784 research outputs found

    The Leishmania major BBSome subunit BBS1 is essential for parasite virulence in the mammalian host

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    Bardet–Biedl syndrome (BBS) is a human genetic disorder with a spectrum of symptoms caused by primary cilium dysfunction. The disease is caused by mutations in one of at least 17 identified genes, of which seven encode subunits of the BBSome, a protein complex required for specific trafficking events to and from the primary cilium. The molecular mechanisms associated with BBSome function remain to be fully elucidated. Here, we generated null and complemented mutants of the BBSome subunit BBS1 in the protozoan parasite, Leishmania. In the absence of BBS1, extracellular parasites have no apparent defects in growth, flagellum assembly, motility or differentiation in vitro but there is accumulation of vacuole-like structures close to the flagellar pocket. Infectivity of these parasites for macrophages in vitro is reduced compared with wild-type controls but the null parasites retain the ability to differentiate to the intracellular amastigote stage. However, infectivity of BBS1 null parasites is severely compromised in a BALB/c mouse footpad model. We hypothesize that the absence of BBS1 in Leishmania leads to defects in specific trafficking events that affect parasite persistence in the host. This is the first report of an association between the BBSome complex and pathogen infectivity

    Stillbirth and neonatal death rates across time: the influence of pregnancy terminations and birth defects in a Western Australian population-based cohort study

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    Background: The stillbirth rate in most high income countries reduced in the early part of the 20th century but has apparently been static over the past 2½ decades. However, there has not been any account taken of pregnancy terminations and birth defects on these trends. The current study sought to quantify these relationships using linked Western Australian administrative data for the years 1986–2010. Methods: We analysed a retrospective, population-based cohort of Western Australia births from 1986 to 2010, with de-identified linked data from core population health datasets. Results: The study revealed a significant decrease in the neonatal death rate from 1986 to 2010 (6.1 to 2.1 neonatal deaths per 1000 births; p < .01), while the overall stillbirth rate remained static. The stillbirth trend was driven by deaths in the extremely preterm period (20–27 weeks; which account for about half of all recorded stillbirths and neonatal deaths), masking significant decreases in the rate of stillbirth at very preterm (28–31 weeks), moderate to late preterm (32–36 weeks), and term (37+ weeks). For singletons, birth defects made up an increasing proportion of stillbirths and decreasing proportion of neonatal deaths over the study period—a shift that appears to have been largely driven by the increase in late pregnancy terminations (20 weeks or more gestation). After accounting for pregnancy terminations, we observed a significant downward trend in stillbirth and neonatal death rates at every gestational age. Conclusions: Changes in clinical practice related to pregnancy terminations have played a substantial role in shaping stillbirth and neonatal death rates in Western Australia over the 2½ decades to 2010. The study underscores the need to disaggregate perinatal mortality data in order to support a fuller consideration of the influence of pregnancy terminations and birth defects when assessing change over time in the rates of stillbirth and neonatal death

    An ultrastructural investigation of the surface microbiota present on the leaves and reproductive structures of the resurrection plant Myrothamnus flabellifolia

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    The leaves, flower and stems of the southern African angiosperm resurrection plant Myrothamnus flabellifolia were investigated at the ultrastructural level to determine the source of previously reported fungal contamination. Fungal mycelia and hyphae of the genera Aspergillus and Penicillium were found localized to the hydathodes of the leaves and stigmatic surfaces of the female flowers in both desiccated and hydrated specimens. A waxy bacterium of the genus Bacillus was found to colonise the waxy epidermal surfaces of the leaves and flowers which was also where fungal cells were found to be absent. It is suggested that the wax like deposits within the leaves and stems as well as over the epidermal surface prevent the growth of the fungal organisms. These fungi opportunistically invade moist surfaces, such as the floral stigmas, during periods of moisture availability and may thus negatively impact plant development

    Reconstruction of MIS 5 climate in the central Levant using a stalagmite from Kanaan Cave, Lebanon

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    Lying at the transition between the temperate Mediterranean domain and subtropical deserts, the Levant is a key area to study the palaeoclimatic response over glacial–interglacial cycles. This paper presents a precisely dated last interglacial (MIS 5) stalagmite (129–84 ka) from the Kanaan Cave, Lebanon. Variations in growth rate and isotopic records indicate a warm humid phase at the onset of the last interglacial at ~ 129 ka that lasted until ~ 125 ka. A gradual shift in speleothem isotopic composition (125–122 ka) is driven mainly by the δ18O source effect of the eastern Mediterranean surface waters during sapropel 5 (S5). The onset of glacial inception began after ~ 122 ka, interrupted by a short wet pulse during the sapropel 4 (S4) event. Low growth rates and enriched oxygen and carbon values until ~ 84 ka indicate a transition to drier conditions during Northern Hemisphere glaciation

    Synapse Type-Dependent Expression of Calcium-Permeable AMPA Receptors

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    Calcium-permeable (CP) AMPA-type glutamate receptors (AMPARs) are known to mediate synaptic plasticity in several different interneuron (IN) types. Recent evidence suggests that CP-AMPARs are synapse-specifically expressed at excitatory connections onto a subset of IN types in hippocampus and neocortex. For example, CP-AMPARs are found at connections from pyramidal cells (PCs) to basket cells (BCs), but not to Martinotti cells (MCs). This synapse type-specific expression of CP-AMPARs suggests that synaptic dynamics as well as learning rules are differentially implemented in local circuits and has important implications not just in health but also in disease states such as epilepsy

    Fluctuation Study of the Specific Heat of MgB2

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    The specific heat of polycrystalline Mg11^{11}B2_{2} has been measured with high resolution ac calorimetry from 5 to 45 K at constant magnetic fields. The excess specific heat above Tc_{c} is discussed in terms of Gaussian fluctuations and suggests that Mg11^{11}B2_{2} is a bulk superconductor with Ginzburg-Landau coherence length ξ0=26\xi_{0}=26 \AA . The transition-width broadening in field is treated in terms of lowest-Landau-level (LLL) fluctuations. That analysis requires that ξ0=20\xi_{0}=20 \AA . The underestimate of the coherence length in field, along with deviations from 3D LLL predictions, suggest that there is an influence from the anisotropy of Bc2_{c2} between the c-axis and the a-b plane.Comment: Phys. Rev. B 66, 134515 (2002

    Experimental observation of high field diamagnetic fluctuations in Niobium

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    We have performed a magnetic study of a bulk metallic sample of Nb with critical temperature Tc=8.5T_{c}=8.5 K. Magnetization versus temperature (M {\it vs} T) data obtained for fixed magnetic fields above 1 kOe show a superconducting transition which becomes broader as the field is increased. The data are interpreted in terms of the diamagnetic lowest Landau level (LLL) fluctuation theory. The scaling analysis gives values of the superconducting transition temperature Tc(H)T_{c}(H) consistent with Hc2(T)H_{c2}(T)% . We search for universal 3D LLL behavior by comparing scaling results for Nb and YBaCuO, but obtain no evidence for universality.Comment: 5 pages, 6 figures, Accepted for publication in Phys.Rev.

    Scaling in high-temperature superconductors

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    A Hartree approximation is used to study the interplay of two kinds of scaling which arise in high-temperature superconductors, namely critical-point scaling and that due to the confinement of electron pairs to their lowest Landau level in the presence of an applied magnetic field. In the neighbourhood of the zero-field critical point, thermodynamic functions scale with the scaling variable (TTc2(B))/B1/2ν(T-T_{c2}(B))/B^{1/2\nu}, which differs from the variable (TTc(0))/B1/2ν(T - T_c(0))/B^{1/2\nu} suggested by the gaussian approximation. Lowest-Landau-level (LLL) scaling occurs in a region of high field surrounding the upper critical field line but not in the vicinity of the zero-field transition. For YBaCuO in particular, a field of at least 10 T is needed to observe LLL scaling. These results are consistent with a range of recent experimental measurements of the magnetization, transport properties and, especially, the specific heat of high-TcT_c materials.Comment: 22 pages + 1 figure appended as postscript fil

    Establishing and Prioritising Research Questions for the Treatment of Alopecia Areata: The Alopecia Areata Priority Setting Partnership

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    BACKGROUND: Alopecia areata is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in alopecia areata management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An alopecia areata priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in alopecia areata. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to alopecia areata (and variants) were analyzed. Questions were combined into "indicative uncertainties" following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for alopecia areata to guide researchers and funding bodies to support studies important to both patients and clinicians. This article is protected by copyright. All rights reserved
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