826 research outputs found

    CemOrange2 fusions facilitate multifluorophore subcellular imaging in C. elegans

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    Due to its ease of genetic manipulation and transparency, Caenorhabditis elegans (C. elegans) has become a preferred model system to study gene function by microscopy. The use of Aequorea victoria green fluorescent protein (GFP) fused to proteins or targeting sequences of interest, further expanded upon the utility of C. elegans by labeling subcellular structures, which enables following their disposition during development or in the presence of genetic mutations. Fluorescent proteins with excitation and emission spectra different from that of GFP accelerated the use of multifluorophore imaging in real time. We have expanded the repertoire of fluorescent proteins for use in C. elegans by developing a codon-optimized version of Orange2 (CemOrange2). Proteins or targeting motifs fused to CemOrange2 were distinguishable from the more common fluorophores used in the nematode; such as GFP, YFP, and mKate2. We generated a panel of CemOrange2 fusion constructs, and confirmed they were targeted to their correct subcellular addresses by colocalization with independent markers. To demonstrate the potential usefulness of this new panel of fluorescent protein markers, we showed that CemOrange2 fusion proteins could be used to: 1) monitor biological pathways, 2) multiplex with other fluorescent proteins to determine colocalization and 3) gain phenotypic knowledge of a human ABCA3 orthologue, ABT-4, trafficking variant in the C. elegans model organism

    Heme metabolism genes Downregulated in COPD Cachexia.

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    IntroductionCachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.MethodsWe analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (< 20 kg/m2) and 1/3 criteria: decreased muscle strength (six-minute walk distance < 350 m), anemia (hemoglobin < 12 g/dl), and low fat-free mass index (FFMI) (< 15 kg/m2 among women and < 17 kg/m2 among men) in COPDGene. In ECLIPSE, cachexia was defined as weight-loss > 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB.ResultsThe prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR < 0.05) and ECLIPSE (FDR < 0.05).DiscussionSeveral replicated genes regulating heme metabolism were downregulated among participants with COPD cachexia. Impaired heme biosynthesis may contribute to cachexia development through free-iron buildup and oxidative tissue damage

    Swift J2058.4+0516: Discovery of a Possible Second Relativistic Tidal Disruption Flare?

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    We report the discovery by the Swift hard X-ray monitor of the transient source Swift J2058.4+0516 (Sw J2058+05). Our multi-wavelength follow-up campaign uncovered a long-lived (duration >~ months), luminous X-ray (L_X,iso ~ 3 x 10^47 erg s^-1) and radio (nu L_nu,iso ~ 10^42 erg s^-1) counterpart. The associated optical emission, however, from which we measure a redshift of 1.1853, is relatively faint, and this is not due to a large amount of dust extinction in the host galaxy. Based on numerous similarities with the recently discovered GRB 110328A / Swift J164449.3+573451 (Sw J1644+57), we suggest that Sw J2058+05 may be the second member of a new class of relativistic outbursts resulting from the tidal disruption of a star by a supermassive black hole. If so, the relative rarity of these sources (compared with the expected rate of tidal disruptions) implies that either these outflows are extremely narrowly collimated (theta < 1 degree), or only a small fraction of tidal disruptions generate relativistic ejecta. Analogous to the case of long-duration gamma-ray bursts and core-collapse supernovae, we speculate that rapid spin of the black hole may be a necessary condition to generate the relativistic component. Alternatively, if powered by gas accretion (i.e., an active galactic nucleus [AGN]), Sw J2058+05 would seem to represent a new mode of variability in these sources, as the observed properties appear largely inconsistent with known classes of AGNs capable of generating relativistic jets (blazars, narrow-line Seyfert 1 galaxies).Comment: Minor typos correcte

    Analyzing networks of phenotypes in complex diseases: methodology and applications in COPD

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    Background: The investigation of complex disease heterogeneity has been challenging. Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes. Results: We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD). We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants. Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches. Conclusion: Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease severity, and genetic mechanisms

    An interpretative phenomenological analysis of posttraumatic growth in adults bereaved by suicide

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    This study explored experiences of posttraumatic growth in adults bereaved by suicide. Six participants were interviewed using a semi-structured interview schedule. Transcribed interviews were analyzed from an interpretative phenomenological framework. Two superordinate themes, with three ordinate themes in each, were identified: (a) positive growth (“life view,” “knowledge of self,” and “relation to others”) and (b) social context (“gaze of others,” “public guise,” and “solace of other survivors”). Suicide survivors gain extra insights due to their experiences, but are reluctant to acknowledge that they do. This requires consideration in theoretical and clinical setting

    Bed Bug Infestations in an Urban Environment

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    Bed bug infestations adversely affect health and quality of life, particularly among persons living in homeless shelters

    Model-Independent Global Constraints on New Physics

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    Using effective-lagrangian techniques we perform a systematic survey of the lowest-dimension effective interactions through which heavy physics might manifest itself in present experiments. We do not restrict ourselves to special classes of effective interactions (such as `oblique' corrections). We compute the effects of these operators on all currently well-measured electroweak observables, both at low energies and at the ZZ resonance, and perform a global fit to their coefficients. Despite the fact that a great many operators arise in our survey, we find that most are quite strongly bounded by the current data. We use our survey to systematically identify those effective interactions which are {\it not} well-bounded by the data -- these could very well include large new-physics contributions. Our results may also be used to efficiently confront specific models for new physics with the data, as we illustrate with an example.Comment: plain TeX, 68 pages, 2 figures (postscript files appended), McGill-93/12, NEIPH-93-008, OCIP/C-93-6, UQAM-PHE-93/08, UdeM-LPN-TH-93-15
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