Monoclonal antibody Py recognizes neurofilament heavy chain and is a selective marker for large diameter neurons in the brain Brain Structure and Function

Almost 30 years ago, the monoclonal antibody Py was developed to detect pyramidal neurons in the CA3 region of the rat hippocampus. The utility of this antibody quickly expanded when several groups discovered that it could be used to identify very specific populations of neurons in the normal, developing, and diseased or injured central nervous system. Despite this body of literature, the identity of the antigen that the Py antibody recognizes remained elusive. Here, immunoprecipitation experiments from the adult rat cortex identified the Py antigen as neurofilament heavy chain (NF-H). Double immunolabeling of sections through the rat brain using Py and NF-H antibodies confirmed the identity of the Py antigen, and reveal that Py/NF-H+ neurons appear to share the feature of being particularly large in diameter. These include the neurons of the gigantocellular reticular formation, pyramidal neurons of layers II/III and V of the cortex, cerebellar Purkinje neurons as well as CA3 pyramidal neurons. Taken together, this finding gives clarity to past work using the monoclonal Py antibody, and immediately expands our understanding of the importance of NF-H in neural development, functioning, and disease

Modelling the control of bovine brucellosis in India.

Brucellosis imposes substantial impacts on livestock production and public health worldwide. A stochastic, age-structured model incorporating herd demographics was developed describing within- and between-herd transmission of Brucella abortus in dairy cattle herds. The model was fitted to data from a cross-sectional study conducted in Punjab State of India and used to evaluate the effectiveness of control strategies under consideration. Based on model results, stakeholder acceptance and constraints regarding vaccine supply, vaccination of replacement calves in large farms should be prioritized. Test and removal applied at early stages of the control programme where seroprevalence is high would not constitute an effective or acceptable use of resources because significant numbers of animals would be 'removed' (culled or not used for breeding) based on false positive results. To achieve sustained reductions in brucellosis, policymakers must commit to maintaining vaccination in the long term, which may eventually reduce frequency of infection in the livestock reservoir to a low enough level for elimination to be a realistic objective. This work provides key strategic insights into the control of brucellosis in India, which has the largest cattle population globally, and a general modelling framework for evaluating control strategies in endemic settings

Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy

Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defects in heart tissue from the Taiwanese mouse model of severe SMA. We identify increased levels of lamin A/C as a robust molecular phenotype in the heart of SMA mice and show that lamin A/C dysregulation is also apparent in SMA patient fibroblast cells and other tissues from SMA mice. Lamin A/C expression was regulated in vitro by knockdown of the E1 ubiquitination factor ubiquitin-like modifier activating enzyme 1, a key downstream mediator of SMN-dependent disease pathways, converging on β-catenin signaling. Increased levels of lamin A are known to increase the rigidity of nuclei, inevitably disrupting contractile activity in cardiomyocytes. The increased lamin A/C levels in the hearts of SMA mice therefore provide a likely mechanism explaining morphological and functional cardiac defects, leading to blood pooling. Therapeutic strategies directed at lamin A/C may therefore offer a new approach to target cardiac pathology in SMA

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

Ecological equivalence: a realistic assumption for niche theory as a testable alternative to neutral theory

Hubbell's 2001 neutral theory unifies biodiversity and biogeography by modelling steady-state distributions of species richness and abundances across spatio-temporal scales. Accurate predictions have issued from its core premise that all species have identical vital rates. Yet no ecologist believes that species are identical in reality. Here I explain this paradox in terms of the ecological equivalence that species must achieve at their coexistence equilibrium, defined by zero net fitness for all regardless of intrinsic differences between them. I show that the distinction of realised from intrinsic vital rates is crucial to evaluating community resilience. An analysis of competitive interactions reveals how zero-sum patterns of abundance emerge for species with contrasting life-history traits as for identical species. I develop a stochastic model to simulate community assembly from a random drift of invasions sustaining the dynamics of recruitment following deaths and extinctions. Species are allocated identical intrinsic vital rates for neutral dynamics, or random intrinsic vital rates and competitive abilities for niche dynamics either on a continuous scale or between dominant-fugitive extremes. Resulting communities have steady-state distributions of the same type for more or less extremely differentiated species as for identical species. All produce negatively skewed log-normal distributions of species abundance, zero-sum relationships of total abundance to area, and Arrhenius relationships of species to area. Intrinsically identical species nevertheless support fewer total individuals, because their densities impact as strongly on each other as on themselves. Truly neutral communities have measurably lower abundance/area and higher species/abundance ratios. Neutral scenarios can be parameterized as null hypotheses for testing competitive release, which is a sure signal of niche dynamics. Ignoring the true strength of interactions between and within species risks a substantial misrepresentation of community resilience to habitat los

