Ground temperatures, landforms and processes in an Atlantic mountain. Cantabrian Mountains (Northern Spain)

This research was supported by the Formación de Profesorado Universitario FPU13/05837 (Ministerio de Educación Cultura y Deporte) program, by the OAPN 053/2010 (Organismo Autónomo Parques Nacionales, MAGRAMA) project, by the I + D + I CGL2015-68144-R (Ministerio de Economia y Competitividad) project, by the Leverhulme Trust International Network Grant IN-2012-140 and the Royal Geographical Society Dudley Stamp Memorial Award.Peer reviewedPostprin

Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division

Proliferation of mammalian cells requires the coordinated function of many proteins to accurately divide a cell into two daughter cells. Several RNAi screens have identified previously uncharacterised genes that are implicated in mammalian cell division. The molecular function for these genes needs to be investigated to place them into pathways. Phenotypic profiling is a useful method to assign putative functions to uncharacterised genes. Here, we show that the analysis of protein localisation is useful to refine a phenotypic profile. We show the utility of this approach by defining a function of the previously uncharacterised gene C13orf3 during cell division. C13orf3 localises to centrosomes, the mitotic spindle, kinetochores, spindle midzone, and the cleavage furrow during cell division and is specifically phosphorylated during mitosis. Furthermore, C13orf3 is required for centrosome integrity and anaphase onset. Depletion by RNAi leads to mitotic arrest in metaphase with an activation of the spindle assembly checkpoint and loss of sister chromatid cohesion. Proteomic analyses identify C13orf3 (Ska3) as a new component of the Ska complex and show a direct interaction with a regulatory subunit of the protein phosphatase PP2A. All together, these data identify C13orf3 as an important factor for metaphase to anaphase progression and highlight the potential of combined RNAi screening and protein localisation analyses

A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

We have identified a novel gene in a genome-wide, double-strand break DNA repair RNAi screen and show that is involved in the neurological disease hereditary spastic paraplegia

3D Profile-Based Approach to Proteome-Wide Discovery of Novel Human Chemokines

Chemokines are small secreted proteins with important roles in immune responses. They consist of a conserved three-dimensional (3D) structure, so-called IL8-like chemokine fold, which is supported by disulfide bridges characteristic of this protein family. Sequence- and profile-based computational methods have been proficient in discovering novel chemokines by making use of their sequence-conserved cysteine patterns. However, it has been recently shown that some chemokines escaped annotation by these methods due to low sequence similarity to known chemokines and to different arrangement of cysteines in sequence and in 3D. Innovative methods overcoming the limitations of current techniques may allow the discovery of new remote homologs in the still functionally uncharacterized fraction of the human genome. We report a novel computational approach for proteome-wide identification of remote homologs of the chemokine family that uses fold recognition techniques in combination with a scaffold-based automatic mapping of disulfide bonds to define a 3D profile of the chemokine protein family. By applying our methodology to all currently uncharacterized human protein sequences, we have discovered two novel proteins that, without having significant sequence similarity to known chemokines or characteristic cysteine patterns, show strong structural resemblance to known anti-HIV chemokines. Detailed computational analysis and experimental structural investigations based on mass spectrometry and circular dichroism support our structural predictions and highlight several other chemokine-like features. The results obtained support their functional annotation as putative novel chemokines and encourage further experimental characterization. The identification of remote homologs of human chemokines may provide new insights into the molecular mechanisms causing pathologies such as cancer or AIDS, and may contribute to the development of novel treatments. Besides, the genome-wide applicability of our methodology based on 3D protein family profiles may open up new possibilities for improving and accelerating protein function annotation processes

Genomic expression profiling of human inflammatory cardiomyopathy (DCMi) suggests novel therapeutic targets

The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. As targeting of etiology-related pathogenic pathways may be more efficient than current standard heart failure treatment, we obtained the genomic expression profile of a DCM subtype characterized by cardiac inflammation to identify possible new therapeutic targets in humans. In this inflammatory cardiomyopathy (DCMi), a distinctive cardiac expression pattern not described in any previous study of cardiac disorders was observed. Two significantly altered gene networks of particular interest and possible interdependence centered around the cysteine-rich angiogenic inducer 61 (CYR61) and adiponectin (APN) gene. CYR61 overexpression, as in human DCMi hearts in situ, was similarly induced by inflammatory cytokines in vascular endothelial cells in vitro. APN was strongly downregulated in DCMi hearts and completely abolished cytokine-dependent CYR61 induction in vitro. Dysbalance between the CYR61 and APN networks may play a pathogenic role in DCMi and contain novel therapeutic targets. Multiple immune cell-associated genes were also deregulated (e.g., chemokine ligand 14, interleukin-17D, nuclear factors of activated T cells). In contrast to previous investigations in patients with advanced or end-stage DCM where etiology-related pathomechanisms are overwhelmed by unspecific processes, the deregulations detected in this study occurred at a far less severe and most probably fully reversible disease stage. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00109-006-0122-9 and is accessible for authorized users

PhenoFam-gene set enrichment analysis through protein structural information

<p>Abstract</p> <p>Background</p> <p>With the current technological advances in high-throughput biology, the necessity to develop tools that help to analyse the massive amount of data being generated is evident. A powerful method of inspecting large-scale data sets is gene set enrichment analysis (GSEA) and investigation of protein structural features can guide determining the function of individual genes. However, a convenient tool that combines these two features to aid in high-throughput data analysis has not been developed yet. In order to fill this niche, we developed the user-friendly, web-based application, PhenoFam.</p> <p>Results</p> <p>PhenoFam performs gene set enrichment analysis by employing structural and functional information on families of protein domains as annotation terms. Our tool is designed to analyse complete sets of results from quantitative high-throughput studies (gene expression microarrays, functional RNAi screens, <it>etc</it>.) without prior pre-filtering or hits-selection steps. PhenoFam utilizes Ensembl databases to link a list of user-provided identifiers with protein features from the InterPro database, and assesses whether results associated with individual domains differ significantly from the overall population. To demonstrate the utility of PhenoFam we analysed a genome-wide RNA interference screen and discovered a novel function of plexins containing the cytoplasmic RasGAP domain. Furthermore, a PhenoFam analysis of breast cancer gene expression profiles revealed a link between breast carcinoma and altered expression of PX domain containing proteins.</p> <p>Conclusions</p> <p>PhenoFam provides a user-friendly, easily accessible web interface to perform GSEA based on high-throughput data sets and structural-functional protein information, and therefore aids in functional annotation of genes.</p

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

International audienceno abstrac

Sensory Perception of Food and Insulin-Like Signals Influence Seizure Susceptibility

Food deprivation is known to affect physiology and behavior. Changes that occur could be the result of the organism's monitoring of internal and external nutrient availability. In C. elegans, male mating is dependent on food availability; food-deprived males mate with lower efficiency compared to their well-fed counterparts, suggesting that the mating circuit is repressed in low-food environments. This behavioral response could be mediated by sensory neurons exposed to the environment or by internal metabolic cues. We demonstrated that food-deprivation negatively regulates sex-muscle excitability through the activity of chemosensory neurons and insulin-like signaling. Specifically, we found that the repressive effects of food deprivation on the mating circuit can be partially blocked by placing males on inedible food, E. coli that can be sensed but not eaten. We determined that the olfactory AWC neurons actively suppress sex-muscle excitability in response to food deprivation. In addition, we demonstrated that loss of insulin-like receptor (DAF-2) signaling in the sex muscles blocks the ability of food deprivation to suppress the mating circuit. During low-food conditions, we propose that increased activity by specific olfactory neurons (AWCs) leads to the release of neuroendocrine signals, including insulin-like ligands. Insulin-like receptor signaling in the sex muscles then reduces cell excitability via activation of downstream molecules, including PLC-γ and CaMKII