Sexually dimorphic role for vasopressin in the development of social play

Despite the well-established role of vasopressin (AVP) in adult social behavior, its role in social development is relatively unexplored. In this paper, we focus on the most prominent social behavior of juvenile rats, social play. Previous pharmacological experiments in our laboratory suggested that AVP regulates play in a sex- and brain region-specific manner in juvenile rats. Here we investigate the role of specific AVP systems in the emergence of social play. We first characterize the development of play in male and female Wistar rats and then ask whether the development of AVP mRNA expression correlates with the emergence of play. Unexpectedly, play emerged more rapidly in weanling-aged females than in males, resulting in a sex difference opposite of that typically reported for older, juvenile rats. AVP mRNA and play were correlated in males only, with a negative correlation in the bed nucleus of the stria terminalis and a positive correlation in the paraventricular nucleus of the hypothalamus. These findings support the hypothesis that AVP acts differentially on multiple systems in a sex-specific manner to regulate social play and suggest a role for PVN and BNST AVP systems in the development of play. Differential neuropeptide regulation of male and female social development may underlie well-documented sex differences in incidence, progression, and symptom severity of behavioral disorders during development

The Cytotoxic T Lymphocyte Antigen-4+49A/G Single Nucleotide Polymorphism Association With Visceral Leishmaniasis

Background: Several lines of evidence approve that innate and adaptive immunity play key roles in the defense against visceral leishmaniasis (VL). The polymorphism within the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene alters its expression. Objectives: The main aim of this study was to evaluate the polymorphism within the +49 position of the CTLA-4 gene of Iranian patients with VL in comparison with healthy controls. Materials and Methods: In this cross-sectional study, 88 patients with clinical presentations of VL, who were seropositive for Leishmania (group 1), 86 patients without clinical presentations but seropositive (group 2), and 115 healthy controls (group 3) were assessed with respect to the CTLA-4 +49A/G polymorphism, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The anti-Leishmania antibody titration was evaluated using an immunofluorescence method. Results: Our results indicated that both CTLA-4 +49A/G polymorphisms were significantly associated with VL. Conclusions: According to the results, the polymorphisms within the +49 position of CTLA-4 can be associated with VL and may be considered as risk factors for the disease

Predation on Multiple Prey Types Across a Disturbance Gradient in Tropical Montane Forests of Peninsular Malaysia

Predation plays a critical role in animal and plant survivorship, and can be highly sensitive to habitat loss and disturbance. Tropical montane forests in Southeast Asia are being modified rapidly by land-use change, and the consequences of this on predation likelihood are poorly understood. In Peninsular Malaysia, we conducted predation experiments at eight tropical montane forest sites along a disturbance gradient. We investigated whether (1) predation pressure in primary forests differs between different mountains; (2) predation probability is linked to habitat degradation; and (3) vegetation variables explain predation occurrence. At each forest site, we placed artificial nests with real and model quail eggs, dishes with real and artificial seeds of the cempedak (Artocarpus champeden), models resembling four-lined tree frogs (Polypedetes leucomystax) and models of the late instar caterpillar of the common Mormon (Papilio polytes) at points 100 m apart for three nights. Using Bayesian binomial simulations, we showed that predation likelihood in primary forests from different mountains can vary (e.g., probability of the difference in predation rate of artificial caterpillars between two primary forests was estimated at 82–100%). We also found that higher predation was not linked to habitat degradation for all artificial prey and seeds (e.g., comparing forests of varying degrees of disturbance from the same mountain, the probability that predation of an artificial caterpillar is lower at the primary forest was estimated at 2–20% only). Model selection and hierarchical partitioning showed that vegetation variables can explain predation occurrence, suggesting microhabitat characteristics may be influential. Conducting predation experiments by using artificial prey and seeds is useful for comparing predation likelihood at different sites, making ecological comparisons, and for informing conservation decisions. This novel approach of using multiple prey items also showed that predation for each can vary and thus caution against deploying a single prey type to draw broad inferences of predation in degraded systems

Ultra-endurance athletic performance suggests that energetics drive human morphological thermal adaptation