Modelling terrigenous DOC across the north west European Shelf: Fate of riverine input and impact on air-sea CO2 fluxes

Terrigenous carbon in aquatic systems is increasingly recognised as an important part of the global carbon cycle. Despite this, the fate and distribution of terrigenous dissolved organic carbon (tDOC) in coastal and oceanic systems is poorly understood. We have implemented a theoretical framework for the degradation of tDOC across the land to ocean continuum in a 3D hydrodynamical-biogeochemical model on the North West European Shelf. A key feature of this model is that both photochemical and bacterial tDOC degradation rates are age dependant constituting an advance in our ability to describe carbon cycling in the marine environment. Over the time period 1986-2015, 182±17 Gmol yr− 1 of riverine tDOC is input to the shelf. Results indicate that bacterial degradation is by far the most important process in removing tDOC on the shelf, contributing to 73±6 % (132±11 Gmol yr− 1 ) of the total removal flux, while 21±3 % (39±6 Gmol yr− 1 ) of riverine tDOC was advected away from the shelf and photochemical degradation removing 5±0.5 % of the riverine flux. Explicitly including tDOC in the model decreased the air-sea carbon dioxide (CO2) flux by 112±8 Gmol yr− 1 (4±0.4 %), an amount approximately equivalent to the CO2 released by the UK chemical industry in 2020. The reduction is equivalent to 62 % of the riverine tDOC input to the shelf while approximately 17 % of riverine input is incorporated into the foodweb. This work can improve the assumptions of the fate of tDOC by Earth System Models and demonstrates that the inclusion of tDOC in models can impact ecosystem dynamics and change predicted global carbon budgets for the ocean

Identifying sources, pathways and risk drivers in ecosystems of Japanese Encephalitis in an epidemic-prone north Indian district

Japanese Encephalitis (JE) has caused repeated outbreaks in endemic pockets of India. This study was conducted in Kushinagar, a highly endemic district, to understand the human-animal-ecosystem interactions, and the drivers that influence disease transmission. Utilizing the ecosystems approach, a cross-sectional, descriptive study, employing mixed methods design was employed. Four villages (two with pig-rearing and two without) were randomly selected from a high, a medium and a low burden (based on case counts) block of Kushinagar. Children, pigs and vectors were sampled from these villages. A qualitative arm was incorporated to explain the findings from the quantitative surveys. All human serum samples were screened for JE-specific IgM using MAC ELISA and negative samples for JE RNA by rRT-PCR in peripheral blood mononuclear cells. In pigs, IgG ELISA and rRT-PCR for viral RNA were used. Of the 242 children tested, 24 tested positive by either rRT-PCR or MAC ELISA; in pigs, 38 out of the 51 pigs were positive. Of the known vectors, Culex vishnui was most commonly isolated across all biotopes. Analysis of 15 blood meals revealed human blood in 10 samples. Univariable analysis showed that gender, religion, lack of indoor residual spraying of insecticides in the past year, indoor vector density (all species), and not being vaccinated against JE in children were significantly associated with JE positivity. In multivariate analysis, only male gender remained as a significant risk factor. Based on previous estimates of symptomatic: asymptomatic cases of JE, we estimate that there should have been 618 cases from Kushinagar, although only 139 were reported. Vaccination of children and vector control measures emerged as major control activities; they had very poor coverage in the studied villages. In addition, lack of awareness about the cause of JE, lack of faith in the conventional medical healthcare system and multiple referral levels causing delay in diagnosis and treatment emerged as factors likely to result in adverse clinical outcomes

Variations and inter-relationship in outcome from emergency admissions in England: a retrospective analysis of Hospital Episode Statistics from 2005-2010.

