561 research outputs found

    Alliances in the Shadow of Conflict

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    Victorious alliances often fight about the spoils of war. This paper presents an experiment on the determinants of whether alliances break up and fight internally after having defeated a joint enemy. First, if peaceful sharing yields an asymmetric rent distribution, this increases the likelihood of fighting. In turn, anticipation of the higher likelihood of internal fight reduces the alliance’s ability to succeed against the outside enemy. Second, the option to make non-binding declarations on non-aggression in the relationship between alliance members does not make peaceful settlement within the alliance more likely. Third, higher differences in the alliance players’ contributions to alliance effort lead to more internal conflict and more intense fighting

    Rab3D is critical for secretory granule maturation in PC12 cells.

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    Neuropeptide- and hormone-containing secretory granules (SGs) are synthesized at the trans-Golgi network (TGN) as immature secretory granules (ISGs) and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs). Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I) decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs

    A generic method for estimating and smoothing multispecies biodiversity indices using intermittent data

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    Biodiversity indicators summarise extensive, complex ecological data sets and are important in influencing government policy. Component data consist of time-varying indices for each of a number of different species. However, current biodiversity indicators suffer from multiple statistical shortcomings. We describe a state-space formulation for new multispecies biodiversity indicators, based on rates of change in the abundance or occupancy probability of the contributing individual species. The formulation is flexible and applicable to different taxa. It possesses several advantages, including the ability to accommodate the sporadic unavailability of data, incorporate variation in the estimation precision of the individual species’ indices when appropriate, and allow the direct incorporation of smoothing over time. Furthermore, model fitting is straightforward in Bayesian and classical implementations, the latter adopting either efficient Hidden Markov modelling or the Kalman filter. Conveniently, the same algorithms can be adopted for cases based on abundance or occupancy data—only the subsequent interpretation differs. The procedure removes the need for bootstrapping which can be prohibitive. We recommend which of two alternatives to use when taxa are fully or partially sampled. The performance of the new approach is demonstrated on simulated data, and through application to three diverse national UK data sets on butterflies, bats and dragonflies. We see that uncritical incorporation of index standard errors should be avoided

    Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1

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    Disruptions in axonal transport have been implicated in a wide range of neurodegenerative diseases. Cramping 1 (Cra1/+) and Legs at odd angles (Loa/+) mice, with hypomorphic mutations in the dynein heavy chain 1 gene, which encodes the ATPase of the retrograde motor protein dynein, were originally reported to exhibit late onset motor neuron disease. Subsequent, conflicting reports suggested that sensory neuron disease without motor neuron loss underlies the phenotypes of Cra1/+ and Loa/+ mice. Here, we present behavioral and anatomical analyses of Cra1/+ mice. We demonstrate that Cra1/+ mice exhibit early onset, stable behavioral deficits, including abnormal hindlimb posturing and decreased grip strength. These deficits do not progress through 24 months of age. No significant loss of primary motor neurons or dorsal root ganglia sensory neurons was observed at ages where the mice exhibited clear symptomatology. Instead, there is a decrease in complexity of neuromuscular junctions. These results indicate that disruption of dynein function in Cra1/+ mice results in abnormal morphology of neuromuscular junctions. The time course of behavioral deficits, as well as the nature of the morphological defects in neuromuscular junctions, suggests that disruption of dynein function in Cra1/+ mice causes a developmental defect in synapse assembly or stabilization

    Molecular analysis of the Acinetobacter baumannii biofilm-associated protein

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    Acinetobacter baumannii is a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability of A. baumannii to survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of the A. baumannii biofilm-associated protein (Bap) in 24 carbapenem-resistant A. baumannii ST92 strains isolated from a single institution over a 10-year period. The bap gene was highly prevalent, with 22/24 strains being positive for bap by PCR. Partial sequencing of bap was performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that Bap(MS1968) clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, the bap(MS1968) gene was cloned, and its expression in a recombinant Escherichia coli strain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority of A. baumannii strains expressed an similar to 200-kDa Bap protein. Further analysis of three Bap-positive A. baumannii strains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth by A. baumannii clinical isolates

    Proteomic profiling of neuronal mitochondria reveals modulators of synaptic architecture

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    Abstract Background Neurons are highly polarized cells consisting of three distinct functional domains: the cell body (and associated dendrites), the axon and the synapse. Previously, it was believed that the clinical phenotypes of neurodegenerative diseases were caused by the loss of entire neurons, however it has recently become apparent that these neuronal sub-compartments can degenerate independently, with synapses being particularly vulnerable to a broad range of stimuli. Whilst the properties governing the differential degenerative mechanisms remain unknown, mitochondria consistently appear in the literature, suggesting these somewhat promiscuous organelles may play a role in affecting synaptic stability. Synaptic and non-synaptic mitochondrial subpools are known to have different enzymatic properties (first demonstrated by Lai et al., 1977). However, the molecular basis underpinning these alterations, and their effects on morphology, has not been well documented. Methods The current study has employed electron microscopy, label-free proteomics and in silico analyses to characterize the morphological and biochemical properties of discrete sub-populations of mitochondria. The physiological relevance of these findings was confirmed in-vivo using a molecular genetic approach at the Drosophila neuromuscular junction. Results Here, we demonstrate that mitochondria at the synaptic terminal are indeed morphologically different to non-synaptic mitochondria, in both rodents and human patients. Furthermore, generation of proteomic profiles reveals distinct molecular fingerprints – highlighting that the properties of complex I may represent an important specialisation of synaptic mitochondria. Evidence also suggests that at least 30% of the mitochondrial enzymatic activity differences previously reported can be accounted for by protein abundance. Finally, we demonstrate that the molecular differences between discrete mitochondrial sub-populations are capable of selectively influencing synaptic morphology in-vivo. We offer several novel mitochondrial candidates that have the propensity to significantly alter the synaptic architecture in-vivo. Conclusions Our study demonstrates discrete proteomic profiles exist dependent upon mitochondrial subcellular localization and selective alteration of intrinsic mitochondrial proteins alters synaptic morphology in-vivo

