A two-neuron system for adaptive goal-directed decision-making in Lymnaea

During goal-directed decision-making, animals must integrate information from the external environment and their internal state to maximize resource localization while minimizing energy expenditure. How this complex problem is solved by the nervous system remains poorly understood. Here, using a combined behavioural and neurophysiological approach, we demonstrate that the mollusc Lymnaea performs a sophisticated form of decision-making during food-searching behaviour, using a core system consisting of just two neuron types. The first reports the presence of food and the second encodes motivational state acting as a gain controller for adaptive behaviour in the absence of food. Using an in vitro analogue of the decision-making process, we show that the system employs an energy management strategy, switching between a low- and high-use mode depending on the outcome of the decision. Our study reveals a parsimonious mechanism that drives a complex decision-making process via regulation of levels of tonic inhibition and phasic excitation

An exploration of social determinants of health amongst internally displaced persons in northern Uganda

Social determinants of health describe the conditions in which people are born, grow, live, work and age and their influence on health. These circumstances are shaped by the distribution of money, power and resources at global, national and local levels, which are themselves influenced by policy choices. Armed conflict and forced displacement are important influences on the social determinants of health. There is limited evidence on the social determinants of health of internally displaced persons (IDPs) who have been forced from their homes due to armed conflict but remain within the borders of their country. The aim of this study was to explore the social determinants of overall physical and mental health of IDPs, including the response strategies used by IDPs to support their health needs. Northern Uganda was chosen as a case-study, and 21 face-to-face semi-structured interviews with IDPs were conducted in fifteen IDP camps between November and December 2006

Monitoring microbicide gel use with real-time notification of the container’s opening events : results of the CAPRISA Wisebag study.

CAPRISA, 2014.Accurate estimation of the effectiveness of a microbicide for HIV prevention requires valid measurement of adherence to product use. A microbicide gel applicator container (Wisebag), fitted with cell phone technology to transmit opening events and text message reminders, was developed to monitor each opening event of the container as a proxy for gel use and adherence. Ten women were enrolled in a pilot study and followed for up to 4 months. Wisebag opening (WBO) dates and times were recorded and correlated with self-reported sex acts and gel applicator returns. During the 33 monthly follow-up visits, 47.8% (77/161) of the recorded number of WBO events were concordant with the number of empty (used) applicators returned. The discrepancies were likely due to removal of more than one applicator during a single opening event. When the date and time of the WBO event data was assessed in relation to three different self-report adherence measures, agreement was fairly modest. The Wisebag was found to be acceptable as a storage container and the cell phone reminders generated were useful in supporting the dosing strategy. We recommend that the Wisebag be considered for larger scale and lengthier testing in microbicide trials

Gene Expression Profiles of Colonic Mucosa in Healthy Young Adult and Senior Dogs

Background: We have previously reported the effects of age and diet on nutrient digestibility, intestinal morphology, and large intestinal fermentation patterns in healthy young adult and senior dogs. However, a genome-wide molecular analysis of colonic mucosa as a function of age and diet has not yet been performed in dogs. Methodology/Principal Findings: Colonic mucosa samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed one of two diets (animal protein-based vs. plant protein-based) for 12 months. Total RNA in colonic mucosa was extracted and hybridized to Affymetrix GeneChipH Canine Genome Arrays. Results indicated that the majority of gene expression changes were due to age (212 genes) rather than diet (66 genes). In particular, the colonic mucosa of senior dogs had increased expression of genes associated with cell proliferation, inflammation, stress response, and cellular metabolism, whereas the expression of genes associated with apoptosis and defensive mechanisms were decreased in senior vs. young adult dogs. No consistent diet-induced alterations in gene expression existed in both age groups, with the effects of diet being more pronounced in senior dogs than in young adult dogs. Conclusion: Our results provide molecular insight pertaining to the aged canine colon and its predisposition to dysfunction and disease. Therefore, our data may aid in future research pertaining to age-associated gastrointestinal physiologica

Population genomics of speciation and admixture

The application of population genomics to the understanding of speciation has led to the emerging field of speciation genomics. This has brought new insight into how divergence builds up within the genome during speciation and is also revealing the extent to which species can continue to exchange genetic material despite reproductive barriers. It is also providing powerful new approaches for linking genotype to phenotype in admixed populations. In this chapter, we give an overview of some of the methods that have been used and some of the novel insights gained. We also outline some of the pitfalls of the most commonly used methods and possible problems with interpretation of the results

Holding it together: rapid evolution and positive selection in the synaptonemal complex of Drosophila

