The Regional Student Group Program of the ISCB Student Council: Stories from the Road

The International Society for Computational Biology (ISCB) Student Council was launched in 2004 to facilitate interaction between young scientists in the fields of bioinformatics and computational biology. Since then, the Student Council has successfully run events and programs to promote the development of the next generation of computational biologists. However, in its early years, the Student Council faced a major challenge, in that students from different geographical regions had different needs; no single activity or event could address the needs of all students. To overcome this challenge, the Student Council created the Regional Student Group (RSG) program. The program consists of locally organised and run student groups that address the specific needs of students in their region. These groups usually encompass a given country, and, via affiliation with the international Student Council, are provided with financial support, organisational support, and the ability to share information with other RSGs. In the last five years, RSGs have been created all over the world and organised activities that have helped develop dynamic bioinformatics student communities. In this article series, we present common themes emerging from RSG initiatives, explain their goals, and highlight the challenges and rewards through specific examples. This article, the first in the series, introduces the Student Council and provides a high-level overview of RSG activities. Our hope is that the article series will be a valuable source of information and inspiration for initiating similar activities in other regions and scientific communities.     

Pancreatic ductal adenocarcinomas from Mexican patients present a distinct genomic mutational pattern

Molecular Biology Reports - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in humans, with less than 5% 5-year survival rate. PDAC is characterized by a small number of...     

Colonization of Madagascar periwinkle (Catharanthus roseus), by endophytes encoding gfp marker

This study reports the introduction of gfp marker in two endophytic bacterial strains (Pantoea agglomerans C33.1, isolated from cocoa, and Enterobacter cloacae PR2/7, isolated from citrus) to monitor the colonization in Madagascar perinwinkle (Catharanthus roseus). Stability of the plasmid encoding gfp was confirmed in vitro for at least 72 h of bacterial growth and after the colonization of tissues, under non-selective conditions. The colonization was observed using fluorescence microscopy and enumeration of culturable endophytes in inoculated perinwinkle plants that grew for 10 and 20 days. Gfp-expressing strains were re-isolated from the inner tissues of surface-sterilized roots and stems of inoculated plants, and the survival of the P. agglomerans C33:1gfp in plants 20 days after inoculation, even in the absence of selective pressure, suggests that is good colonizer. These results indicated that both gfp-tagged strains, especially P. agglomerans C33.1, may be useful tools to deliver enzymes or other proteins in plant.     

Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation

Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ?K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ?K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (?K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ?K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ?K107 or ?K226.     

Effects of surfactin on membrane models displaying lipid phase separation

Surfactin, a bacterial amphiphilic lipopeptide is attracting more and more attention in view of its bioactive properties which are in relation with its ability to interact with lipids of biological membranes. In this work, we investigated the effect of surfactin on membrane structure using model of membranes, vesicles as well as supported bilayers, presenting coexistence of fluid-disordered (DOPC) and gel (DPPC) phases. A range of complementary methods was used including AFM, ellipsometry, dynamic light scattering, fluorescence measurements of Laurdan, DPH, calcein release, and octadecylrhodamine B dequenching. Our findings demonstrated that surfactin concentration is critical for its effect on the membrane. The results suggest that the presence of rigid domains can play an essential role in the first step of surfactin insertion and that surfactin interacts both with the membrane polar heads and the acyl chain region. A mechanism for the surfactin lipid membrane interaction, consisting of three sequential structural and morphological changes, is proposed. At concentrations below the CMC, surfactin inserted at the boundary between gel and fluid lipid domains, inhibited phase separation and stiffened the bilayer without global morphological change of liposomes. At concentrations close to CMC, surfactin solubilized the fluid phospholipid phase and increased order in the remainder of the lipid bilayer. At higher surfactin concentrations, both the fluid and the rigid bilayer structures were dissolved into mixed micelles and other structures presenting a wide size distribution.     

PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts.     

Detecting Signatures of Selection Through Haplotype Differentiation Among Hierarchically Structured Populations

The detection of molecular signatures of selection is one of the major concerns of modern population genetics. A widely used strategy in this context is to compare samples from several populations and to look for genomic regions with outstanding genetic differentiation between these populations. Genetic differentiation is generally based on allele frequency differences between populations, which are measured by F_ST or related statistics. Here we introduce a new statistic, denoted hapFLK, which focuses instead on the differences of haplotype frequencies between populations. In contrast to most existing statistics, hapFLK accounts for the hierarchical structure of the sampled populations. Using computer simulations, we show that each of these two features—the use of haplotype information and of the hierarchical structure of populations—significantly improves the detection power of selected loci and that combining them in the hapFLK statistic provides even greater power. We also show that hapFLK is robust with respect to bottlenecks and migration and improves over existing approaches in many situations. Finally, we apply hapFLK to a set of six sheep breeds from Northern Europe and identify seven regions under selection, which include already reported regions but also several new ones. We propose a method to help identifying the population(s) under selection in a detected region, which reveals that in many of these regions selection most likely occurred in more than one population. Furthermore, several of the detected regions correspond to incomplete sweeps, where the favorable haplotype is only at intermediate frequency in the population(s) under selection.     

The Arabidopsis oligopeptidases TOP1 and TOP2 are salicylic acid targets that modulate SA‐mediated signaling and the immune response

Salicylic acid (SA) is a small phenolic molecule with hormonal properties, and is an essential component of the immune response. SA exerts its functions by interacting with protein targets; however, the specific cellular components modulated by SA and critical for immune signal transduction are largely unknown. To uncover cellular activities targeted by SA, we probed Arabidopsis protein microarrays with a functional analog of SA. We demonstrate that thimet oligopeptidases (TOPs) constitute a class of SA‐binding enzymes. Biochemical evidence demonstrated that SA interacts with TOPs and inhibits their peptidase activities to various degrees both in vitro and in plant extracts. Functional characterization of mutants with altered TOP expression indicated that TOP1 and TOP2 mediate SA‐dependent signaling and are necessary for the immune response to avirulent pathogens. Our results support a model whereby TOP1 and TOP2 act in separate pathways to modulate SA‐mediated cellular processes.     

Cellular Source and Mechanisms of High Transcriptome Complexity in the Mammalian Testis

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Intra-Seasonal Flexibility in Avian Metabolic Performance Highlights the Uncoupling of Basal Metabolic Rate and Thermogenic Capacity

Stochastic winter weather events are predicted to increase in occurrence and amplitude at northern latitudes and organisms are expected to cope through phenotypic flexibility. Small avian species wintering in these environments show acclimatization where basal metabolic rate (BMR) and maximal thermogenic capacity (M_SUM) are typically elevated. However, little is known on intra-seasonal variation in metabolic performance and on how population trends truly reflect individual flexibility. Here we report intra-seasonal variation in metabolic parameters measured at the population and individual levels in black-capped chickadees ( Poecile atricapillus ). Results confirmed that population patterns indeed reflect flexibility at the individual level. They showed the expected increase in BMR (6%) and M_SUM (34%) in winter relative to summer but also, and most importantly, that these parameters changed differently through time. BMR began its seasonal increase in November, while M_SUM had already achieved more than 20% of its inter-seasonal increase by October, and declined to its starting level by March, while M_SUM remained high. Although both parameters co-vary on a yearly scale, this mismatch in the timing of variation in winter BMR and M_SUM likely reflects different constraints acting on different physiological components and therefore suggests a lack of functional link between these parameters.