| 1111. |
- G., Aad, et al.
(author)
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Searches for electroweak production of supersymmetric particles with compressed mass spectra in s =13 TeV pp collisions with the ATLAS detector
- 2020
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In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 101:5
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Journal article (peer-reviewed)abstract
- This paper presents results of searches for the electroweak production of supersymmetric particles in models with compressed mass spectra. The searches use 139 fb-1 of s=13 TeV proton-proton collision data collected by the ATLAS experiment at the Large Hadron Collider. Events with missing transverse momentum and two same-flavor, oppositely charged, low-transverse-momentum leptons are selected, and are further categorized by the presence of hadronic activity from initial-state radiation or a topology compatible with vector-boson fusion processes. The data are found to be consistent with predictions from the Standard Model. The results are interpreted using simplified models of R-parity-conserving supersymmetry in which the lightest supersymmetric partner is a neutralino with a mass similar to the lightest chargino, the second-to-lightest neutralino, or the slepton. Lower limits on the masses of charginos in different simplified models range from 193 to 240 GeV for moderate mass splittings, and extend down to mass splittings of 1.5 to 2.4 GeV at the LEP chargino bounds (92.4 GeV). Similar lower limits on degenerate light-flavor sleptons extend up to masses of 251 GeV and down to mass splittings of 550 MeV. Constraints on vector-boson fusion production of electroweak SUSY states are also presented. © 2020 CERN.
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| 1112. |
- Gabery, Sanaz, et al.
(author)
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Early white matter pathology in the fornix of the limbic system in Huntington disease
- 2021
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 142:5, s. 791-806
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Journal article (peer-reviewed)abstract
- Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The typical motor symptoms have been associated with basal ganglia pathology. However, psychiatric and cognitive symptoms often precede the motor component and may be due to changes in the limbic system. Recent work has indicated pathology in the hypothalamus in HD but other parts of the limbic system have not been extensively studied. Emerging evidence suggests that changes in HD also include white matter pathology. Here we investigated if the main white matter tract of the limbic system, the fornix, is affected in HD. We demonstrate that the fornix is 34% smaller already in prodromal HD and 41% smaller in manifest HD compared to controls using volumetric analyses of MRI of the IMAGE-HD study. In post-mortem fornix tissue from HD cases, we confirm the smaller fornix volume in HD which is accompanied by signs of myelin breakdown and reduced levels of the transcription factor myelin regulating factor but detect no loss of oligodendrocytes. Further analyses using RNA-sequencing demonstrate downregulation of oligodendrocyte identity markers in the fornix of HD cases. Analysis of differentially expressed genes based on transcription-factor/target-gene interactions also revealed enrichment for binding sites of SUZ12 and EZH2, components of the Polycomb Repressive Complex 2, as well as RE1 Regulation Transcription Factor. Taken together, our data show that there is early white matter pathology of the fornix in the limbic system in HD likely due to a combination of reduction in oligodendrocyte genes and myelin break down.
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| 1113. |
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| 1114. |
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| 1115. |
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| 1116. |
- Hamill, V., et al.
(author)
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Repeated Heart Rate Measurement and Cardiovascular Outcomes in Left Ventricular Systolic Dysfunction
- 2015
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In: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 128:10, s. 1102-1108
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Elevated resting heart rate is associated with increased cardiovascular risk, particularly in patients with left ventricular systolic dysfunction. Heart rate is not monitored routinely in these patients. We hypothesized that routine monitoring of heart rate would increase its prognostic value in patients with left ventricular systolic dysfunction. METHODS: We analyzed the relationship between heart rate measurements and a range of adverse cardiovascular outcomes, including hospitalization for worsening heart failure, in the pooled placebo-treated patients from the morBidity-mortality EvAlUaTion of the I-f inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) trial and Systolic Heart failure treatment with the I-f inhibitor ivabradine (SHIFT) Trial, using standard and time-varying covariate Cox proportional hazards models. By adjusting for other prognostic factors, models were fitted for baseline heart rate alone or for time-updated heart rate (latest heart rate) alone or corrected for baseline heart rate or for immediate previous time-updated heart rate. RESULTS: Baseline heart rate was strongly associated with all outcomes apart from hospitalization for myocardial infarction. Time-updated heart rate increased the strengths of associations for all outcomes. Adjustment for baseline heart rate or immediate previous time-updated heart rate modestly reduced the prognostic importance of time-updated heart rate. For hospitalization for worsening heart failure, each 5 beats/min increase in baseline heart rate and time-updated heart rate was associated with a 15% (95% confidence interval, 12-18) and 22% (confidence interval, 19-40) increase in risk, respectively. Even after correction, the prognostic value of time-updated heart rate remained greater. CONCLUSIONS: In patients with left ventricular systolic dysfunction, time-updated heart rate is more strongly related with adverse cardiovascular outcomes than baseline heart rate. Heart rate should be measured to assess cardiovascular risk at all assessments of patients with left ventricular systolic dysfunction. (C) 2015 Elsevier Inc. All rights reserved.
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| 1117. |
- Heyworth, Eleanor R., et al.
(author)
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Heat Stress Affects Facultative Symbiont-Mediated Protection from a Parasitoid Wasp
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Journal article (peer-reviewed)abstract
- Many insects carry facultative bacterial symbionts, which provide benefits including resistance to natural enemies and abiotic stresses. Little is known about how these beneficial phenotypes are affected when biotic or abiotic threats occur simultaneously. The pea aphid (Acyrthosiphon pisum) can host several well-characterized symbiont species. The symbiont known as X-type can protect against both parasitoid wasps and heat stress. Here, we used three pea aphid genotypes that were naturally infected with X-type and the symbiont Spiroplasma sp. We compared aphids coinfected with these two symbionts with those cured from X-type and infected with only Spiroplasma to investigate the ability of X-type to confer benefits to the host when two threats are experienced simultaneously. Our aim is to explore how robust symbiont protection may be outside a benign laboratory environment. Aphids were subjected to heat shock either before or after attack by parasitoid wasps. Under a benign temperature regime, the aphids carrying X-type tended to be better protected from the parasitoid than those cured. When the aphids experienced a heat shock before being parasitized aphids carrying X-type were more susceptible than those cured. Regardless of infection with the symbiont, the aphids benefitted from being heat shocked after parasitization. The results demonstrate how resistance to parasitoid wasps can be strongly environment-dependent and that a beneficial phenotype conferred by a symbiont under controlled conditions in the laboratory does not necessarily equate to a consistently useful effect in natural populations.
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| 1118. |
- Ho, Joshua W. K., et al.
(author)
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Comparative analysis of metazoan chromatin organization
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Journal article (peer-reviewed)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 1119. |
- Hsu, Yi-Hsiang, et al.
(author)
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An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits
- 2010
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 6:6, s. e1000977-
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Journal article (peer-reviewed)abstract
- Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6 x 10(-8)), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6 x 10(-13); SOX6, p = 6.4 x 10(-10)) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation.
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| 1120. |
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