Genetic variations and diseases in UniProtKB/Swiss-Prot: the ins and outs of expert manual curation.

During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease.

Experts bodies, experts minds: How physical and mental training shape the brain.

Skill learning is the improvement in perceptual, cognitive, or motor performance following practice. Expert performance levels can be achieved with well-organized knowledge, using sophisticated and specific mental representations and cognitive processing, applying automatic sequences quickly and efficiently, being able to deal with large amounts of information, and many other challenging task demands and situations that otherwise paralyze the performance of novices. The neural reorganizations that occur with expertise reflect the optimization of the neurocognitive resources to deal with the complex computational load needed to achieve peak performance.

[ROS and NADPH oxidase: key regulators of tumor vascularisation].

Oxidative stress is the result of an imbalance between the production of reactive oxygen species (ROS) and antioxidant mechanisms. It is characterized by damage of all cellular components, DNA, proteins, lipids. ROS are nevertheless important for the physiology of an organism, as they are involved in the innate immune defense and several intracellular signaling pathways.

Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: a new role for lymphatic endothelial cells.

Until recently, the known roles of lymphatic endothelial cells (LECs) in immune modulation were limited to directing immune cell trafficking and passively transporting peripheral Ags to lymph nodes. Recent studies demonstrated that LECs can directly suppress dendritic cell maturation and present peripheral tissue and tumor Ags for autoreactive T cell deletion. We asked whether LECs play a constitutive role in T cell deletion under homeostatic conditions.

[Prostate-rectum spacers: optimization of prostate cancer irradiation].

In the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity. The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease. Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7-to-20 mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months.

Motifs tree: a new method for predicting post-translational modifications.

Motivation: Post-translational modifications (PTMs) are important steps in the maturation of proteins. Several models exist to predict specific PTMs, from manually detected patterns to machine learning methods. On one hand, the manual detection of patterns does not provide the most efficient classifiers and requires an important workload, and on the other hand, models built by machine learning methods are hard to interpret and do not increase biological knowledge.

Matricellular protein CCN1/CYR61: a new player in inflammation and leukocyte trafficking.

Cystein-rich protein 61 (CYR61/CCN1) is a component of the extracellular matrix, which is produced and secreted by several cell types including endothelial cells, fibroblasts and smooth muscle cells. CCN1 has been implicated in leukocyte migration and the inflammatory process, but it is also involved in cardiovascular development and carcinogenesis. It exerts its functions through binding to multiple integrins present in many different cell types.

Intracellular killing of bacteria: is Dictyostelium a model macrophage or an alien?

Predation of bacteria by phagocytic cells was first developed during evolution by environmental amoebae. Many of the core mechanisms used by amoebae to sense, ingest and kill bacteria have also been conserved in specialized phagocytic cells in mammalian organisms. Here we focus on recent results revealing how Dictyostelium discoideum senses and kills non-pathogenic bacteria.

Expert curation in UniProtKB: a case study on dealing with conflicting and erroneous data.

UniProtKB/Swiss-Prot provides expert curation with information extracted from literature and curator-evaluated computational analysis. As knowledgebases continue to play an increasingly important role in scientific research, a number of studies have evaluated their accuracy and revealed various errors. While some are curation errors, others are the result of incorrect information published in the scientific literature.

Role of PKD2 in rheotaxis in Dictyostelium.

The sensing of mechanical forces modulates several cellular responses as adhesion, migration and differentiation. Transient elevations of calcium concentration play a key role in the activation of cells following mechanical stress, but it is still unclear how eukaryotic cells convert a mechanical signal into an ion flux. In this study, we used the model organism Dictyostelium discoideum to assess systematically the role of individual calcium channels in mechanosensing.

Voltage-Gated Proton Channels as Novel Drug Targets: From NADPH Oxidase Regulation to Sperm Biology.

Significance: Voltage-gated proton channels are increasingly implicated in cellular proton homeostasis. Proton currents were originally identified in snail neurons less than 40 years ago, and subsequently shown to play an important auxiliary role in the functioning of reactive oxygen species (ROS)-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Molecular identification of voltage-gated proton channels was achieved less than 10 years ago.

TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock or microbial sepsis have so far mostly relied on the administration of TREM-1 fusion proteins or peptides representing part of the extracellular domain of TREM-1.

The EBI RDF platform: linked open data for the life sciences.

Resource description framework (RDF) is an emerging technology for describing, publishing and linking life science data. As a major provider of bioinformatics data and services, the European Bioinformatics Institute (EBI) is committed to making data readily accessible to the community in ways that meet existing demand. The EBI RDF platform has been developed to meet an increasing demand to coordinate RDF activities across the institute and provides a new entry point to querying and exploring integrated resources available at the EBI.

Management guidelines of eosinophilic esophagitis in childhood.

Objectives: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor-responsive esophageal eosinophilia.

Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output.

Thymic epithelial cells (TEC) are heterogeneous stromal cells that generate microenvironments required for the formation of T cells within the thymus. Defects in TEC lead to immunodeficiency or autoimmunity. Here we identify TEC as the major source of cysteine-rich protein 61 (CYR61), a matricellular protein implicated in cell proliferation and migration.

MiR-27 orchestrates the transcriptional regulation of brown adipogenesis.

Objective: Brown adipose tissue (BAT) produces heat using chemical energy of lipids and glucose, a function induced by cold exposure or diet. The brown adipogenesis is tightly controlled in a coordinated interplay between several transcriptional factors. It is not known what enables and coordinates this robust program of concerted cooperation between the transcriptional factors and co-regulators necessary for the brown adipogenesis.

[Factors associated with HPV immunization for 13-14-year-old girls in the Geneva district, Switzerland].

Background: School vaccination programs against human papilloma virus (HPV) have been implemented in most Western countries. Only a few studies have investigated socio-economic factors related to school-based vaccination.

Method: A cross-sectional study was conducted using the vaccination cards of 1158 randomized girls aged 13 to 14 years enrolled in the public schools of the canton of Geneva.

New insights on NOX enzymes in the central nervous system.

Significance: There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redox-sensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease.

Recent Advances: NOX enzymes are not only restricted to microglia (i.

A practical guide for the diagnosis of primary enteric nervous system disorders.

Objective: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders.

Two distinct sensing pathways allow recognition of Klebsiella pneumoniae by Dictyostelium amoebae.

Recognition of bacteria by metazoans is mediated by receptors that recognize different types of microorganisms and elicit specific cellular responses. The soil amoebae Dictyostelium discoideum feeds upon a variable mixture of environmental bacteria, and it is expected to recognize and adapt to various food sources. To date, however, no bacteria-sensing mechanisms have been described.

Use of in vivo biotinylated GST fusion proteins to select recombinant antibodies.

Over the last 20 years, continuous advances in the field of molecular biology have led to the development of new strategies to discover and produce monoclonal antibodies, notably by phage display.Here we describe a simple procedure for antibody selection that reduces considerably the undesired selection of non-specific antibodies, based on the use of biotinylated GST proteins fused to a target antigenic sequence. This procedure was tested on a collection of 7 different targets and resulted in the selection of a high percentage (71%) of antibodies specific for each target.

[Renovascular prognosis of preeclampsia on the mother and the child].

Preeclampsia is a pregnancy-related disease that affects 2 to 8% of pregnancy worldwide. It is now a well-established risk factor for cardiovascular and renal diseases. Preeclampsia is a well-recognized risk factor for future cardiovascular, renal and neurological disorders for the mother.

A fast Peptide Match service for UniProt Knowledgebase.

Summary: We have developed a new web application for peptide matching using Apache Lucene-based search engine. The Peptide Match service is designed to quickly retrieve all occurrences of a given query peptide from UniProt Knowledgebase (UniProtKB) with isoforms. The matched proteins are shown in summary tables with rich annotations, including matched sequence region(s) and links to corresponding proteins in a number of proteomic/peptide spectral databases.

Effects of step duration in incremental ramp protocols on peak power and maximal oxygen consumption.

Purpose: Morton (J Sport Sci 29:307-309, 2011) proposed a model of the peak power attained in ramp protocol ([Formula: see text]) that included critical power (CP) and anaerobic capacity as constants, and mean ramp slope (S) as variable. Our hypothesis is that [Formula: see text] depends only on S, so that Morton's model should be applicable in all types of ramps. The aim of this study was to test this hypothesis by validating Morton's model using stepwise ramp tests with invariant step increment and increasing step duration.