    Aflatoxin exposure in pregnant women of mixed status of human immunodeficiency virus infection and rate of gestational weight gain: a Ugandan cohort study

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    OBJECTIVES: To examine the association between aflatoxin (AF) exposure during pregnancy and rate of gestational weight gain (GWG) in a sample of pregnant women of mixed HIV status in Gulu, northern Uganda. METHODS: 403 pregnant women were included (133 HIV‐infected on antiretroviral therapy (ART), 270 HIV‐uninfected). Women’s weight, height and socio‐demographic characteristics were collected at baseline (~19 weeks’ gestation); weight was assessed at each follow‐up visit. Serum was collected at baseline and tested for aflatoxin B1‐lysine adduct (AFB‐lys) levels using high‐performance liquid chromatography (HPLC). Linear mixed‐effects models were used to examine the association between AFB‐lys levels and rate of GWG. RESULTS: AFB‐lys levels (detected in 98.3% of samples) were higher among HIV‐infected pregnant women than HIV‐uninfected pregnant women [median (interquartile range): 4.8 (2.0, 15.0) vs. 3.5 (1.6, 6.1) pg/mg of albumin, P < 0.0001]. Adjusting for HIV status, a one‐log increase in aflatoxin levels was associated with a 16.2 g per week lower rate of GWG (P = 0.028). The association between AFB‐lys and the rate of GWG was stronger and significant only among HIV‐infected women on ART [−25.7 g per week per log (AFB‐lys), P = 0.009 for HIV‐infected women vs. −7.5 g per week per log (AFB‐lys), P = 0.422 for HIV‐uninfected women]. CONCLUSIONS: Pregnant women with higher levels of AF exposure had lower rates of GWG. The association was stronger for HIV‐infected women on ART, suggesting increased risk.https://onlinelibrary.wiley.com/doi/10.1111/tmi.13457Published versio

    Analyst Optimism and Incentives under Market Uncertainty

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    We examine how analysts’ changing incentives driven by changes in market uncertainty affect their forecast optimism. Analysts issue more optimistically biased earnings forecasts and buy recommendations under high market uncertainty (VIX). The lower reputational costs and larger benefits of optimistic output explain the increased optimistic output: Analysts are less likely to be penalized for inaccuracy and can stimulate more trading activity from optimistically biased output when market uncertainty is high. We find that the likelihood of analysts’ turnover decreases, while the trading volume associated with optimistic output increases, with VIX. No evidence suggests that analysts’ self‐selection affects our findings on optimism and market uncertainty.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137733/1/fire12138.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137733/2/fire12138_am.pd

    Measurement of ψ(2S)\psi(2S) decays to baryon pairs

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    A sample of 3.95M ψ(2S)\psi(2S) decays registered in the BES detector are used to study final states containing pairs of octet and decuplet baryons. We report branching fractions for ψ(2S)ppˉ\psi(2S)\to p\bar{p}, ΛΛˉ\Lambda\bar{\Lambda}, Σ0Σˉ0\Sigma^0\bar{\Sigma}{}^0, ΞΞˉ+\Xi^-\bar{\Xi}{}^+, Δ++Δˉ\Delta^{++}\bar{\Delta}{}^{--}, Σ+(1385)Σˉ(1385)\Sigma^+(1385)\bar{\Sigma}{}^-(1385), Ξ0(1530)Ξˉ0(1530)\Xi^0(1530)\bar{\Xi}{}^0(1530), and ΩΩˉ+\Omega^-\bar{\Omega}{}^+. These results are compared to expectations based on the SU(3)-flavor symmetry, factorization, and perturbative QCD.Comment: 22 pages, 21 figures, 4 table

    “When I Was Circumcised I Was Taught Certain Things”: Risk Compensation and Protective Sexual Behavior among Circumcised Men in Kisumu, Kenya

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    Background: Male circumcision has been shown to reduce the transmission of HIV from women to men through vaginal sex by approximately 60%. There is concern that men may engage in risk compensation after becoming circumcised, diminishing the benefits of male circumcision. Methods and Findings: We conducted qualitative interviews with 30 sexually active circumcised men in Kisumu, Kenya from March to November 2008. Most respondents reported no behavior change or increasing protective sexual behaviors including increasing condom use and reducing the number of sexual partners. A minority of men reported engaging in higher risk behaviors either not using condoms or increasing the number of sex partners. Circumcised respondents described being able to perform more rounds of sex, easier condom use, and fewer cuts on the penis during sex. Conclusions: Results illustrate that information about MC’s protection against HIV has disseminated into the larger community and MC accompanied by counseling and HIV testing can foster positive behavior change and maintain sexua
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