67 research outputs found

    Ancient Egypt 1916 Part 4

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    Part 4 of the 1916 Ancient Egypt books. Contents include Sir Gaston Maspero, King Zet (XXIIIrd dynasty), funeral figures, Egyptology in France, origin of polychrome borders, and a cemetery portal.https://knowledge.e.southern.edu/kweeks_coll/1008/thumbnail.jp

    ForestTreeDB: a database dedicated to the mining of tree transcriptomes

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    ForestTreeDB is intended as a resource that centralizes large-scale expressed sequence tag (EST) sequencing results from several tree species (). It currently encompasses 344 878 quality sequences from 68 libraries, from diverse organs of conifer and hybrid poplar trees. It utilizes the Nimbus data model to provide a hosting system for multiple projects, and uses object-relational mapping APIs in Java and Perl for data accesses within an Oracle database designed to be scalable, maintainable and extendable. Transcriptome builds or unigene sets occupy the focal point of the system. Several of the five current species-specific unigenes were used to design microarrays and SNP resources. The ForestTreeDB web application provides the means for multiple combination database queries. It presents the user with a list of discrete queries to retrieve and download large EST datasets or sequences from precompiled unigene assemblies. Functional annotation assignment is not trivial in conifers which are distantly related to angiosperm model plants. Optimal annotations are achieved through database queries that integrate results from several procedures based open-source tools. ForestTreeDB aims to facilitate sequence mining of coherent annotations in multiple species to support comparative genomic approaches. We plan to continuously enrich ForestTreeDB with other resources through collaborations with other genomic projects

    Sprouty2 loss‐induced IL6 drives castration‐resistant prostate cancer through scavenger receptor B1

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    Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal form of treatment‐resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre‐clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self‐sufficient form of CRPC. Mechanistically, HER2‐IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1‐mediated cholesterol uptake in SPRY2‐deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2‐deficient CRPC is dependent on cholesterol bioavailability and SRB1‐mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2‐deficient CRPC

    Neonatal mortality rates, characteristics, and risk factors for neonatal deaths in Ghana:analyses of data from two health and demographic surveillance systems

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    BACKGROUND: Reducing neonatal mortality rates (NMR) in developing countries is a key global health goal, but weak registration systems in the region stifle public health efforts. OBJECTIVE: To calculate NMRs, investigate modifiable risk factors, and explore neonatal deaths by place of birth and death, and cause of death in two administrative areas in Ghana. METHODS: Data on livebirths were extracted from the health and demographic surveillance systems in Navrongo (2004-2012) and Kintampo (2005-2010). Cause of death was determined from neonatal verbal autopsy forms. Univariable and multivariable logistic regression were used to analyse factors associated with neonatal death. Multiple imputations were used to address missing data. RESULTS: The overall NMR was 18.8 in Navrongo (17,016 live births, 320 deaths) and 12.5 in Kintampo (11,207 live births, 140 deaths). The annual NMR declined in both areas. 54.7% of the births occurred in health facilities. 70.9% of deaths occurred in the first week. The main causes of death were infection (NMR 4.3), asphyxia (NMR 3.7) and prematurity (NMR 2.2). The risk of death was higher among hospital births than home births: Navrongo (adjusted OR 1.14, 95% CI: 1.03-1.25, p = 0.01); Kintampo (adjusted OR 1.76, 95% CI: 1.55-2.00, p < 0.01). However, a majority of deaths occurred at home (Navrongo 61.3%; Kintampo 50.7%). Among hospital births dying in hospital, the leading cause of death was asphyxia; among hospital and home births dying at home, it was infection. CONCLUSION: The NMR in these two areas of Ghana reduced over time. Preventing deaths by asphyxia and infection should be prioritised, centred respectively on improving post-delivery care in health facilities and subsequent post-natal care at home

    PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

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    Peroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis

    Generation, annotation, analysis and database integration of 16,500 white spruce EST clusters

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    BACKGROUND: The sequencing and analysis of ESTs is for now the only practical approach for large-scale gene discovery and annotation in conifers because their very large genomes are unlikely to be sequenced in the near future. Our objective was to produce extensive collections of ESTs and cDNA clones to support manufacture of cDNA microarrays and gene discovery in white spruce (Picea glauca [Moench] Voss). RESULTS: We produced 16 cDNA libraries from different tissues and a variety of treatments, and partially sequenced 50,000 cDNA clones. High quality 3' and 5' reads were assembled into 16,578 consensus sequences, 45% of which represented full length inserts. Consensus sequences derived from 5' and 3' reads of the same cDNA clone were linked to define 14,471 transcripts. A large proportion (84%) of the spruce sequences matched a pine sequence, but only 68% of the spruce transcripts had homologs in Arabidopsis or rice. Nearly all the sequences that matched the Populus trichocarpa genome (the only sequenced tree genome) also matched rice or Arabidopsis genomes. We used several sequence similarity search approaches for assignment of putative functions, including blast searches against general and specialized databases (transcription factors, cell wall related proteins), Gene Ontology term assignation and Hidden Markov Model searches against PFAM protein families and domains. In total, 70% of the spruce transcripts displayed matches to proteins of known or unknown function in the Uniref100 database (blastx e-value < 1e-10). We identified multigenic families that appeared larger in spruce than in the Arabidopsis or rice genomes. Detailed analysis of translationally controlled tumour proteins and S-adenosylmethionine synthetase families confirmed a twofold size difference. Sequences and annotations were organized in a dedicated database, SpruceDB. Several search tools were developed to mine the data either based on their occurrence in the cDNA libraries or on functional annotations. CONCLUSION: This report illustrates specific approaches for large-scale gene discovery and annotation in an organism that is very distantly related to any of the fully sequenced genomes. The ArboreaSet sequences and cDNA clones represent a valuable resource for investigations ranging from plant comparative genomics to applied conifer genetics

    Insight into the Architecture of the NuRD Complex: Structure of the RbAp48-MTA1 Subcomplex

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    The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex
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