Background The synaptonemal complex (SC) is a highly conserved meiotic structure that functions to pair homologs and facilitate meiotic recombination in most eukaryotes. Five Drosophila SC proteins have been identified and localized within the complex: C(3)G, C(2)M, CONA, ORD, and the newly identified Corolla. The SC is required for meiotic recombination in Drosophila and absence of these proteins leads to reduced crossing over and chromosomal nondisjunction. Despite the conserved nature of the SC and the key role that these five proteins have in meiosis in D. melanogaster, they display little apparent sequence conservation outside the genus. To identify factors that explain this lack of apparent conservation, we performed a molecular evolutionary analysis of these genes across the Drosophila genus. Results For the five SC components, gene sequence similarity declines rapidly with increasing phylogenetic distance and only ORD and C(2)M are identifiable outside of the Drosophila genus. SC gene sequences have a higher dN/dS (ω) rate ratio than the genome wide average and this can in part be explained by the action of positive selection in almost every SC component. Across the genus, there is significant variation in ω for each protein. It further appears that ω estimates for the five SC components are in accordance with their physical position within the SC. Components interacting with chromatin evolve slowest and components comprising the central elements evolve the most rapidly. Finally, using population genetic approaches, we demonstrate that positive selection on SC components is ongoing. Conclusions SC components within Drosophila show little apparent sequence homology to those identified in other model organisms due to their rapid evolution. We propose that the Drosophila SC is evolving rapidly due to two combined effects. First, we propose that a high rate of evolution can be partly explained by low purifying selection on protein components whose function is to simply hold chromosomes together. We also propose that positive selection in the SC is driven by its sex-specificity combined with its role in facilitating both recombination and centromere clustering in the face of recurrent bouts of drive in female meiosis

Review of methods used by chiropractors to determine the site for applying manipulation

Background: With the development of increasing evidence for the use of manipulation in the management of musculoskeletal conditions, there is growing interest in identifying the appropriate indications for care. Recently, attempts have been made to develop clinical prediction rules, however the validity of these clinical prediction rules remains unclear and their impact on care delivery has yet to be established. The current study was designed to evaluate the literature on the validity and reliability of the more common methods used by doctors of chiropractic to inform the choice of the site at which to apply spinal manipulation. Methods: Structured searches were conducted in Medline, PubMed, CINAHL and ICL, supported by hand searches of archives, to identify studies of the diagnostic reliability and validity of common methods used to identify the site of treatment application. To be included, studies were to present original data from studies of human subjects and be designed to address the region or location of care delivery. Only English language manuscripts from peer-reviewed journals were included. The quality of evidence was ranked using QUADAS for validity and QAREL for reliability, as appropriate. Data were extracted and synthesized, and were evaluated in terms of strength of evidence and the degree to which the evidence was favourable for clinical use of the method under investigation. Results: A total of 2594 titles were screened from which 201 articles met all inclusion criteria. The spectrum of manuscript quality was quite broad, as was the degree to which the evidence favoured clinical application of the diagnostic methods reviewed. The most convincing favourable evidence was for methods which confirmed or provoked pain at a specific spinal segmental level or region. There was also high quality evidence supporting the use, with limitations, of static and motion palpation, and measures of leg length inequality. Evidence of mixed quality supported the use, with limitations, of postural evaluation. The evidence was unclear on the applicability of measures of stiffness and the use of spinal x-rays. The evidence was of mixed quality, but unfavourable for the use of manual muscle testing, skin conductance, surface electromyography and skin temperature measurement. Conclusions: A considerable range of methods is in use for determining where in the spine to administer spinal manipulation. The currently published evidence falls across a spectrum ranging from strongly favourable to strongly unfavourable in regard to using these methods. In general, the stronger and more favourable evidence is for those procedures which take a direct measure of the presumptive site of care– methods involving pain provocation upon palpation or localized tissue examination. Procedures which involve some indirect assessment for identifying the manipulable lesion of the spine–such as skin conductance or thermography–tend not to be supported by the available evidence.https://doi.org/10.1186/2045-709X-21-3

The effects of purifying selection on patterns of genetic differentiation between Drosophila melanogaster populations.

Using the data provided by the Drosophila Population Genomics Project, we investigate factors that affect the genetic differentiation between Rwandan and French populations of D. melanogaster. By examining within-population polymorphisms, we show that sites in long introns (especially those >2000 bp) have significantly lower π (nucleotide diversity) and more low-frequency variants (as measured by Tajima's D, minor allele frequencies, and prevalence of variants that are private to one of the two populations) than short introns, suggesting a positive relationship between intron length and selective constraint. A similar analysis of protein-coding polymorphisms shows that 0-fold (degenerate) sites in more conserved genes are under stronger purifying selection than those in less conserved genes. There is limited evidence that selection on codon bias has an effect on differentiation (as measured by FST) at 4-fold (degenerate) sites, and 4-fold sites and sites in 8-30 bp of short introns ⩽65 bp have comparable FST values. Consistent with the expected effect of purifying selection, sites in long introns and 0-fold sites in conserved genes are less differentiated than those in short introns and less conserved genes, respectively. Genes in non-crossover regions (for example, the fourth chromosome) have very high FST values at both 0-fold and 4-fold degenerate sites, which is probably because of the large reduction in within-population diversity caused by tight linkage between many selected sites. Our analyses also reveal subtle statistical properties of FST, which arise when information from multiple single nucleotide polymorphisms is combined and can lead to the masking of important signals of selection