Cell fishing: A similarity based approach and machine learning strategy for multiple cell lines-compound sensitivity prediction.

The prediction of cell-lines sensitivity to a given set of compounds is a very important factor in the optimization of in-vitro assays. To date, the most common prediction strategies are based upon machine learning or other quantitative structure-activity relationships (QSAR) based approaches. In the present research, we propose and discuss a straightforward strategy not based on any learning modelling but exclusively relying upon the chemical similarity of a query compound to reference compounds with annotated activity against cell lines. We also compare the performance of the proposed method to machine learning predictions on the same problem. A curated database of compounds-cell lines associations derived from ChemBL version 22 was created for algorithm construction and cross-validation. Validation was done using 10-fold cross-validation and testing the models on new data obtained from ChemBL version 25. In terms of accuracy, both methods perform similarly with values around 0.65 across 750 cell lines in 10-fold cross-validation experiments. By combining both methods it is possible to achieve 66% of correct classification rate in more than 26000 newly reported interactions comprising 11000 new compounds. A Web Service implementing the described approaches (both similarity and machine learning based models) is freely available at: http://bioquimio.udla.edu.ec/cellfishing.

Hyphoderma paramacaronesicum sp. nov. (Meruliaceae, Polyporales, Basidiomycota), a cryptic lineage to H. macaronesicum.

This article re-evaluates the taxonomy of Hyphoderma macaronesicum based on various strategies, including the cohesion species recognition method through haplotype networks, multilocus genetic analyses using the genealogical concordance phylogenetic concept, as well as species tree reconstruction. The following loci were examined: the internal transcribed spacers of nuclear ribosomal DNA (ITS nrDNA), the intergenic spacers of nuclear ribosomal DNA (IGS nrDNA), two fragments of the protein-coding RNA polymerase II subunit 2 (RPB2), and two fragments of the translation elongation factor 1-α (EF1-α). Our results indicate that the name H. macaronesicum includes at least two separate species, one of which is newly described as Hyphoderma paramacaronesicum. The two species are readily distinguished based on the various loci analysed, namely ITS, IGS, RPB2 and EF1-α.

Unravelling the relationship between protein sequence and low-complexity regions entropies: Interactome implications.

Low-complexity regions are sub-sequences of biased composition in a protein sequence. The influence of these regions over protein evolution, specific functions and highly interactive capacities is well known. Although protein sequence entropy has been largely studied, its relationship with low-complexity regions and the subsequent effects on protein function remains unclear. In this work we propose a theoretical and empirical model integrating the sequence entropy with local complexity parameters. Our results indicate that the protein sequence entropy is related with the protein length, the entropies inside and outside the low-complexity regions as well as their number and average size. We found a small but significant increment in the sequence entropy of hubs proteins. In agreement with our theoretical model, this increment is highly dependent of the balance between the increment of protein length and average size of the low-complexity regions. Finally, our models and proteins analysis provide evidence supporting that modifications in the average size is more relevant in hubs proteins than changes in the number of low-complexity regions.

CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate immunological synapses.

In this study, we investigated the dynamics of the molecular interactions of tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the organization of the immune synapse (IS) and T cell activation. Using quantitative microscopy, including fluorescence recovery after photobleaching (FRAP), phasor fluorescence lifetime imaging microscopy-Föster resonance energy transfer (phasorFLIM-FRET), and total internal reflection fluorescence microscopy (TIRFM), we demonstrate that CD81 interacts with ICAM-1 and CD3 during conjugation between T cells and antigen-presenting cells (APCs). CD81 and ICAM-1 exhibit distinct mobilities in central and peripheral areas of early and late T cell-APC contacts. Moreover, CD81-ICAM-1 and CD81-CD3 dynamic interactions increase over the time course of IS formation, as these molecules redistribute throughout the contact area. Therefore, CD81 associations unexpectedly define novel sequential steps of IS maturation. Our results indicate that CD81 controls the temporal progression of the IS and the permanence of CD3 in the membrane contact area, contributing to sustained T cell receptor (TCR)-CD3-mediated signaling. Accordingly, we find that CD81 is required for proper T cell activation, regulating CD3ζ, ZAP-70, LAT, and extracellular signal-regulated kinase (ERK) phosphorylation; CD69 surface expression; and interleukin-2 (IL-2) secretion. Our data demonstrate the important role of CD81 in the molecular organization and dynamics of the IS architecture that sets the signaling threshold in T cell activation.

Epidemiology and molecular investigation of hepatitis C infection following holiday haemodialysis.

BACKGROUND: Hepatitis C virus infection (HCV) is not infrequent among haemodialysis patients. Most published reports suggest that patient-to-patient spread, either directly or indirectly, is the most common mode of transmission in renal units. AIM: To investigate the source of an outbreak, and the route of transmission, of acute HCV infection in two Scottish patients occurring within eight weeks of receiving haemodialysis in the same unit while on holiday in Majorca. METHODS: This was an international epidemiological and molecular investigation of HCV infection among a cohort of haemodialysis patients from nine countries. FINDINGS: No further HCV-positive infections were observed among residents and holidaymakers receiving haemodialysis at the unit in Majorca. Molecular investigations confirmed that a Spanish healthcare worker (HCW) was the source of infection for the two Scottish patients. The investigators were unable to determine the route of transmission. CONCLUSIONS: This outbreak is the first reported case of HCW-to-patient transmission of HCV in a renal unit, and the third reported case of transmission involving a HCW who had not performed invasive procedures. The issue of whether renal units are an exceptional case with regards to the risk of transmission associated with non-invasive procedures should be considered, in conjunction with the need to improve surveillance of blood-borne virus transmissions in renal units in the UK and abroad.

Application of desirability-based multi(bi)-objective optimization in the design of selective arylpiperazine derivates for the 5-HT1A serotonin receptor.

The multiobjective optimization technique based on the desirability estimation of several interrelated responses (MOOP-DESIRE) has been recently applied to quantitative structure-activity relationship (QSAR) studies. However, the advantage of applying this new methodology to the study of selectivity and affinity to competitive targets has been little explored. We used the MOOP-DESIRE methodology and a variation of this, to study the arylpiperazine derivates that could interact with 5-HT(1A) and 5-HT(2A), serotonin receptor subtypes with the objective of designing more selective molecules for the 5-HT(1A) receptor. We did show that the model results are in agreement with the available pharmacophore descriptions, guaranteeing an appropriate structural correlation and proving the methodology, as a useful tool for the important problem of selective drug design.

Description and culture of a new succulenticolous Didymium (Myxomycetes).

A new succulenticolous Myxomycete species, Didymium wildpretii, found on decaying remains of various species of cacti, is described from two arid zones of the world. This species was collected from central Mexico, at the southern limit of the Chihuahuan Desert, and from the Canary Islands (Spain). The new species has small, pale yellow sporocarps, 0.1-0.7 mm high, that are sessile or have short, orange-yellow, calcareous stalks and small, uniformly warted spores. The stability of the taxonomic characters of the species was confirmed with both moist chamber cultures and spore-to-spore culture on agar. Life cycle events are described from germination to sporulation. Myxomycete specimens were examined with scanning electron microscopy and light microscopy, and micrographs of relevant morphological details are included.

Difficidin and oxydifficidin: novel broad spectrum antibacterial antibiotics produced by Bacillus subtilis. I. Production, taxonomy and antibacterial activity.

Difficidin and oxydifficidin, two novel macrocyclic polyene lactone phosphate esters were discovered in fermentation broths of each of two strains of Bacillus subtilis: ATCC 39320 and ATCC 39374. Difficidin and oxydifficidin each showed a broad spectrum of activity against aerobic and anaerobic bacteria. Many of the susceptible aerobes and anaerobes were human pathogens resistant to one or more antibiotics. Difficidin and oxydifficidin when administered intraperitoneally protected mice against an otherwise lethal bacteremia caused by Klebsiella pneumoniae (ED50 in mg/kg of 1.31 and 15.6 respectively). Neither difficidin nor oxydifficidin were effective when administered via the subcutaneous route.