Detecting a genetic bottleneck in Gilbert's Potoroo (Potorous gilbertii) (Marsupialia: Potoroidae), inferred from microsatellite and mitochondrial DNA sequence data

Gilbert's Potoroo isAustralia's most critically endangeredmarsupial, known from a single population inthe Two Peoples Bay National Park in WesternAustralia. We present results from a study ofgenetic variation in microsatellite andmitochondrial DNA. Mean heterozygosity at fivemicrosatellite loci was 49.3%, and the amountof mtDNA variation was extremely low ( =0.0004). There was evidence for a bottleneckin both sets of markers, and this wasconsistent with a demographic decline. Effective population size was estimated usingtwo different models of mutation formicrosatellites (N _e = 243 and 362). The results from this study highlight theconcern for the long-term survival of thisspecies.     

Diabetes slows the recovery from urinary incontinence due to simulated childbirth in female rats

This study was done to test the hypothesis that simulated vaginal birth by vaginal distension (VD) causes more severe urinary incontinence and slower recovery in diabetic rats. After measuring baseline leak point pressure (LPP) in 16 diabetes mellitus (DM) and 16 age- and weight-matched control (Ct) female Sprague-Dawley rats, these animals underwent either VD or sham VD (sham). Four and ten days after the procedures, LPP and conscious cystometry were assessed. Tissues were then harvested and examined by light microscopy. LPP at baseline was equal among all four groups. Four days after VD, LPP in both VD groups dropped to significantly lower levels than in sham rats (P < 0.001). Moreover, LPP in the DM+VD group was significantly lower than in the Ct+VD group. At 10 days, LPP in the Ct+VD group had recovered to its baseline value, whereas the LPP in the DM+VD group remained significantly reduced. DM rats had larger bladder capacity and longer voiding intervals than Ct rats. Histological findings included more severe damage to the external sphincter striated musculature of the urethra in DM+VD group compared with Ct+VD. In conclusion, these findings suggest that DM causes increased severity and delayed functional recovery from the effects of simulated childbirth.     

Bioclipse: an open source workbench for chemo- and bioinformatics

Background  

There is a need for software applications that provide users with a complete and extensible toolkit for chemo- and bioinformatics accessible from a single workbench. Commercial packages are expensive and closed source, hence they do not allow end users to modify algorithms and add custom functionality. Existing open source projects are more focused on providing a framework for integrating existing, separately installed bioinformatics packages, rather than providing user-friendly interfaces. No open source chemoinformatics workbench has previously been published, and no sucessful attempts have been made to integrate chemo- and bioinformatics into a single framework.     

Fast evolutionary genetic differentiation during experimental colonizations

Founder effects during colonization of a novel environment are expected to change the genetic composition of populations, leading to differentiation between the colonizer population and its source population. Another expected outcome is differentiation among populations derived from repeated independent colonizations starting from the same source. We have previously detected significant founder effects affecting rate of laboratory adaptation among Drosophila subobscura laboratory populations derived from the wild. We also showed that during the first generations in the laboratory, considerable genetic differentiation occurs between foundations. The present study deepens that analysis, taking into account the natural sampling hierarchy of six foundations, derived from different locations, different years and from two samples in one of the years. We show that striking stochastic effects occur in the first two generations of laboratory culture, effects that produce immediate differentiation between foundations, independent of the source of origin and despite similarity among all founders. This divergence is probably due to powerful genetic sampling effects during the first few generations of culture in the novel laboratory environment, as a result of a significant drop in N _e. Changes in demography as well as high variance in reproductive success in the novel environment may contribute to the low values of N _e. This study shows that estimates of genetic differentiation between natural populations may be accurate when based on the initial samples collected in the wild, though considerable genetic differentiation may occur in the very first generations of evolution in a new, confined environment. Rapid and significant evolutionary changes can thus occur during the early generations of a founding event, both in the wild and under domestication, effects of interest for both scientific and conservation purposes.     

Kinome-wide interaction modelling using alignment-based and alignment-independent approaches for kinase description and linear and non-linear data analysis techniques

Background  

Protein kinases play crucial roles in cell growth, differentiation, and apoptosis. Abnormal function of protein kinases can lead to many serious diseases, such as cancer. Kinase inhibitors have potential for treatment of these diseases. However, current inhibitors interact with a broad variety of kinases and interfere with multiple vital cellular processes, which causes toxic effects. Bioinformatics approaches that can predict inhibitor-kinase interactions from the chemical properties of the inhibitors and the kinase macromolecules might aid in design of more selective therapeutic agents, that show better efficacy and lower toxicity.     

Of Cattle,Sand Flies and Men: A Systematic Review of Risk Factor Analyses for South Asian Visceral Leishmaniasis and Implications for Elimination

Background

Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent.

Methods and Principal Findings

To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kala-azar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peri-domestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels.

Conclusions

Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed.