674 research outputs found

    White Fat Progenitor Cells Reside in the Adipose Vasculature

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    White adipose (fat) tissues regulate metabolism, reproduction, and life span. Adipocytes form throughout life, with the most marked expansion of the lineage occurring during the postnatal period. Adipocytes develop in coordination with the vasculature, but the identity and location of white adipocyte progenitor cells in vivo are unknown. We used genetically marked mice to isolate proliferating and renewing adipogenic progenitors. We found that most adipocytes descend from a pool of these proliferating progenitors that are already committed, either prenatally or early in postnatal life. These progenitors reside in the mural cell compartment of the adipose vasculature, but not in the vasculature of other tissues. Thus, the adipose vasculature appears to function as a progenitor niche and may provide signals for adipocyte development

    Genome Stability Is in the Eye of the Beholder: CR1 Retrotransposon Activity Varies Significantly across Avian Diversity

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    Since the sequencing of the zebra finch genome it has become clear that avian genomes, while largely stable in terms of chromosome number and gene synteny, are more dynamic at an intrachromosomal level. A multitude of intrachromosomal rearrangements and significant variation in transposable element (TE) content have been noted across the avian tree. TEs are a source of genome plasticity, because their high similarity enables chromosomal rearrangements through nonallelic homologous recombination, and they have potential for exaptation as regulatory and coding sequences. Previous studies have investigated the activity of the dominant TE in birds, chicken repeat 1 (CR1) retrotransposons, either focusing on their expansion within single orders, or comparing passerines with nonpasserines. Here, we comprehensively investigate and compare the activity of CR1 expansion across orders of birds, finding levels of CR1 activity vary significantly both between and within orders. We describe high levels of TE expansion in genera which have speciated in the last 10 Myr including kiwis, geese, and Amazon parrots; low levels of TE expansion in songbirds across their diversification, and near inactivity of TEs in the cassowary and emu for millions of years. CR1s have remained active over long periods of time across most orders of neognaths, with activity at any one time dominated by one or two families of CR1s. Our findings of higher TE activity in species-rich clades and dominant families of TEs within lineages mirror past findings in mammals and indicate that genome evolution in amniotes relies on universal TE-driven processes

    Integral and peripheral association of proteins and protein complexes with Yersinia pestis inner and outer membranes

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    Yersinia pestis proteins were sequentially extracted from crude membranes with a high salt buffer (2.5 M NaBr), an alkaline solution (180 mM Na2CO3, pH 11.3) and membrane denaturants (8 M urea, 2 M thiourea and 1% amidosulfobetaine-14). Separation of proteins by 2D gel electrophoresis was followed by identification of more than 600 gene products by MS. Data from differential 2D gel display experiments, comparing protein abundances in cytoplasmic, periplasmic and all three membrane fractions, were used to assign proteins found in the membrane fractions to three protein categories: (i) integral membrane proteins and peripheral membrane proteins with low solubility in aqueous solutions (220 entries); (ii) peripheral membrane proteins with moderate to high solubility in aqueous solutions (127 entries); (iii) cytoplasmic or ribosomal membrane-contaminating proteins (80 entries). Thirty-one proteins were experimentally associated with the outer membrane (OM). Circa 50 proteins thought to be part of membrane-localized, multi-subunit complexes were identified in high Mr fractions of membrane extracts via size exclusion chromatography. This data supported biologically meaningful assignments of many proteins to the membrane periphery. Since only 32 inner membrane (IM) proteins with two or more predicted transmembrane domains (TMDs) were profiled in 2D gels, we resorted to a proteomic analysis by 2D-LC-MS/MS. Ninety-four additional IM proteins with two or more TMDs were identified. The total number of proteins associated with Y. pestis membranes increased to 456 and included representatives of all six β-barrel OM protein families and 25 distinct IM transporter families

    Development stage-specific proteomic profiling uncovers small, lineage specific proteins most abundant in the Aspergillus Fumigatus conidial proteome

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    Background The pathogenic mold Aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. Germination of inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process. Results To gain insights into early germination events and facilitate the identification of potential stage-specific biomarkers and vaccine candidates, we have used quantitative shotgun proteomics to elucidate patterns of protein abundance changes during early fungal development. Four different stages were examined: dormant conidia, isotropically expanding conidia, hyphae in which germ tube emergence has just begun, and pre-septation hyphae. To enrich for glycan-linked cell wall proteins we used an alkaline cell extraction method. Shotgun proteomic resulted in the identification of 375 unique gene products with high confidence, with no evidence for enrichment of cell wall-immobilized and secreted proteins. The most interesting discovery was the identification of 52 proteins enriched in dormant conidia including 28 proteins that have never been detected in the A. fumigatus conidial proteome such as signaling protein Pil1, chaperones BipA and calnexin, and transcription factor HapB. Additionally we found many small, Aspergillus specific proteins of unknown function including 17 hypothetical proteins. Thus, the most abundant protein, Grg1 (AFUA_5G14210), was also one of the smallest proteins detected in this study (M.W. 7,367). Among previously characterized proteins were melanin pigment and pseurotin A biosynthesis enzymes, histones H3 and H4.1, and other proteins involved in conidiation and response to oxidative or hypoxic stress. In contrast, expanding conidia, hyphae with early germ tubes, and pre-septation hyphae samples were enriched for proteins responsible for housekeeping functions, particularly translation, respiratory metabolism, amino acid and carbohydrate biosynthesis, and the tricarboxylic acid cycle. Conclusions The observed temporal expression patterns suggest that the A. fumigatus conidia are dominated by small, lineage-specific proteins. Some of them may play key roles in host-pathogen interactions, signal transduction during conidial germination, or survival in hostile environments

    Epidemiology of Malaria in an Area Prepared for Clinical Trials in Korogwe, North-eastern Tanzania.

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    Site preparation is a pre-requesite in conducting malaria vaccines trials. This study was conducted in 12 villages to determine malariometric indices and associated risk factors, during long and short rainy seasons, in an area with varying malaria transmission intensities in Korogwe district, Tanzania. Four villages had passive case detection (PCD) of fever system using village health workers. Four malariometric cross-sectional surveys were conducted between November 2005 and May 2007 among individuals aged 0-19 years, living in lowland urban, lowland rural and highland strata. A total of 10,766 blood samples were collected for malaria parasite diagnosis and anaemia estimation. Blood smears were stained with Giemsa while haemoglobin level was measured by HaemoCue. Socio-economic data were collected between Jan-Apr 2006. Adjusting for the effect of age, the risk of Plasmodium falciparum parasitaemia was significantly lower in both lowland urban, (OR = 0.26; 95%CI: 0.23-0.29, p < 0.001) and highlands, (OR = 0.21; 95%CI: 0.17-0.25, p < 0.001) compared to lowland rural. Individuals aged 6-9 years in the lowland rural and 4-19 years in both lowland urban and highlands had the highest parasite prevalence, whilst children below five years in all strata had the highest parasite density. Prevalence of splenomegaly and gametocyte were also lower in both lowland urban and highlands than in lowland rural. Anaemia (Hb <11 g/dl) prevalence was lowest in the lowland urban. Availability of PCD and higher socio-economic status (SES) were associated with reduced malaria and anaemia prevalence. Higher SES and use of bed nets in the lowland urban could be the important factors for low malaria infections in this stratum. Results obtained here were used together with those from PCD and DSS in selecting a village for Phase 1b MSP3 vaccine trial, which was conducted in the study area in year 2008

    Radiofrequency Ablation of Subpleural Lung Malignancy: Reduced Pain Using an Artificially Created Pneumothorax

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    One of the main issues with radiofrequency (RF) ablation of the subpleural lung malignancy is pain management during and after RF ablation. In this article, we present a case that utilized a technique to decrease the pain associated with RF ablation of a malignancy located within the subpleural lung. Under CT guidance, we created an artificial pneumothorax prior to the RF ablation, which resulted in minimizing the pain usually experienced during and after the procedure. It also decreased the amount of pain medications usually used in patients undergoing RF ablation of a subpleural lung lesion

    Dynamics of conflicts in Wikipedia

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    In this work we study the dynamical features of editorial wars in Wikipedia (WP). Based on our previously established algorithm, we build up samples of controversial and peaceful articles and analyze the temporal characteristics of the activity in these samples. On short time scales, we show that there is a clear correspondence between conflict and burstiness of activity patterns, and that memory effects play an important role in controversies. On long time scales, we identify three distinct developmental patterns for the overall behavior of the articles. We are able to distinguish cases eventually leading to consensus from those cases where a compromise is far from achievable. Finally, we analyze discussion networks and conclude that edit wars are mainly fought by few editors only.Comment: Supporting information adde

    Evidence for the different physiological significance of the 6- and 2-minute walk tests in multiple sclerosis

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    <p>Abstract</p> <p>Background</p> <p>Researchers have recently advocated for the 2-minute walk (2MW) as an alternative for the 6-minute walk (6MW) to assess long distance ambulation in persons with multiple sclerosis (MS). This recommendation has not been based on physiological considerations such as the rate of oxygen consumption (V·O<sub>2</sub>) over the 6MW range.</p> <p>Objective</p> <p>This study examined the pattern of change in V·O<sub>2 </sub>over the range of the 6MW in a large sample of persons with MS who varied as a function of disability status.</p> <p>Method</p> <p>Ninety-five persons with clinically-definite MS underwent a neurological examination for generating an Expanded Disability Status Scale (EDSS) score, and then completion of the 6MW protocol while wearing a portable metabolic unit and an accelerometer.</p> <p>Results</p> <p>There was a time main effect on V·O<sub>2 </sub>during the 6MW (<it>p </it>= .0001) such that V·O<sub>2 </sub>increased significantly every 30 seconds over the first 3 minutes of the 6MW, and then remained stable over the second 3 minutes of the 6MW. This occurred despite no change in cadence across the 6MW (<it>p </it>= .84).</p> <p>Conclusions</p> <p>The pattern of change in V·O<sub>2 </sub>indicates that there are different metabolic systems providing energy for ambulation during the 6MW in MS subjects and steady state aerobic metabolism is reached during the last 3 minutes of the 6MW. By extension, the first 3 minutes would represent a test of mixed aerobic and anaerobic work, whereas the second 3 minutes would represent a test of aerobic work during walking.</p

    Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

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    DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi
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