Both extinct and extant hominin populations display morphological features consistent with Bergmann's and Allen's Rules. However, the functional implications of the morphologies described by these ecological laws are poorly understood. We examined this through the lens of endurance running. Previous research concerning endurance running has focused on locomotor energetic economy. We considered a less-studied dimension of functionality, thermoregulation. The performance of male ultra-marathon runners (n = 88) competing in hot and cold environments was analysed with reference to expected thermoregulatory energy costs and the optimal morphologies predicted by Bergmann's and Allen's Rules. Ecogeographical patterning supporting both principles was observed in thermally challenging environments. Finishers of hot-condition events had significantly longer legs than finishers of cold-condition events. Furthermore, hot-condition finishers had significantly longer legs than those failing to complete hot-condition events. A degree of niche-picking was evident; athletes may have tailored their event entry choices in accordance with their previous race experiences. We propose that the interaction between prolonged physical exertion and hot or cold climates may induce powerful selective pressures driving morphological adaptation. The resulting phenotypes reduce thermoregulatory energetic expenditure, allowing diversion of energy to other functional outcomes such as faster running

Opportunities for improving pLDH-based malaria diagnostic tests

<p>Abstract</p> <p>Background</p> <p>Monoclonal antibodies to <it>Plasmodium </it>lactate dehydrogenase (pLDH) have been previously used to format immunochromatographic tests for the diagnosis of malaria. Using pLDH as an antigen has several advantages as a sensitive measure of the presence of parasites within patient blood samples. However, variable results in terms of specificity and sensitivity among different commercially available diagnostic kits have been reported and it has not been clear from these studies whether the performance of an individual test is due simply to how it is engineered or whether it is due to the biochemical nature of the pLDH-antibody reaction itself.</p> <p>Methods</p> <p>A series of systematic studies to determine how various pLDH monoclonal antibodies work in combination was undertaken. Different combinations of anti-pLDH monoclonal antibodies were used in a rapid-test immunochromatographic assay format to determine parameters of sensitivity and specificity with regard to individual <it>Plasmodium </it>species.</p> <p>Results</p> <p>Dramatic differences were found in both species specificity and overall sensitivity depending on which antibody is used on the immunochromatographic strip and which is used on the colorimetric colloidal-gold used for visual detection.</p> <p>Discussion</p> <p>The results demonstrate the feasibility of different test formats for the detection and speciation of malarial infections. In addition, the data will enable the development of a universal rapid test algorithm that may potentially provide a cost-effective strategy to diagnose and manage patients in a wide range of clinical settings.</p> <p>Conclusion</p> <p>These data emphasize that using different anti-pLDH antibody combinations offers a tractable way to optimize immunochromatographic pLDH tests.</p

Low Maternal Capital Predicts Life History Trade-Offs in Daughters: Why Adverse Outcomes Cluster in Individuals.

Background: Some individuals appear prone to multiple adverse outcomes, including poor health, school dropout, risky behavior and early reproduction. This clustering remains poorly understood. Drawing on evolutionary life history theory, we hypothesized that maternal investment in early life would predict the developmental trajectory and adult phenotype of female offspring. Specifically, we predicted that daughters receiving low investment would prioritize the life history functions of "reproduction" and "defense" over "growth" and "maintenance," increasing the risk of several adverse outcomes. Methods: We investigated 2,091 mother-daughter dyads from a birth cohort in Pelotas, Brazil. We combined data on maternal height, body mass index, income, and education into a composite index of "maternal capital." Daughter outcomes included reproductive status at 18 years, growth, adult anthropometry, body composition, cardio-metabolic risk, educational attainment, work status, and risky behavior. We tested whether daughters' early reproduction (<18 years) and exposure to low maternal capital were associated with adverse outcomes, and whether this accounted for the clustering of adverse outcomes within individuals. Results: Daughters reproducing early were shorter, more centrally adipose, had less education and demonstrated more risky behavior compared to those not reproducing. Low maternal capital was associated with greater likelihood of the daughter reproducing early, smoking and having committed violent crime. High maternal capital was positively associated with the daughter's birth weight and adult size, and the likelihood of being in school. Associations of maternal capital with cardio-metabolic risk were inconsistent. Daughters reproducing early comprised 14.8% of the population, but accounted for 18% of obesity; 20% of violent crime, low birth weight and short stature; 32% of current smoking; and 52% of school dropout. Exposure to low maternal capital contributed similarly to the clustering of adverse outcomes among daughters. Outcomes were worst among daughters characterized by both low maternal capital and early reproduction. Conclusion: Consistent with life history theory, daughters exposed to low maternal capital demonstrate "future discounting" in behavior and physiology, prioritizing early reproduction over growth, education, and health. Trade-offs associated with low maternal capital and early reproduction contribute to clustering of adverse outcomes. Our approach provides new insight into inter-generational cycles of disadvantage

