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Abstract The physical interactome of a protein can be altered upon perturbation, modulating cell physiology and contributing to disease. Identifying interactome differences of normal and disease states of proteins could help understand disease mechanisms, but current methods do not pinpoint structure-specific PPIs and interaction interfaces proteome-wide. We used limited proteolysis–mass spectrometry (LiP–MS) to screen for structure-specific PPIs by probing for protease susceptibility changes of proteins in cellular extracts upon treatment with specific structural states of a protein. We first demonstrated that LiP–MS detects well-characterized PPIs, including antibody–target protein interactions and interactions with membrane proteins, and that it pinpoints interfaces, including epitopes. We then applied the approach to study conformation-specific interactors of the Parkinson’s disease hallmark protein alpha-synuclein (aSyn). We identified known interactors of aSyn monomer and amyloid fibrils and provide a resource of novel putative conformation-specific aSyn interactors for validation in further studies. We also used our approach on GDP- and GTP-bound forms of two Rab GTPases, showing detection of differential candidate interactors of conformationally similar proteins. This approach is applicable to screen for structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound protein states.

Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modeling of interactions; and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across diverse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research.

Abstract Proteins are the key molecular machines that orchestrate all biological processes of the cell. Most proteins fold into three-dimensional shapes that are critical for their function. Studying the 3D shape of proteins can inform us of the mechanisms that underlie biological processes in living cells and can have practical applications in the study of disease mutations or the discovery of novel drug treatments. Here, we review the progress made in sequence-based prediction of protein structures with a focus on applications that go beyond the prediction of single monomer structures. This includes the application of deep learning methods for the prediction of structures of protein complexes, different conformations, the evolution of protein structures and the application of these methods to protein design. These developments create new opportunities for research that will have impact across many areas of biomedical research.

Objetivo. Determinar las pérdidas económicas producidas por el decomiso de hígados afectados y la prevalencia de Fasciola hepatica en bovinos sacrificados en las provincias de Holguín y Camagüey, Cuba. Materiales y métodos. Fueron utilizados los resultados del diagnóstico anatomopatológico realizado en los mataderos Felipe Fuentes y César Escalante durante el periodo comprendido entre enero de 2012 y diciembre de 2018. A partir de la cantidad de animales sacrificados y los afectados se calcularon las pérdidas que alcanzaron un valor de $80.312 USD (Holguín) y $32.7152 USD (Camagüey) para todo el período. Se realizaron análisis de comparación de proporciones para los animales afectados por F. hepatica y las pérdidas económicas por decomiso de hígados, mediante una prueba Chi-cuadrado para determinar la existencia o no de diferencias significativas entre las proporciones y un análisis de medias (ANOM) para determinar cuáles proporciones son significativamente distintas del promedio general. Resultados. Se observó que en 11 meses los animales afectados difirieron significativamente (p

Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types-phosphorylation and ubiquitination-in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis reveals a requirement for Aurora kinase activity in HIV-1 infection and identified putative substrates of a phosphatase that is degraded during infection. Finally, we demonstrate that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to defects in DNA repair.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6-all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.

Abstract Genome-wide association studies identified several disease-causing mutations in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the contribution of genetic variants to pathway disturbances and their cell type-specific variations, especially in glia, is poorly understood. We integrated ALS GWAS-linked gene networks with human astrocyte-specific multi-omics datasets to elucidate pathognomonic signatures. It predicts that KIF5A, a motor protein kinesin-1 heavy-chain isoform, previously detected only in neurons, can also potentiate disease pathways in astrocytes. Using postmortem tissue and super-resolution structured illumination microscopy in cell-based perturbation platforms, we provide evidence that KIF5A is present in astrocyte processes and its deficiency disrupts structural integrity and mitochondrial transport. We show that this may underly cytoskeletal and trafficking changes in SOD1 ALS astrocytes characterised by low KIF5A levels, which can be rescued by c-Jun N-terminal Kinase-1 (JNK1), a kinesin transport regulator. Altogether, our pipeline reveals a mechanism controlling astrocyte process integrity, a pre-requisite for synapse maintenance and suggests a targetable loss-of-function in ALS.

