202 research outputs found

    Whole carcass diets: a role for fibre in gastrointestinal health of cheetahs?

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    This study was undertaken to test the hypothesis that altered podocyte slit protein nephrin distribution is associated with disturbed polarity protein expressions in podocytes from preeclampsia (PE). We examined expressions and distributions of nephrin, podoplanin, polarity protein partitioning defective-3 (PARD-3), and PARD-6 in podocytes from PE. Podocyte cell line (AB 8/13 cells) was used as control. Podocytes were found in all severe PE cases. In contrast, no podocyte was found in the samples from normal pregnancies and mild PE. Compared to control cells, nephrin, PARD-3 and PARD-6 expressions were reduced or lost in podocytes from severe PE. Podoplanin was expressed in podocyte surface membrane on control cells but reduced in podocytes from PE. These findings indicate that loss of slit protein nephrin and polarity protein PARD-3 and PARD-6 on foot processes could explain for podocyte detachment from glomerular basement membrane and lead to podocyte shedding in PE. © The Author(s) 2011.link_to_subscribed_fulltex

    Trauma Care in Older People: charting a path from outlier to excellence

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    Trauma in older people leads to substantial morbidity and mortality. The National Hip Fracture Database (NHFD) has driven improved practice with units compared to identify outliers. In 2013, our unit was an outlier for mortality post hip fracture (30-day mortality 12.2% vs. 8.3% nationally). This triggered external review. In 2019 the unit was highlighted as an exemplar in the UK. We describe the process that moved us from outlier to outstanding. After the initial review process, we made changes to our healthcare system, with regular reassessment of progress and care quality. Examples include a dedicated hip fracture unit, strong leadership (Nursing, Orthopaedic, Geriatrician, Anaesthetic), consultant-led in-depth monthly mortality reviews, changes to admission pathways and delirium prevention. Improvements were seen in all aspects of hip fracture care in 2019 compared with 2012. Thirty-day case-mixed adjusted mortality halved (12.2–6.1%), with substantial reductions in reoperations and pressure sores. Length of stay reduced by 5.9 days. In 2019 our unit’s performance was significantly above the national average for all six indicators assessed by NHFD: prompt orthogeriatric review (97% vs. 91% national average), prompt surgery (85% vs. 68%); NICE compliant surgery (85% vs. 74%); prompt mobilisation (93% vs. 81%); not delirious postoperatively (77% vs. 69%); return to original residence (78% vs. 71%). The NHFD highlighted our Unit as one of nine (from 175 total) highly performing UK trusts. We summarise our service development and improvement work undertaken to achieve ‘outstanding’ status, which provides a valuable template to units managing trauma in older people

    Knowledge production in humanitarian crises: beware of the innovation trap.

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    Correspondence - No abstract available

    Lunar basalt chronology, mantle differentiation and implications for determining the age of the Moon

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    Despite more than 40 years of studying Apollo samples, the age and early evolution of the Moon remain contentious. Following the formation of the Moon in the aftermath of a giant impact, the resulting Lunar Magma Ocean (LMO) is predicted to have generated major geochemically distinct silicate reservoirs, including the sources of lunar basalts. Samples of these basalts, therefore, provide a unique opportunity to characterize these reservoirs. However, the precise timing and extent of geochemical fractionation is poorly constrained, not least due to the difficulty in determining accurate ages and initial Pb isotopic compositions of lunar basalts. Application of an in situ ion microprobe approach to Pb isotope analysis has allowed us to obtain precise crystallization ages from six lunar basalts, typically with an uncertainty of about ±10Ma, as well as constrain their initial Pb-isotopic compositions. This has enabled construction of a two-stage model for the Pb-isotopic evolution of lunar silicate reservoirs, which necessitates the prolonged existence of high-μ reservoirs in order to explain the very radiogenic compositions of the samples. Further, once firm constraints on U and Pb partitioning behaviour are established, this model has the potential to help distinguish between conflicting estimates for the age of the Moon. Nonetheless, we are able to constrain the timing of a lunar mantle reservoir differentiation event at 4376±18Ma, which is consistent with that derived from the Sm–Nd and Lu–Hf isotopic systems, and is interpreted as an average estimate of the time at which the high-μ urKREEP reservoir was established and the Ferroan Anorthosite (FAN) suite was formed

    Phylogeographic analysis reveals association of tick-borne pathogen, Anaplasma marginale, MSP1a sequences with ecological traits affecting tick vector performance

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    <p>Abstract</p> <p>Background</p> <p>The tick-borne pathogen <it>Anaplasma marginale</it>, which is endemic worldwide, is the type species of the genus <it>Anaplasma </it>(Rickettsiales: Anaplasmataceae). <it>Rhipicephalus </it>(<it>Boophilus</it>) <it>microplus </it>is the most important tick vector of <it>A. marginale </it>in tropical and subtropical regions of the world. Despite extensive characterization of the genetic diversity in <it>A. marginale </it>geographic strains using major surface protein sequences, little is known about the biogeography and evolution of <it>A. marginale </it>and other <it>Anaplasma </it>species. For <it>A. marginale</it>, MSP1a was shown to be involved in vector-pathogen and host-pathogen interactions and to have evolved under positive selection pressure. The MSP1a of <it>A. marginale </it>strains differs in molecular weight because of a variable number of tandem 23-31 amino acid repeats and has proven to be a stable marker of strain identity. While phylogenetic studies of MSP1a repeat sequences have shown evidence of <it>A. marginale</it>-tick co-evolution, these studies have not provided phylogeographic information on a global scale because of the high level of MSP1a genetic diversity among geographic strains.</p> <p>Results</p> <p>In this study we showed that the phylogeography of <it>A. marginale </it>MSP1a sequences is associated with world ecological regions (ecoregions) resulting in different evolutionary pressures and thence MSP1a sequences. The results demonstrated that the MSP1a first (R1) and last (RL) repeats and microsatellite sequences were associated with world ecoregion clusters with specific and different environmental envelopes. The evolution of R1 repeat sequences was found to be under positive selection. It is hypothesized that the driving environmental factors regulating tick populations could act on the selection of different <it>A. marginale </it>MSP1a sequence lineages, associated to each ecoregion.</p> <p>Conclusion</p> <p>The results reported herein provided the first evidence that the evolution of <it>A. marginale </it>was linked to ecological traits affecting tick vector performance. These results suggested that some <it>A. marginale </it>strains have evolved under conditions that support pathogen biological transmission by <it>R. microplus</it>, under different ecological traits which affect performance of <it>R. microplus </it>populations. The evolution of other <it>A. marginale </it>strains may be linked to transmission by other tick species or to mechanical transmission in regions where <it>R. microplus </it>is currently eradicated. The information derived from this study is fundamental toward understanding the evolution of other vector-borne pathogens.</p

    Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

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    In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease
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