441 research outputs found

    The Conduct of War 1789-1961

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    Upper limb activity over time in complex regional pain syndrome type 1 as objectively measured with an upper limb-activity monitor: an explorative multiple case study.

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    BACKGROUND: An upper limb-activity monitor (ULAM) has been developed to determine activity limitations in complex regional pain syndrome type 1 (CRPS1). The ULAM is based on 24h ambulatory monitoring of body segment accelerations and enables valid and objective quantification of mobility and upper limb activity in transversal studies. AIMS: To explore upper limb activity over time in acute upper limb CRPS1 a

    Pannexin 1 regulates adipose stromal cell differentiation and fat accumulation

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    Pannexin 1 (Panx1) is a channel-forming glycoprotein important in paracrine signaling and cellular development. In this study, we discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain and blood markers of obesity as compared to WT controls, except for an increase in glucose and insulin levels. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high-fat diet. To uncover the cellular mechanism responsible for the increased fat content in the KO, we isolated primary cultures of adipose-derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. We concluded that Panx1 plays a key role in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo

    Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer

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    In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal therapy naïve primary breast carcinomas was immunohistochemically (IHC) stained for PSAT1. Staining was analyzed for association with patient's time to progression (TTP) and overall response on first-line tamoxifen for recurrent disease. PSAT1 mRNA levels were also assessed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR; n = 161) and Affymetrix GeneChip (n = 155). Association of PSAT1 to biological pathways on tamoxifen outcome were assessed by global test. PSAT1 protein and mRNA levels were significantly associated to poor outcome to tamoxifen treatment. When comparing PSAT1

    Consistently high incidence of Wolbachia in global fig wasp communities

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    1. Wolbachia are very common and widespread endosymbionts of arthropods. They can have a considerable effect on their host's fitness. It has been estimated that as many as 40% of arthropod species are infected with Wolbachia, but particular taxonomic groups and ecological niches display significantly higher or lower incidences. 2. In this study, we combine an African sample with those of three previous studies from three other continents. We reanalyzed Wolbachia incidence in 172 fig wasp species (including pollinators, non pollinators, gallers and non gallers) associated with 81 fig trees of six subgenera, and estimated that > 80% of fig wasp species are infected with Wolbachia, which is far higher than putative global infection rates in arthropods. 3. We found that, within fig wasps, incidence does not vary consistently with respect to host taxonomy, ecology or geography. In particular, incidence seems remarkably constant across samples from different geographical locations.University of Pretoriahttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2311hb201

    Energy, interaction, and photoluminescence of spin-reversed quasielectrons in fractional quantum Hall systems

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    The energy and photoluminescence spectra of a two-dimensional electron gas in the fractional quantum Hall regime are studied. The single-particle properties of reversed-spin quasielectrons (QER_{\rm R}'s) as well as the pseudopotentials of their interaction with one another and with Laughlin quasielectrons (QE's) and quasiholes (QH's) are calculated. Based on the short-range character of the QER_{\rm R}--QER_{\rm R} and QER_{\rm R}--QE repulsion, the partially unpolarized incompressible states at the filling factors ν=411\nu={4\over11} and 513{5\over13} are postulated within Haldane's hierarchy scheme. To describe photoluminescence, the family of bound h(h(QER)n_{\rm R})_n states of a valence hole hh and nn QER_{\rm R}'s are predicted in analogy to the found earlier fractionally charged excitons hhQEn_n. The binding energy and optical selection rules for both families are compared. The hhQER_{\rm R} is found radiative in contrast to the dark hhQE, and the h(h(QER)2_{\rm R})_2 is found non-radiative in contrast to the bright hhQE2_2.Comment: 9 pages, 6 figure

    Spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury in skeletally mature rats

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    Objective: Characterise the spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury (SCI) in the skeletally mature rat in the acute (4-week) period following injury. Methods: The spinal cord of 5-month old male rats was transected at the T9 level. Outcome measures were assessed using micro-computed tomography, three-point bending and serum markers at 1-, 2-, and 4-weeks post-transection. Comparison was made with time-0 and sham animals. Results: Lower levels of circulating serum bone formation markers and higher bone resorption markers suggested uncoupled bone turnover as early at 1-week post-transection. Micro-computed tomography showed metaphyseal and epiphyseal trabecular bone loss was observed only at 4-weeks post-transection. The bone loss was site-specific with a more severe reduction in trabecular BV/TV observed in the metaphyseal (50%) relative to epiphyseal (19%) region. Metaphyseal trabecular bone exhibited a 110% reduction in connectivity density while the epiphyseal trabecular bone was unaffected. Cortical bone deficits were not seen over the time periods examined. Conclusions: The study demonstrates that the skeletally mature spinal cord transected rat model replicates the biphasic pattern of osteoporotic changes observed in the human SCI population, providing a relevant model for testing the efficacy of interventions against SCI-induced osteoporosis

    4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer

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    Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi-center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker

    Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

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    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules
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