Abstract Understanding coding mutations is important for many applications in biology and medicine but the vast mutation space makes comprehensive experimental characterisation impossible. Current predictors are often computationally intensive and difficult to scale, including recent deep learning models. We introduce Sequence UNET, a highly scalable deep learning architecture that classifies and predicts variant frequency from sequence alone using multi-scale representations from a fully convolutional compression/expansion architecture. It achieves comparable pathogenicity prediction to recent methods. We demonstrate scalability by analysing 8.3B variants in 904,134 proteins detected through large-scale proteomics. Sequence UNET runs on modest hardware with a simple Python package.

Resumen: Introducción y objetivos: Analizar la evolución reciente del perfil de riesgo, la mortalidad y la actividad asistencial de la cirugía coronaria en España. Métodos: Se analizaron todos los episodios con códigos de procedimiento de cirugía aislada de revascularización coronaria del conjunto mínimo básico de datos en 2001-2020. El periodo de estudio se dividió en 4 etapas: 2001-2005, 2006-2010, 2011-2015 y 2016-2020. Se analizaron los cambios del volumen de actividad y los factores relacionados con la mortalidad hospitalaria mediante análisis de tendencia lineal y modelos multivariables de regresión logística. Resultados: Se incluyeron 96.073 episodios de donde se realizó una cirugía coronaria aislada. Se observó una reducción del volumen anual de cirugías de 6.134 en 2001 a 3.421 en 2020, y un aumento de la ratio intervencionismo coronario/cirugía de 2,4 a 8. Entre el primero y el último periodo, se produjo un aumento de casi todas las comorbilidades con un incremento del índice de Charlson medio de 2,99 a 3,68 (p

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.

Protein phosphorylation is a key post-translational modification regulating protein function in almost all cellular processes. Although tens of thousands of phosphorylation sites have been identified in human cells, approaches to determine the functional importance of each phosphosite are lacking. Here, we manually curated 112 datasets of phospho-enriched proteins, generated from 104 different human cell types or tissues. We re-analyzed the 6,801 proteomics experiments that passed our quality control criteria, creating a reference phosphoproteome containing 119,809 human phosphosites. To prioritize functional sites, we used machine learning to identify 59 features indicative of proteomic, structural, regulatory or evolutionary relevance and integrate them into a single functional score. Our approach identifies regulatory phosphosites across different molecular mechanisms, processes and diseases, and reveals genetic susceptibilities at a genomic scale. Several regulatory phosphosites were experimentally validated, including identifying a role in neuronal differentiation for phosphosites in SMARCC2, a member of the SWI/SNF chromatin-remodeling complex.

This paper presents a literature survey of more than twenty years on AC/DC multilevel converters with reduced switch count, in which some power switches can be removed letting only diodes. This simplification reduces the number of gate drivers, cost and complexity of the system. In this work, the considered topologies are derived from the conventional multilevel configurations on literature: Neutral Point Clamped, Cascaded H-Bridge, Flying Capacitor, Modular Multilevel Converter and T-Type. This article is divided in five sections, each one with papers with topologies derived from the five multilevel configurations previously mentioned. In each section, there are up to a maximum of four subsections, considering the main focus of each paper and contribution: derived and hybrid topologies, control techniques, analysis and hardware and design. At the end of each section, a summary table concerning the referenced papers is shown containing comparison information among the presented references in terms of: number of components per phase of the studied converter, applied modulation technique, applied control technique, suggested application given by the authors, converter’s output power considered and the respective efficiency considering this point of operation. With this extensive bibliography work, this paper serves as a very good reference to researchers interested in the topic to initiate their work or to update their studies. Also, the applications suggested by the authors give a direction of which topologies fit best different applications.

Abstract Genetic alterations in cancer cells trigger oncogenic transformation, a process largely mediated by the dysregulation of kinase and transcription factor (TF) activities. While the mutational profiles of thousands of tumours have been extensively characterised, the measurements of protein activities have been technically limited until recently. We compiled public data of matched genomics and (phospho)proteomics measurements for 1,110 tumours and 77 cell lines that we used to estimate activity changes in 218 kinases and 292 TFs. Co‐regulation of kinase and TF activities reflects previously known regulatory relationships and allows us to dissect genetic drivers of signalling changes in cancer. We find that loss‐of‐function mutations are not often associated with the dysregulation of downstream targets, suggesting frequent compensatory mechanisms. Finally, we identified the activities most differentially regulated in cancer subtypes and showed how these can be linked to differences in patient survival. Our results provide broad insights into the dysregulation of protein activities in cancer and their contribution to disease severity.