Using interpretative phenomenological analysis to inform physiotherapy practice: An introduction with reference to the lived experience of cerebellar ataxia

The attached file is a pre-published version of the full and final paper which can be found at the link below.This article has been made available through the Brunel Open Access Publishing Fund.Qualitative research methods that focus on the lived experience of people with health conditions are relatively underutilised in physiotherapy research. This article aims to introduce interpretative phenomenological analysis (IPA), a research methodology oriented toward exploring and understanding the experience of a particular phenomenon (e.g., living with spinal cord injury or chronic pain, or being the carer of someone with a particular health condition). Researchers using IPA try to find out how people make sense of their experiences and the meanings they attach to them. The findings from IPA research are highly nuanced and offer a fine grained understanding that can be used to contextualise existing quantitative research, to inform understanding of novel or underresearched topics or, in their own right, to provoke a reappraisal of what is considered known about a specified phenomenon. We advocate IPA as a useful and accessible approach to qualitative research that can be used in the clinical setting to inform physiotherapy practice and the development of services from the perspective of individuals with particular health conditions.This article is available through the Brunel Open Access Publishing Fund

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice

Accuracy of Malaria Rapid Diagnostic Tests in Community Studies and their Impact on Treatment of Malaria in an Area with Declining Malaria Burden in North-Eastern Tanzania.

Despite some problems related to accuracy and applicability of malaria rapid diagnostic tests (RDTs), they are currently the best option in areas with limited laboratory services for improving case management through parasitological diagnosis and reducing over-treatment. This study was conducted in areas with declining malaria burden to assess; 1) the accuracy of RDTs when used at different community settings, 2) the impact of using RDTs on anti-malarial dispensing by community-owned resource persons (CORPs) and 3) adherence of CORPs to treatment guidelines by providing treatment based on RDT results. Data were obtained from: 1) a longitudinal study of passive case detection of fevers using CORPs in six villages in Korogwe; and 2) cross-sectional surveys (CSS) in six villages of Korogwe and Muheza districts, north-eastern, Tanzania. Performance of RDTs was compared with microscopy as a gold standard, and factors affecting their accuracy were explored using a multivariate logistic regression model. Overall sensitivity and specificity of RDTs in the longitudinal study (of 23,793 febrile cases; 18,154 with microscopy and RDTs results) were 88.6% and 88.2%, respectively. In the CSS, the sensitivity was significantly lower (63.4%; χ2=367.7, p<0.001), while the specificity was significantly higher (94.3%; χ2=143.1, p<0.001) when compared to the longitudinal study. As determinants of sensitivity of RDTs in both studies, parasite density of<200 asexual parasites/μl was significantly associated with high risk of false negative RDTs (OR≥16.60, p<0.001), while the risk of false negative test was significantly lower among cases with fever (axillary temperature ≥37.5 °C) (OR≤0.63, p≤0.027). The risk of false positive RDT (as a determinant of specificity) was significantly higher in cases with fever compared to afebrile cases (OR≥2.40, p<0.001). Using RDTs reduced anti-malarials dispensing from 98.9% to 32.1% in cases aged ≥5 years. Although RDTs had low sensitivity and specificity, which varied widely depending on fever and parasite density, using RDTs reduced over-treatment with anti-malarials significantly. Thus, with declining malaria prevalence, RDTs will potentially identify majority of febrile cases with parasites and lead to improved management of malaria and non-malaria fevers