic analyses based on single-copy orthologs clearly place the Fo5176 strain in the Fo f sp. conglutinans clade as expected. We generated RNAseq data from culture medium and plant infections to train gene predictions and identified ∼18,000 genes including ten effector genes known from other Fo clades. We show that Fo5176 is able to infect cabbage and Brussel sprouts of the Brassica oleracea, expanding the usefulness of the Fo5176 model pathosystem. Finally, we performed large-scale comparative genomics analyses comparing the Fo5176 to 103 additional Fo genomes to define core and accessory genomic regions. In conjunction with the molecular tool sets available for A. thaliana, the Fo5176 genome and annotation provides a crucial step toward the establishment of a highly promising pathosystem.

Published
2020
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