118 research outputs found
An Applied Framework for Incorporating Multiple Sources of Uncertainty in Fisheries Stock Assessments
Estimating fish stock status is very challenging given the many sources and high levels of
uncertainty surrounding the biological processes (e.g. natural variability in the demographic
rates), model selection (e.g. choosing growth or stock assessment models) and parameter
estimation. Incorporating multiple sources of uncertainty in a stock assessment allows
advice to better account for the risks associated with proposed management options, pro-
moting decisions that are more robust to such uncertainty. However, a typical assessment
only reports the model fit and variance of estimated parameters, thereby underreporting the
overall uncertainty. Additionally, although multiple candidate models may be considered,
only one is selected as the ‘best’ result, effectively rejecting the plausible assumptions
behind the other models. We present an applied framework to integrate multiple sources of
uncertainty in the stock assessment process. The first step is the generation and condition-
ing of a suite of stock assessment models that contain different assumptions about the
stock and the fishery. The second step is the estimation of parameters, including fitting of
the stock assessment models. The final step integrates across all of the results to reconcile
the multi-model outcome. The framework is flexible enough to be tailored to particular
stocks and fisheries and can draw on information from multiple sources to implement a
broad variety of assumptions, making it applicable to stocks with varying levels of data avail-
ability The Iberian hake stock in International Council for the Exploration of the Sea (ICES)
Divisions VIIIc and IXa is used to demonstrate the framework, starting from length-based
stock and indices data. Process and model uncertainty are considered through the growth,
natural mortality, fishing mortality, survey catchability and stock-recruitment relationship.
Estimation uncertainty is included as part of the fitting process. Simple model averaging is
used to integrate across the results and produce a single assessment that considers the
multiple sources of uncertainty.Versión del edito
Structural Determinants for Ligand-Receptor Conformational Selection in a Peptide G Protein-coupled Receptor
G protein coupled receptors (GPCRs) modulate the majority of physiological processes through specific intermolecular interactions with structurally diverse ligands and activation of differential intracellular signaling. A key issue yet to be resolved is how GPCRs developed selectivity and diversity of ligand binding and intracellular signaling during evolution. We have explored the structural basis of selectivity of naturally occurring gonadotropin-releasing hormones (GnRHs) from different species in the single functional human GnRH receptor. We found that the highly variable amino acids in position 8 of the naturally occurring isoforms of GnRH play a discriminating role in selecting receptor conformational states. The human GnRH receptor has a higher affinity for the cognate GnRH I but a lower affinity for GnRH II and GnRHs from other species possessing substitutions for Arg(8). The latter were partial agonists in the human GnRH receptor. Mutation of Asn(7.45) in transmembrane domain (TM) 7 had no effect on GnRH I affinity but specifically increased affinity for other GnRHs and converted them to full agonists. Using molecular modeling and site-directed mutagenesis, we demonstrated that the highly conserved Asn(7.45) makes intramolecular interactions with a highly conserved Cys(6.47) in TM 6, suggesting that disruption of this intramolecular interaction induces a receptor conformational change which allosterically alters ligand specific binding sites and changes ligand selectivity and signaling efficacy. These results reveal GnRH ligand and receptor structural elements for conformational selection, and support co-evolution of GnRH ligand and receptor conformations
Inter-annual variability in the effects of riparian woodland on micro-climate, energy exchanges and water temperature of an upland Scottish stream
Improving the early identification of COVID-19 pneumonia:a narrative review
Delayed presentation of COVID-19 pneumonia increases the risk of mortality and need for high-intensity healthcare. Conversely, early identification of COVID-19 pneumonia grants an opportunity to intervene early and thus prevent more complicated, protracted and less successful hospital admissions. To improve the earlier detection of COVID-19 pneumonia in the community we provide a narrative review of current evidence examining the clinical parameters associated with early disease progression. Through an evolving literature review, we examined: the symptoms that may suggest COVID-19 progression; the timing of deterioration; the utility of basic observations, clinical examination and chest X-ray; the value of postexertion oxygen saturations; and the use of CRP to monitor disease progression. We go on to discuss the challenges in monitoring the COVID-19 patient in the community and discuss thresholds for further assessment. Confusion, persistent fever and shortness of breath were identified as worrying symptoms suggestive of COVID-19 disease progression necessitating urgent clinical contact. Importantly, a significant proportion of COVID-19 pneumonia patients appear not to suffer dyspnoea despite severe disease. Patients with this asymptomatic hypoxia seem to have a poorer prognosis. Such patients may present with other signs of hypoxia: severe fatigue, exertional fatigue and/or altered mental status. We found duration of symptoms to be largely unhelpful in determining risk, with evidence of deterioration at any point in the disease. Basic clinical parameters (pulse, respiratory rate, blood pressure, temperature and oxygen saturations (SpO(2))) are likely of high value in detecting the deteriorating community COVID-19 patient and/or COVID-19 mimickers/complications (eg, sepsis, bacterial pneumonia and pulmonary embolism). Of these, SpO(2) carried the greatest utility in detecting COVID-19 progression. CRP is an early biochemical parameter predictive of disease progression and used appropriately is likely to contribute to the early identification of COVID-19 pneumonia. Identifying progressive COVID-19 in the community is feasible using basic clinical questions and measurements. As such, if we are to limit the mortality, morbidity and the need for complicated, protracted admissions, monitoring community COVID-19 cases for signs of deterioration to facilitate early intervention is a viable strategy
A spatio-temporal statistical model of maximum daily river temperatures to inform the management of Scotland's Atlantic salmon rivers under climate change
Faculty Senate Resolution on the Performing Arts Center, adopted on September 14, 1978
A spatio-temporal statistical model of maximum daily river temperatures to inform the management of Scotland's Atlantic salmon rivers under climate change
Developmental profile and sexually dimorphic expression of kiss1 and kiss1r in the fetal mouse brain
The hypothalamic-pituitary-gonadal axis (HPG) is a complex neuroendocrine circuit involving multiple levels of regulation. Kisspeptin neurons play essential roles in controlling the HPG axis from the perspectives of puberty onset, oscillations of gonadotropin releasing hormone (GnRH) neuron activity and the pre-ovulatory LH surge. The current studies focus on the expression of kisspeptin during murine fetal development using in situ hybridization (ISH), quantitative reverse transcription real-time PCR (QPCR) and immunocytochemistry. Expression of mRNA coding for kisspeptin (KISS1) and its receptor KISS1R was observed at embryonic (E) day 13 by ISH. At E13 and other later ages examined, Kiss1 signal in individual cells within the arcuate nucleus (ARC) appeared stronger in females than males. ISH examination of agonadal steroidogenic factor-1 (Sf1) knockout mice revealed that E17 XY knockouts resembled wild-type XX females. These findings raise the possibility that gonadal hormones modulate the expression of Kiss1 in the ARC prior to birth. The sex and genotype differences were tested quantitatively by QPCR experiments in dissected hypothalami from mice at E17 and adulthood. Females had significantly more Kiss1 than males at both ages, even though the number of cells detected by ISH was similar. In addition, QPCR revealed a significant difference in the amount of Kiss1 mRNA in Sf1 mice with wild-type (WT) XY mice expressing less than XY knockouts (KO) and XX mice of both genotypes. The detection of immunoreactive KISS1 in perikarya of the ARC at E17 indicates that early mRNA is translated to peptide. The functional significance of this early expression of Kiss1 awaits elucidation
Vancomycin wrap for anterior cruciate ligament surgery
Background:
The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft.
Purpose:
To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR.
Study Design:
Controlled laboratory study.
Methods:
Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression.
Results:
Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05).
Conclusion:
Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment.
Clinical Relevance:
Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity
Identification of androgen receptor phosphorylation in the primate ovary in vivo
The androgen receptor (AR) is a member of the nuclear receptor superfamily, and is important for both male and female reproductive health. The receptor is a target for a number of post-translational modifications including phosphorylation, which has been intensively studied in vitro. However, little is known about the phosphorylation status of the receptor in target tissues in vivo. The common marmoset is a useful model for studying human reproductive functions, and comparison of the AR primary sequence from this primate shows high conservation of serines known to be phosphorylated in the human receptor and corresponding flanking amino acids. We have used a panel of phosphospecific antibodies to study AR phosphorylation in the marmoset ovary throughout the follicular phase and after treatment with GNRH antagonist or testosterone propionate. In normal follicular phase ovaries, total AR (both phosphorylated and non-phosphorylated forms) immunopositive staining was observed in several cell types including granulosa cells of developing follicles, theca cells and endothelial cells lining blood vessels. Receptor phosphorylation at serines 81, 308, and 650 was detected primarily in the granulosa cells of developing follicles, surface epithelium, and vessel endothelial cells. Testosterone treatment lead to a modest increase in AR staining in all stages of follicle studied, while GNRH antagonist had no effect. Neither treatment significantly altered the pattern of phosphorylation compared to the control group. These results demonstrate that phosphorylation of the AR occurs, at a subset of serine residues, in a reproductive target tissue in vivo, which appears refractory to hormonal manipulations
Phospholipase C-eta enzymes as putative protein kinase C and Ca2+ signalling components in neuronal and neuroendocrine tissues
Phosphoinositol-specific phospholipase C enzymes (PLCs) are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C activation. A sixth class of phosphoinositol-specific PLC with a novel domain structure, PLC-eta (PLCeta) has recently been discovered in mammals. Recent research, reviewed here, shows that this class consists of two enzymes, PLCeta1 and PLCeta2. Both enzymes hydrolyze phosphatidylinositol 4,5-bisphosphate and are more sensitive to Ca2+ than other PLC isozymes and are likely to mediate G-protein-coupled receptor (GPCR) signalling pathways. Both enzymes are expressed in neuron-enriched regions, being abundant in the brain. We demonstrate that they are also expressed in neuroendocrine cell lines. PLCeta enzymes therefore represent novel proteins influencing intracellular Ca2+ dynamics and protein kinase C activation in the brain and neuroendocrine systems as putative mediation of GPCR regulation
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