Molecular phylogeny and timing of diversification in Alpine Rhithrogena (Ephemeroptera: Heptageniidae).

BACKGROUND: Larvae of the Holarctic mayfly genus Rhithrogena Eaton, 1881 (Ephemeroptera, Heptageniidae) are a diverse and abundant member of stream and river communities and are routinely used as bio-indicators of water quality. Rhithrogena is well diversified in the European Alps, with a number of locally endemic species, and several cryptic species have been recently detected. While several informal species groups are morphologically well defined, a lack of reliable characters for species identification considerably hampers their study. Their relationships, origin, timing of speciation and mechanisms promoting their diversification in the Alps are unknown. RESULTS: Here we present a species-level phylogeny of Rhithrogena in Europe using two mitochondrial and three nuclear gene regions. To improve sampling in a genus with many cryptic species, individuals were selected for analysis according to a recent DNA-based taxonomy rather than traditional nomenclature. A coalescent-based species tree and a reconstruction based on a supermatrix approach supported five of the species groups as monophyletic. A molecular clock, mapped on the most resolved phylogeny and calibrated using published mitochondrial evolution rates for insects, suggested an origin of Alpine Rhithrogena in the Oligocene/Miocene boundary. A diversification analysis that included simulation of missing species indicated a constant speciation rate over time, rather than any pronounced periods of rapid speciation. Ancestral state reconstructions provided evidence for downstream diversification in at least two species groups. CONCLUSIONS: Our species-level analyses of five gene regions provide clearer definitions of species groups within European Rhithrogena. A constant speciation rate over time suggests that the paleoclimatic fluctuations, including the Pleistocene glaciations, did not significantly influence the tempo of diversification of Alpine species. A downstream diversification trend in the hybrida and alpestris species groups supports a previously proposed headwater origin hypothesis for aquatic insects

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Growing old with the immune system: a study of immunosenescence in the zebra finch (Taeniopygia guttata)

Immunosenescence has not received much attention in birds and the few existing studies indicate that the occurrence of immunosenescence and/or its extent may differ between species. In addition, not much information is available on the immunosenescence patterns of different immune parameters assessed simultaneously in both sexes within a single species. The present study reports the results on immunosenescence in innate immunity and both cellular and humoral acquired immunity of both sexes in a captive population of zebra finch (Taeniopygia guttata) using three age groups (approximately 0.2, 2.5 and 5.1 years). Both male and female finches showed an inverse U-shaped pattern in cellular immune function with age, quantified by a PHA response. Males showed stronger responses than females at all ages. In contrast, an increase with age in humoral immunity, quantified through total plasma immunoglobulin Y levels, was found in both sexes. However, our measurements of innate immunity measured through the bacteria-killing ability against Escherichia coli gave inconclusive results. Still, we conclude that both cellular and humoral acquired immunity are susceptible to immunosenescence, and that the sexes differ in cellular immunity

Competitive Asymmetries in the Use of Supplementary Food by the Endangered Iberian Lynx (Lynx pardinus)

Background: As a conservation tool, supplementary feeding programs may be directed to specific individuals or sectors of the target population whose productivity or survival is thought to be limited by food scarcity. However, the use of supplemental food by different sex and age classes has received little attention. We studied individual variation in the access of the endangered Iberian lynx (Lynx pardinus) to supplementary food. Methodology/Principal Findings: From 5349 pictures taken with automatic cameras placed in 25 feeding stations, we identified 28 individuals whose sex and age were known. All individuals known to live in areas subjected to supplementation regularly visited feeding stations. Food consumption was not proportional to expected variations in energy demand within sex and age classes. Food consumption by males was higher than by females, and increased with age, in agreement with a despotic distribution. Food consumption also increased with lynx body mass, and this pattern held for individuals sharing the same breeding territories. The access of inferior competitors increased with the number of feeding stations available within lynx territories. Conclusions/Significance: All lynx exposed to food supplementation made a regular use of extra food but individuals predicted to be competitively dominant visited stations more frequently than subordinates of the same breeding territory. Our results suggest that insufficient provision of supplementary food could restrict the access of juveniles, or even adult females, to feeding stations. Limited consumption by these target individuals may compromise the efficiency of the supplementary feeding programme at the population level, in endangered species that, as the Iberian lynx, exhibit marked sexual dimorphism in body size.Peer reviewe

Compensatory Development and Costs of Plasticity: Larval Responses to Desiccated Conspecifics

Understanding constraints on phenotypic plasticity is central to explaining its evolution and the evolution of phenotypes in general, yet there is an ongoing debate on the classification and relationships among types of constraints. Since plasticity is often a developmental process, studies that consider the ontogeny of traits and their developmental mechanisms are beneficial. We manipulated the timing and reliability of cues perceived by fire salamander larvae for the future desiccation of their ephemeral pools to determine whether flexibility in developmental rates is constrained to early ontogeny. We hypothesized that higher rates of development, and particularly compensation for contradictory cues, would incur greater endogenous costs. We found that larvae respond early in ontogeny to dried conspecifics as a cue for future desiccation, but can fully compensate for this response in case more reliable but contradictory cues are later perceived. Patterns of mortality suggested that endogenous costs may depend on instantaneous rates of development, and revealed asymmetrical costs of compensatory development between false positive and false negative early information. Based on the results, we suggest a simple model of costs of development that implies a tradeoff between production costs of plasticity and phenotype-environment mismatch costs, which may potentially underlie the phenomenon of ontogenetic windows constraining plasticity

Specificity of DNA-binding by the FAX-1 and NHR-67 nuclear receptors of Caenorhabditis elegans is partially mediated via a subclass-specific P-box residue

<p>Abstract</p> <p>Background</p> <p>The nuclear receptors of the NR2E class play important roles in pattern formation and nervous system development. Based on a phylogenetic analysis of DNA-binding domains, we define two conserved groups of orthologous NR2E genes: the NR2E1 subclass, which includes <it>C. elegans nhr-67, Drosophila tailless </it>and <it>dissatisfaction</it>, and vertebrate Tlx (NR2E2, NR2E4, NR2E1), and the NR2E3 subclass, which includes <it>C. elegans fax-1 </it>and vertebrate PNR (NR2E5, NR2E3). PNR and Tll nuclear receptors have been shown to bind the hexamer half-site AAGTCA, instead of the hexamer AGGTCA recognized by most other nuclear receptors, suggesting unique DNA-binding properties for NR2E class members.</p> <p>Results</p> <p>We show that NR2E3 subclass member FAX-1, unlike NHR-67 and other NR2E1 subclass members, binds to hexamer half-sites with relaxed specificity: it will bind hexamers with the sequence ANGTCA, although it prefers a purine to a pyrimidine at the second position. We use site-directed mutagenesis to demonstrate that the difference between FAX-1 and NHR-67 binding preference is partially mediated by a conserved subclass-specific asparagine or aspartate residue at position 19 of the DNA-binding domain. This amino acid position is part of the "P box" that plays a critical role in defining binding site specificity and has been shown to make hydrogen-bond contacts to the second position of the hexamer in co-crystal structures for other nuclear receptors. The relaxed specificity allows FAX-1 to bind a much larger repertoire of half-sites than NHR-67. While NR2E1 class proteins bind both monomeric and dimeric sites, the NR2E3 class proteins bind only dimeric sites. The presence of a single strong site adjacent to a very weak site allows dimeric FAX-1 binding, further increasing the number of dimeric binding sites to which FAX-1 may bind <it>in vivo</it>.</p> <p>Conclusion</p> <p>These findings identify subclass-specific DNA-binding specificities and dimerization properties for the NR2E1 and NR2E3 subclasses. For the NR2E1 protein NHR-67, Asp-19 permits binding to AAGTCA half-sites, while Asn-19 permits binding to AGGTCA half-sites. The apparent conservation of DNA-binding properties between vertebrate and nematode NR2E receptors allows for the possibility of evolutionarily-conserved regulatory patterns.</p

Differential Effects of Early- and Late-Life Access to Carotenoids on Adult Immune Function and Ornamentation in Mallard Ducks (Anas platyrhynchos)

Environmental conditions early in life can affect an organism’s phenotype at adulthood, which may be tuned to perform optimally in conditions that mimic those experienced during development (Environmental Matching hypothesis), or may be generally superior when conditions during development were of higher quality (Silver Spoon hypothesis). Here, we tested these hypotheses by examining how diet during development interacted with diet during adulthood to affect adult sexually selected ornamentation and immune function in male mallard ducks (Anas platyrhynchos). Mallards have yellow, carotenoid-pigmented beaks that are used in mate choice, and the degree of beak coloration has been linked to adult immune function. Using a 2×2 factorial experimental design, we reared mallards on diets containing either low or high levels of carotenoids (nutrients that cannot be synthesized de novo) throughout the period of growth, and then provided adults with one of these two diets while simultaneously quantifying beak coloration and response to a variety of immune challenges. We found that both developmental and adult carotenoid supplementation increased circulating carotenoid levels during dietary treatment, but that birds that received low-carotenoid diets during development maintained relatively higher circulating carotenoid levels during an adult immune challenge. Individuals that received low levels of carotenoids during development had larger phytohemagglutinin (PHA)-induced cutaneous immune responses at adulthood; however, dietary treatment during development and adulthood did not affect antibody response to a novel antigen, nitric oxide production, natural antibody levels, hemolytic capacity of the plasma, or beak coloration. However, beak coloration prior to immune challenges positively predicted PHA response, and strong PHA responses were correlated with losses in carotenoid-pigmented coloration. In sum, we did not find consistent support for either the Environmental Matching or Silver Spoon hypotheses. We then describe a new hypothesis that should be tested in future studies examining developmental plasticity

Frailty Intervention Trial (FIT)

<p>Abstract</p> <p>Background</p> <p>Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity). Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty.</p> <p>We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people.</p> <p>Methods and Design</p> <p>A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period.</p> <p>Discussion</p> <p>This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation. The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trails Registry: ACTRN12608000250336.</p

Genome-Wide Analysis Reveals a Major Role in Cell Fate Maintenance and an Unexpected Role in Endoreduplication for the Drosophila FoxA Gene Fork Head

Transcription factors drive organogenesis, from the initiation of cell fate decisions to the maintenance and implementation of these decisions. The Drosophila embryonic salivary gland provides an excellent platform for unraveling the underlying transcriptional networks of organ development because Drosophila is relatively unencumbered by significant genetic redundancy. The highly conserved FoxA family transcription factors are essential for various aspects of organogenesis in all animals that have been studied. Here, we explore the role of the single Drosophila FoxA protein Fork head (Fkh) in salivary gland organogenesis using two genome-wide strategies. A large-scale in situ hybridization analysis reveals a major role for Fkh in maintaining the salivary gland fate decision and controlling salivary gland physiological activity, in addition to its previously known roles in morphogenesis and survival. The majority of salivary gland genes (59%) are affected by fkh loss, mainly at later stages of salivary gland development. We show that global expression of Fkh cannot drive ectopic salivary gland formation. Thus, unlike the worm FoxA protein PHA-4, Fkh does not function to specify cell fate. In addition, Fkh only indirectly regulates many salivary gland genes, which is also distinct from the role of PHA-4 in organogenesis. Our microarray analyses reveal unexpected roles for Fkh in blocking terminal differentiation and in endoreduplication in the salivary gland and in other Fkh-expressing embryonic tissues. Overall, this study demonstrates an important role for Fkh in determining how an organ preserves its identity throughout development and provides an alternative paradigm for how FoxA proteins function in organogenesis

Repurposing NGO data for better research outcomes: A scoping review of the use and secondary analysis of NGO data in health policy and systems research

Background Non-government organisations (NGOs) collect and generate vast amounts of potentially rich data, most of which are not used for research purposes. Secondary analysis of NGO data (their use and analysis in a study for which they were not originally collected) presents an important but largely unrealised opportunity to provide new research insights in critical areas including the evaluation of health policy and programmes. Methods A scoping review of the published literature was performed to identify the extent to which secondary analysis of NGO data has been used in health policy and systems research (HPSR). A tiered analytic approach provided a comprehensive overview and descriptive analyses of the studies which: 1) used data produced or collected by or about NGOs; 2) performed secondary analysis of the NGO data (beyond use of an NGO report as a supporting reference); 3) used NGO-collected clinical data. Results Of the 156 studies which performed secondary analysis of NGO-produced or collected data, 64% (n=100) used NGO-produced reports (e.g. to critique NGO activities and as a contextual reference) and 8% (n=13) analysed NGO-collected clinical data.. Of the studies, 55% investigated service delivery research topics, with 48% undertaken in developing countries and 17% in both developing and developed. NGO-collected clinical data enabled HPSR within marginalised groups (e.g. migrants, people in conflict-affected areas), with some limitations such as inconsistencies and missing data. Conclusion We found evidence that NGO-collected and produced data are most commonly perceived as a source of supporting evidence for HPSR and not as primary source data. However, these data can facilitate research in under-researched marginalised groups and in contexts that are hard to reach by academics, such as conflict-affected areas. NGO–academic collaboration could help address issues of NGO data quality to facilitate their more widespread use in research. Their use could enable relevant and timely research in the areas of health policy, programme evaluation and advocacy to improve health and reduce health inequalities, especially in marginalised groups and developing countries