Antecedentes: La fasciolosis es una enfermedad parasitaria que afecta no solo al ganado bovino y ovino sino también al humano, presenta distribución global, con mayor incidencia en zonas tropicales y subtropicales. Objetivo. realizar una revisión acerca de Fasciola hepatica, valoración del contexto nacional y mundial, ciclo biológico, patogenia, signos clínicos, control y prevención, epidemiología, efecto zoonótico, estacionalidad y efectos económicos que genera su presentación en las explotaciones ganaderas. Desarrollo: Las evidencias obtenidas como resultado del proceso investigativo han determinado la inclusión del parásito dentro del grupo de las enfermedades emergentes. Fasciola sp. además de ser una de las principales causas de decomiso del hígado en los mataderos, implica otros daños asociados a la infección: disminución de la producción de carne, leche o lana y peso corporal, infertilidad, disminución del crecimiento, retraso reproductivo, abortos y pérdida de resistencia a otras enfermedades. Los costos aumentan, debido a los tratamientos antihelmínticos, así como a infecciones bacterianas secundarias frecuentes, que pueden llevar a la muerte de animales. Conclusión: Las pérdidas económicas que ocurren por el decomiso de hígados afectados por F. hepatica son relevantes y dependen de la interacción entre los aspectos fisiopatológicos de la enfermedad y los ambientales (factores climatológicos y geográficos) que determinan la presencia de hospederos intermediarios y el parásito en el ambiente. Palabras clave: decomisos, F. hepatica, infestación, trematodo (Fuente: DeCS)

Aim. The COVID-19 pandemic devastated healthcare around the world. Data about the COVID-19 outcomes among young people are still scarce. We aim to identify factors associated with the composite outcome among children and adolescents hospitalized due to COVID-19. Methods. We performed a search in the database of a large Brazilian private healthcare system. Insured people aged 21 years or younger who were hospitalized due to COVID-19 from Feb/28th/2020 to Nov/1st/2021 were included. The primary endpoint was the composite outcome consisting of ICU admission, need for invasive mechanical ventilation, or death. Results. We evaluated 199 patients who had an index hospitalization due to COVID-19. The median monthly rate of index hospitalization was 2.7 (interquartile range [IQR], 1.6-3.9) per 100,000 clients aged 21 years or less. The median age of the patients was 4.5 years (IQR, 1.4-14.1). At the index hospitalization, the composite outcome rate was 26.6%. The composite outcome was associated with all the previous coexisting morbidities evaluated. The median follow-up was 249.0 days (IQR, 152.0-438.5). There were 27 readmissions (16 patients) within 30 days after the discharge. Conclusions. In conclusion, hospitalized children and adolescents had a composite outcome rate of 26.6% at the index hospitalization. Having previous chronic morbidity was associated with the composite.

Resumen: La enfermedad coronaria en candidatos a implante de prótesis aórtica transcatéter es frecuente. El abordaje híbrido que combina el implante de una prótesis transcatéter por vía transapical y la revascularización miocárdica quirúrgica mínimamente invasiva es una opción segura y eficaz en pacientes con enfermedad vascular periférica o estenosis en la arteria coronaria descendente anterior no apta para intervención percutánea. Reportamos nuestra experiencia en 2 casos. Abstract: Coronary artery disease in transcatheter aortic valve implantation candidates is prevalent. Hybrid approach combining transapical valve implantation and minimally invasive direct coronary artery bypass is a safe and effective option in patients with peripheral vascular disease and/or stenosis in left anterior coronary artery not suitable for percutaneous intervention. We report our experience in 2 cases.

Abstract Amino acids fulfil a diverse range of roles in proteins, each utilising its chemical properties in different ways in different contexts to create required functions. For example, cysteines form disulphide or hydrogen bonds in different circumstances and charged amino acids do not always make use of their charge. The repertoire of amino acid functions and the frequency at which they occur in proteins remains understudied. Measuring large numbers of mutational consequences, which can elucidate the role an amino acid plays, was prohibitively time‐consuming until recent developments in deep mutational scanning. In this study, we gathered data from 28 deep mutational scanning studies, covering 6,291 positions in 30 proteins, and used the consequences of mutation at each position to define a mutational landscape. We demonstrated rich relationships between this landscape and biophysical or evolutionary properties. Finally, we identified 100 functional amino acid subtypes with a data‐driven clustering analysis and studied their features, including their frequencies and chemical properties such as tolerating polarity, hydrophobicity or being intolerant of charge or specific amino acids. The mutational landscape and amino acid subtypes provide a foundational catalogue of amino acid functional diversity, which will be refined as the number of studied protein positions increases.

Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS‐CoV‐2 hijacks host cellular machineries on a system‐wide scale so that potential host‐directed therapies can be developed. In situ proteome‐wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS‐CoV‐2 handling. We discovered pronounced temporal alterations in host protein thermostability during infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during infection suppressed SARS‐CoV‐2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS‐CoV‐2 infection.

Abstract Multi‐omics datasets can provide molecular insights beyond the sum of individual omics. Various tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi‐Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolomics datasets. COSMOS combines extensive prior knowledge of signaling, metabolic, and gene regulatory networks with computational methods to estimate activities of transcription factors and kinases as well as network‐level causal reasoning. COSMOS provides mechanistic hypotheses for experimental observations across multi‐omics datasets. We applied COSMOS to a dataset comprising transcriptomics, phosphoproteomics, and metabolomics data from healthy and cancerous tissue from eleven clear cell renal cell carcinoma (ccRCC) patients. COSMOS was able to capture relevant crosstalks within and between multiple omics layers, such as known ccRCC drug targets. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi‐omics studies.

Abstract Since the start of 2020, the world has been upended by the pandemic caused by the severe acute respiratory coronavirus type 2 (SARS‐CoV‐2), the causative agent of coronavirus disease 2019 (COVID‐19). It has not only led to a tragic loss of life and terrible economic costs but has also been met with an unprecedented response of the scientific and medical communities. In an effort to better understand this viral infection, scientists around the world generated the largest surge in research in documented history for any topic (Lever & Altman, 2021). A part of this work has included the need to better understand the impact of the virus on human proteins—the key machinery of the cell—and human physiology. In their recent study, Geyer and colleagues (Geyer et al, 2021) analyzed a total of 720 proteomes from longitudinal serum samples of 31 hospitalized COVID‐19 patients and control individuals with COVID‐19‐like symptoms but not infected with SARS‐CoV‐2, providing a comprehensive characterization of the plasma proteome changes along the time course of infection.

Antecedentes: La fasciolosis es una enfermedad parasitaria que afecta no solo al ganado bovino y ovino sino también al humano, presenta distribución global, con mayor incidencia en zonas tropicales y subtropicales. Objetivo. realizar una revisión acerca de Fasciola hepatica, valoración del contexto nacional y mundial, ciclo biológico, patogenia, signos clínicos, control y prevención, epidemiología, efecto zoonótico, estacionalidad y efectos económicos que genera su presentación en las explotaciones ganaderas. Desarrollo: Las evidencias obtenidas como resultado del proceso investigativo han determinado la inclusión del parásito dentro del grupo de las enfermedades emergentes. Fasciola sp. además de ser una de las principales causas de decomiso del hígado en los mataderos, implica otros daños asociados a la infección: disminución de la producción de carne, leche o lana y peso corporal, infertilidad, disminución del crecimiento, retraso reproductivo, abortos y pérdida de resistencia a otras enfermedades. Los costos aumentan, debido a los tratamientos antihelmínticos, así como a infecciones bacterianas secundarias frecuentes, que pueden llevar a la muerte de animales. Conclusión: Las pérdidas económicas que ocurren por el decomiso de hígados afectados por F. hepatica son relevantes y dependen de la interacción entre los aspectos fisiopatológicos de la enfermedad y los ambientales (factores climatológicos y geográficos) que determinan la presencia de hospederos intermediarios y el parásito en el ambiente.

Resumen: Introducción y objetivos: La revascularización coronaria de la arteria descendente anterior (DA) mediante derivación aortocoronaria mínimamente invasiva (MIDCAB) mantiene los beneficios del uso de la arteria mamaria interna izquierda y evita las complicaciones asociadas a la esternotomía media y a la circulación extracorpórea. El objetivo es presentar nuestra experiencia inicial en el MIDCAB. Material y método: Se incluyeron todos los pacientes intervenidos mediante MIDCAB de marzo 2019 a junio del 2020. En todos los pacientes se realizó un puente coronario de arteria mamaria interna izquierda a la descendente anterior mediante minitoracotomía anterolateral izquierda sin circulación extracorpórea. Resultados: Se intervinieron 22 pacientes. La mediana de edad era de 70 años (IQR 63-77) y el 90,9% (n = 20) eran varones. En dos pacientes con estenosis aórtica severa se realizó simultáneamente implante de una prótesis aórtica transcatéter por vía transapical y en ocho (36,4%) pacientes se realizó un procedimiento híbrido con revascularización percutánea al resto de lesiones. No hubo mortalidad hospitalaria, infarto agudo de miocardio, accidente cerebrovascular, ni fracaso renal agudo postoperatorio. La mediana de estancia hospitalaria fue de cuatro días (IQR 3-5). Conclusiones: El MIDCAB es una técnica segura y eficaz para la revascularización coronaria en el territorio de la descendente anterior que combina las ventajas de un abordaje mínimamente invasivo sin circulación extracorpórea y el uso de la arteria mamaria interna izquierda para la realización de un puente coronario. Summary: Introduction and objectives: Coronary revascularization of the anterior descending artery (DA) using MIDCAB (Minimally Invasive Direct Coronary Artery Bypass) maintains the benefits of the use of the left internal mammary artery (AMII) and avoids the complications associated with middle sternotomy and extracorporeal circulation. The objective is to present our initial experience at MIDCAB. Material and method: All patients who underwent MIDCAB from March 2019 to June 2020 were included. In all patients, a left internal mammary artery bypass was performed to the anterior descending artery using a left anterolateral minithoracotomy without extracorporeal circulation. Results: 22 patients. The median age was 70 years (IQR 63-77) and 90.9% (n = 20) were male. Transapical aortic valve implantation was performed simultaneously in two patients with severe aortic stenosis and in 8 (36.4%) patients a hybrid procedure with percutaneous coronay intervention was performed for the rest of the lesions. There were no hospital mortality, miocardial infarction, stroke, or postoperative acute renal failure. The median hospital stay was 4 days (IQR 3-5). Conclusions: MIDCAB is a safe and effective technique for coronary revascularization in the left anterior descending coronary artery that combines the advantages of a minimally invasive approach without extracorporeal circulation and the use of the left internal mammary artery bypass.

The main purpose of the study was to evaluate of effectiveness of the halophyte plants on saline soils and use as a salt-tolerant plants. The experimental studies carried out on the halophyte plants (Tetragonia tetragonioides and Portulaca oleracea) and the salt-sensitive crop (Lactuca sativa, L) in the greenhouse. Two experimental studies were conducted on the effects of salt on germination, total yield and mineral composition of the halophyte plants and salt-sensitive crop. Three salinity treatments (saline water solution with NaCl: T1 - 5 dS m−1; T2 - 9.8 dS m−1; and T3 - 20 dS m−1) and a control treatment (T0 - 0.6 dS m−1) were used for the experimental study. The both halophyte plants showed the potential salt (ions) removing species with high yields when grown on saline soils. The results showed that the above halophytes varieties contributed to improved quality and yield of the salt-sensitive crop. Thus, this method has proven to be one of the important solutions in preventing and managing salinity and ensuring the sustainability of agricultural systems. Analysis of the obtained results showed that halophyte plants could be used to improve the management and stability of saline soils and grow them as food crops.

Abstract Loss‐of‐function (LoF) mutations associated with disease do not manifest equally in different individuals. The impact of the genetic background on the consequences of LoF mutations remains poorly characterized. Here, we systematically assessed the changes in gene deletion phenotypes for 3,786 gene knockouts in four Saccharomyces cerevisiae strains and 38 conditions. We observed 18.5% of deletion phenotypes changing between pairs of strains on average with a small fraction conserved in all four strains. Conditions causing higher wild‐type growth differences and the deletion of pleiotropic genes showed above‐average changes in phenotypes. In addition, we performed a genome‐wide association study (GWAS) for growth under the same conditions for a panel of 925 yeast isolates. Gene–condition associations derived from GWAS were not enriched for genes with deletion phenotypes under the same conditions. However, cases where the results were congruent indicate the most likely mechanism underlying the GWAS signal. Overall, these results show a high degree of genetic background dependencies for LoF phenotypes.

© 2015 The Authors.Abstract Genetic interaction screens have been applied with great success in several organisms to study gene function and the genetic architecture of the cell. However, most studies have been performed under optimal growth conditions eve

© 2015 Johnson et al.The African clawed frog Xenopus laevis is an important model organism for studies in developmental and cell biology, including cell-signaling. However, our knowledge of X. laevis protein post-translational modifications remains scarce.