Prevalence and Correlates of Common Mental Disorders among Mothers of Young Children in Kilimanjaro Region of Tanzania.

Although poor maternal mental health is a major public health problem, with detrimental effects on the individual, her children and society, information on its correlates in low-income countries is sparse. This study investigates the prevalence of common mental disorders (CMD) among at-risk mothers, and explores its associations with sociodemographic factors. This population-based survey of mothers of children aged 0-36 months used the 14-item Shona Symptom Questionnaire (SSQ). Mothers whose response was "yes" to 8 or more items on the scale were defined as "at risk of CMD." Of the 1,922 mothers (15-48 years), 28.8% were at risk of CMD. Risk of CMD was associated with verbal abuse, physical abuse, a partner who did not help with the care of the child, being in a polygamous relationship, a partner with low levels of education, and a partner who smoked cigarettes. Cohabiting appeared to be protective. Taken together, our results indicate the significance of the quality of relations with one's partner in shaping maternal mental health. The high proportion of mothers who are at risk of CMD emphasizes the importance of developing evidence-based mental health programmes as part of the care package aimed at improving maternal well-being in Tanzania and other similar settings

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Obscured phylogeny and possible recombinational dormancy in Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>is one of the best studied organisms in all of biology, but its phylogenetic structure has been difficult to resolve with current data and analytical techniques. We analyzed single nucleotide polymorphisms in chromosomes of representative strains to reconstruct the topology of its emergence.</p> <p>Results</p> <p>The phylogeny of <it>E. coli </it>varies according to the segment of chromosome analyzed. Recombination between extant <it>E. coli </it>groups is largely limited to only three intergroup pairings.</p> <p>Conclusions</p> <p>Segment-dependent phylogenies most likely are legacies of a complex recombination history. However, <it>E. coli </it>are now in an epoch in which they no longer broadly share DNA. Using the definition of species as organisms that freely exchange genetic material, this recombinational dormancy could reflect either the end of <it>E. coli </it>as a species, or herald the coalescence of <it>E. coli </it>groups into new species.</p

Overexpression of Nrdp1 in the Heart Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice

BACKGROUND: Cardiac cell death and generation of oxidative stress contribute to doxorubicin (DOX)-induced cardiac dysfunction. E3 ligase Nrdp1 plays a critical role in the regulation of cell apoptosis, inflammation and production of reactive oxygen species (ROS), which may contribute to heart failure. However, the role of Nrdp1 in DOX-induced cardiac injury remains to be determined. METHODS AND RESULTS: We examined the effect of Nrdp1 overexpression with DOX treatment in rat neonatal cardiomyocytes and mouse heart tissue. Cardiomyocytes were infected with adenovirus containing GFP (Ad-GFP), Nrdp1 wild-type (Ad-Nrdp1) or the dominant-negative form of Nrdp1 (Ad-Dn-Nrdp1), then treated with DOX for 24 hr. DOX treatment increased cell death and apoptosis, with Ad-Nrdp1 infection enhancing these actions but Ad-Dn-Nrdp1 infection attenuating these effects. Furthermore, 5 days after a single injection of DOX (20 mg/kg, intraperitoneally), Nrdp1 transgenic mice (TG) showed decreased cardiac function and increased apoptosis, autophagy and oxidative stress as compared with wild-type (WT) mice (P<0.01). Survival rate was significantly lower in Nrdp1 TG mice than in WT mice 10 days after DOX injection (P<0.01). CONCLUSIONS/SIGNIFICANCE: These results were associated with decreased activation of Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. Nrdp1 may be a key mediator in the development of cardiac dysfunction after DOX treatment and associated with inhibition of Akt, ERK1/2 and STAT3. Nrdp1 may be a new therapeutic target in protecting against the cardiotoxic effects of DOX

Mutation of a Single Residue Renders Human Tetherin Resistant to HIV-1 Vpu-Mediated Depletion

The recently identified restriction factor tetherin/BST-2/CD317 is an interferon-inducible trans-membrane protein that restricts HIV-1 particle release in the absence of the HIV-1 countermeasure viral protein U (Vpu). It is known that Tantalus monkey CV1 cells can be rendered non-permissive to HIV-1 release upon stimulation with type 1 interferon, despite the presence of Vpu, suggesting species-specific sensitivity of tetherin proteins to viral countermeasures such as Vpu. Here we demonstrate that Tantalus monkey tetherin restricts HIV-1 by nearly two orders of magnitude, but in contrast to human tetherin the Tantalus protein is insensitive to HIV-1 Vpu. We have investigated tetherin's sensitivity to Vpu using positive selection analyses, seeking evidence for evolutionary conflict between tetherin and viral countermeasures. We provide evidence that tetherin has undergone positive selection during primate evolution. Mutation of a single amino acid (showing evidence of positive selection) in the trans-membrane cap of human tetherin to that in Tantalus monkey (T45I) substantially impacts on sensitivity to HIV-1 Vpu, but not on antiviral activity. Finally, we provide evidence that cellular steady state levels of tetherin are substantially reduced by Vpu, and that the T45I mutation abrogates this effect. This study provides evidence that tetherin is important in protecting mammals against viral infection, and that the HIV-1 Vpu–mediated countermeasure is specifically adapted to act against human tetherin. It also emphasizes the power of selection analyses to illuminate the molecular details of host–virus interactions. This work suggests that tetherin binding agents might protect it from viral encoded countermeasures and thus make powerful antivirals

