83 research outputs found

    An assessment of scup (Stenotomus chrysops) and black sea bass (Centropristas striata) discards in the directed otter trawl fisheries in the Mid-Atlantic Bight

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    This study was undertaken to re-assess the level of scup (Stenotomus chrysops) discards by weight and to evaluate the effect of various codend mesh sizes on the level of scup discards in the winter-trawl scup fishery. Scup discards were high in directed scup tows regardless of codend mesh — typically one to five times the weight of landings. The weight of scup discards in the present study did not differ significantly from that recorded in scup-targeted tows in the NMFS observer database. Most discards were required as such by the 22.86 cm TL (total length) fish-size limit for catches. Mesh sizes ≤12.7 cm, including the current legal mesh size (11.43 cm) did not adequately filter out scup smaller than 22.86 cm. The median length of scup discards was about 19.83 cm TL. Lowering the legal size for scup from 22.86 to 19.83 cm TL would greatly reduce discard mortality. Scup discards were a small fraction (0.4%) of black sea bass (Centropristis striata) landings in blacksea-bass−targeted tows. The black sea bass fishery is currently regulated under the small-mesh fishery gearrestricted area plan in which fishing is prohibited in some areas to reduce scup mortality. Our study found no evidence to support the efficacy of this management approach. The expectations that discarding would increase disproportionately as the trip limit (limit [in kilograms] on catch for a species) was reached towards the end of the trip and that discards would increase when the trip limit was reduced from 4536 kg to 454 kg at the end of the directed fishing season were not supported. Trip limits did not significantly affect discard mortality

    Protective Unfolded Protein Response in Human Pancreatic Beta Cells Transplanted into Mice

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    Background: There is great interest about the possible contribution of ER stress to the apoptosis of pancreatic beta cells in the diabetic state and with islet transplantation. Methods and Findings: Expression of genes involved in ER stress were examined in beta cell enriched tissue obtained with laser capture microdissection (LCM) from frozen sections of pancreases obtained from non-diabetic subjects at surgery and from human islets transplanted into ICR-SCID mice for 4 wk. Because mice have higher glucose levels than humans, the transplanted beta cells were exposed to mild hyperglycemia and the abnormal environment of the transplant site. RNA was extracted from the LCM specimens, amplified and then subjected to microarray analysis. The transplanted beta cells showed an unfolded protein response (UPR). There was activation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress, increased expression of ER chaperones and ERAD (ER-associated protein degradation) proteins. The other two arms of ER stress, PERK and ATF-6, had many down regulated genes. Downregulation of EIF2A could protect by inhibiting protein synthesis. Two genes known to contribute to apoptosis, CHOP and JNK, were downregulated. Conclusions: Human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins

    Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.

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    Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles), and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i) reduced trypsin binding activity, (ii) increased chaperone activity, and (iii) increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine) effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.Early Career Fellowship from the National Health and Medical Research Council GNT1012521(A.R.W.); Wellcome Trust Programme Grant (J.R.K., C.M.D.) 094425/Z/10/Z; Samsung GRO Grant (M.R.W.)This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013003

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Energy Levels of Light Nuclei. III

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    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Vessel time allocation in the US Illex illecebrosus fishery

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    The Illex illecebrosus fishery in the northwestern Atlantic Ocean is trawl-based. I. illecebrosus normally lives less than 1 year. One option for managing such a short-lived species is the use of catch and effort data obtained from fishing vessels during the fishing season to manage the fishery in real time. Verification of the accuracy of data reports is important. Conceivably, information contained in the data stream of vessel position and time provided by a remote data logger could be used to reconstruct the vessel’s activities to assess the reliability of industry reports. This study describes quantitatively the types of vessel operating activities that take place on a typical I. illecebrosus fishing trip and assesses the possibility of reconstructing these activities reliably from the simple data stream of vessel position and time. Seven activities were identified, six of which occurred commonly: steaming to and from port, searching, towing, set-up time between tows, steaming overnight and laying-to overnight. Processing the catch, as a discrete activity, occurred rarely. Each activity could be characterized in terms of its duration and distance traveled, the average vessel speed, and the tendency for vessel speed to change during the activity. Most activities were conducted in a linear manner. Accordingly, reasonable estimates of the distance and duration of these activities could be obtained simply from the knowledge of the starting and ending position and time. Analysis of search time and subsequent catch revealed that searching did not improve catch. More squid would have been caught had the vessels used this time for towing. Catch per unit effort (CPUE) can be calculated using duration or distance in the denominator. In this set of fishing trips, the two were equivalent. Catch bore a nonlinear relationship with CPUE. In particular, larger catches were associated with incrementally larger CPUEs. The uniqueness of each activity when described by its characteristic speed, duration and distance, and the consistency of these characteristics for each activity between vessels suggests that vessel behavior might be assessed remotely using a time series of position and time. Such a capability might be important in any real-time management plan where industry vessels necessarily must be depended upon for data on catch and CPUE

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    Patterns of prophylactic gastrostomy tube placement in head and neck cancer patients: A consideration of the significance of social support and practice variation

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    OBJECTIVES/HYPOTHESIS: The purpose of this study was to examine factors associated with prophylactic placement of feeding tubes in head and neck cancer patients receiving radiation therapy as a part of treatment using multilevel models that account for patient-, physician-, and institution-level sources of variation. STUDY DESIGN: A retrospective analysis using binary logistic regression and hierarchical linear models was run to evaluate independent predictors of prophylactic feeding tube placement. METHODS: Surveillance, Epidemiology, and End Results-Medicare data were used. Head and neck cancer patients diagnosed with locoregionally advanced stage disease from 2000 to 2005 were included in this study (N = 8,306). RESULTS: Across all models, prophylactic gastrostomy tube placement was found to be more likely in patients who had cancer of the larynx or oropharynx compared with those with cancer of the nasopharynx or oral cavity; who had regional instead of local cancer; who did not receive surgery as a part of treatment, but did receive chemotherapy; and who were divorced, separated, or widowed. Additionally, although practice variation was observed to occur, its overall contribution in predicting prophylactic gastrostomy tube placement was minimal. CONCLUSIONS: As health care enters an era of patient-centered care, further investigation of the potential role of social support (or lack of social support) in influencing treatment decisions of head and neck cancer patients and providers is warranted. LEVEL OF EVIDENCE: 2b Laryngoscope, 2013. Society, Inc
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