BACKGROUND: The quality of care delivered and clinical outcomes of care are of paramount importance. Wide variations in the outcome of emergency care have been suggested, but the scale of variation, and the way in which outcomes are inter-related are poorly defined and are critical to understand how best to improve services. This study quantifies the scale of variation in three outcomes for a contemporary cohort of patients undergoing emergency medical and surgical admissions. The way in which the outcomes of different diagnoses relate to each other is investigated. METHODS: A retrospective study using the English Hospital Episode Statistics 2005-2010 with one-year follow-up for all patients with one of 20 of the commonest and highest-risk emergency medical or surgical conditions. The primary outcome was in-hospital all-cause risk-standardised mortality rate (in-RSMR). Secondary outcomes were 1-year all-cause risk-standardised mortality rate (1 yr-RSMR) and 28-day all-cause emergency readmission rate (RSRR). RESULTS: 2,406,709 adult patients underwent emergency medical or surgical admissions in the groups of interest. Clinically and statistically significant variations in outcome were observed between providers for all three outcomes (p < 0.001). For some diagnoses including heart failure, acute myocardial infarction, stroke and fractured neck of femur, more than 20% of hospitals lay above the upper 95% control limit and were statistical outliers. The risk-standardised outcomes within a given hospital for an individual diagnostic group were significantly associated with the aggregated outcome of the other clinical groups. CONCLUSIONS: Hospital-level risk-standardised outcomes for emergency admissions across a range of specialties vary considerably and cross traditional speciality boundaries. This suggests that global institutional infra-structure and processes of care influence outcomes. The implications are far reaching, both in terms of investigating performance at individual hospitals and in understanding how hospitals can learn from the best performers to improve outcomes

Predation and infanticide influence ideal free choice by a parrot occupying heterogeneous tropical habitats

The ideal free distribution (IFD) predicts that organisms will disperse to sites that maximize their fitness based on availability of resources. Habitat heterogeneity underlies resource variation and influences spatial variation in demography and the distribution of populations. We relate nest site productivity at multiple scales measured over a decade to habitat quality in a box-nesting population of Forpus passerinus (green-rumped parrotlets) in Venezuela to examine critical IFD assumptions. Variation in reproductive success at the local population and neighborhood scales had a much larger influence on productivity (fledglings per nest box per year) than nest site or female identity. Habitat features were reliable cues of nest site quality. Nest sites with less vegetative cover produced greater numbers of fledglings than sites with more cover. However, there was also a competitive cost to nesting in high-quality, low-vegetative cover nest boxes, as these sites experienced the most infanticide events. In the lowland local population, water depth and cover surrounding nest sites were related with F. passerinus productivity. Low vegetative cover and deeper water were associated with lower predation rates, suggesting that predation could be a primary factor driving habitat selection patterns. Parrotlets also demonstrated directional dispersal. Pairs that changed nest sites were more likely to disperse from poor-quality nest sites to high-quality nest sites rather than vice versa, and juveniles were more likely to disperse to, or remain in, the more productive of the two local populations. Parrotlets exhibited three characteristics fundamental to the IFD: habitat heterogeneity within and between local populations, reliable habitat cues to productivity, and active dispersal to sites of higher fitness

Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

Copyright: © 2015 Jetten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedMembership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.This study was supported by 1. Australian Research Council Future Fellowship (FT110100238) awarded to Jolanda Jetten (see http://www.arc.gov.au) 2. Australian Research Council Linkage Grant (LP110200437) to Jolanda Jetten and Genevieve Dingle (see http://www.arc.gov.au) 3. support from the Canadian Institute for Advanced Research Social Interactions, Identity and Well-Being Program to Nyla Branscombe, S. Alexander Haslam, and Catherine Haslam (see http://www.cifar.ca)