Ancient and Recent Adaptive Evolution of Primate Non-Homologous End Joining Genes

In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS) test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes

Echinacea purpurea and osteopathic manipulative treatment in children with recurrent otitis media: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Recurrent otitis media is a common problem in young children. Echinacea and osteopathic manipulative treatment have been proposed as preventive measures, but have been inadequately studied. This study was designed to assess the efficacy of <it>Echinacea purpurea </it>and/or osteopathic manipulative treatment (OMT) for prevention of acute otitis media in otitis-prone children.</p> <p>Methods</p> <p>A randomized, placebo-controlled, two-by-two factorial trial with 6-month follow-up, conducted 1999 – 2002 in Tucson, Arizona. Patients were aged 12–60 months with recurrent otitis media, defined as three or more separate episodes of acute otitis media within six months, or at least four episodes in one year. Ninety children (44% white non-Hispanic, 39% Hispanic, 57% male) were enrolled, of which 84 had follow-up for at least 3 months. Children were randomly assigned to one of four protocol groups: double placebo, echinacea plus sham OMT, true OMT (including cranial manipulation) plus placebo echinacea, or true echinacea plus OMT. An alcohol extract of <it>Echinacea purpurea </it>roots and seeds (or placebo) was administered for 10 days at the first sign of each common cold. Five OMT visits (or sham treatments) were offered over 3 months.</p> <p>Results</p> <p>No interaction was found between echinacea and OMT. Echinacea was associated with a borderline increased risk of having at least one episode of acute otitis media during 6-month follow-up compared to placebo (65% versus 41%; relative risk, 1.59, 95% CI 1.04, 2.42). OMT did not significantly affect risk compared to sham (44% versus 61%; relative risk, 0.72, 95% CI 0.48, 1.10).</p> <p>Conclusion</p> <p>In otitis-prone young children, treating colds with this form of echinacea does not decrease the risk of acute otitis media, and may in fact increase risk. A regimen of up to five osteopathic manipulative treatments does not significantly decrease the risk of acute otitis media.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00010465</p

Molecular evolution of the vertebrate TLR1 gene family - a complex history of gene duplication, gene conversion, positive selection and co-evolution

<p>Abstract</p> <p>Background</p> <p>The Toll-like receptors represent a large superfamily of type I transmembrane glycoproteins, some common to a wide range of species and others are more restricted in their distribution. Most members of the Toll-like receptor superfamily have few paralogues; the exception is the TLR1 gene family with four closely related genes in mammals TLR1, TLR2, TLR6 and TLR10, and four in birds TLR1A, TLR1B, TLR2A and TLR2B. These genes were previously thought to have arisen by a series of independent gene duplications. To understand the evolutionary pattern of the TLR1 gene family in vertebrates further, we cloned the sequences of TLR1A, TLR1B, TLR2A and TLR2B in duck and turkey, constructed phylogenetic trees, predicted codons under positive selection and identified co-evolutionary amino acid pairs within the TLR1 gene family using sequences from 4 birds, 28 mammals, an amphibian and a fish.</p> <p>Results</p> <p>This detailed phylogenetic analysis not only clarifies the gene gains and losses within the TLR1 gene family of birds and mammals, but also defines orthologues between these vertebrates. In mammals, we predict amino acid sites under positive selection in TLR1, TLR2 and TLR6 but not TLR10. We detect co-evolution between amino acid residues in TLR2 and the other members of this gene family predicted to maintain their ability to form functional heterodimers. In birds, we predict positive selection in the TLR2A and TLR2B genes at functionally significant amino acid residues. We demonstrate that the TLR1 gene family has mostly been subject to purifying selection but has also responded to directional selection at a few sites, possibly in response to pathogen challenge.</p> <p>Conclusions</p> <p>Our phylogenetic and structural analyses of the vertebrate TLR1 family have clarified their evolutionary origins and predict amino acid residues likely to be important in the host's defense against invading pathogens.</p

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV