103 research outputs found
Goats as Valuable Animal Model to Test the Targeted Glutamate Supplementation upon Antral Follicle Number, Ovulation Rate, and LH-Pulsatility
The potential effect of intravenous administration of glutamate on the ovarian activity and the LH secretion pattern, considering the anestrous yearling goat as an animal model, were assessed. In late April, yearling goats (n = 20) were randomly assigned to either (1) Glutamate supplemented (GLUT; n = 10, Live Weight (LW) = 29.6 ± 1.02 kg, Body Condition (BCS) = 3.4 ± 0.2 units; i.v. supplemented with 7 mg GLUT kgâ1 LW) or (2) Non-supplemented (CONT; n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2 units; i.v. saline). The oats were estrus-synchronized; blood sampling (6 h Ă 15 min) was carried out for LH quantification. Response variables included pulsatility (PULSE), time to first pulse (TTFP), amplitude (AMPL), nadir (NAD), and area under the curve (AUC) of LH. Ovaries were ultra-sonographically scanned to assess ovulation rate (OR), number of antral follicles (AF), and total ovarian activity (TOA = OR + AF). LH-PULSE was quantified with the Munro algorithm; significant treatment x time interactions were evaluated across time. The variables LW and BCS did not differ (p > 0.05) between the experimental groups. Nevertheless, OR (1.77 vs. 0.87 ± 0.20 units), TOA (4.11 vs. 1.87 ± 0.47 units) and LH-PULSE (5.0 vs. 2.2 pulses 6 h-1) favored (p < 0.05) to the GLUT group. Our results reveal that targeted glutamate supplementation, the main central nervous system neurotransmitter, arose as an interesting strategy to enhance the hypothalamicâhypophysealâovarian response considering the anestrous-yearling goat as an animal model, with thought-provoking while promising translational applications
Does Size Matters? Relationships among Social Dominance and Some Morphometric Traits upon Out-of-Season Reproductive Outcomes in Anestrus Dairy Goats Treated with P4 + eCG
The possible role of the social rank (R) (i.e., low-LSR, middle-MSR, or high-HSR) in anestrus goats exposed to a P4 + eCG (D) (i.e., 100 or 350 IU) estrus induction protocol (EIP) was evaluated. Goats (Alpine-Saanen-Nubian à Criollo; n = 70; 25° North) managed under stall-fed conditions were all ultrasound evaluated to confirm anestrous status, while the social rank was determined 30 d prior to the EIP. The response variables included estrus induction (EI, %), duration of estrus (DUR, h), ovulation rate (OR, n), live weight (LW, kg), thoracic perimeter (TP, cm), thoracic diameter (TD, cm), body length (BL, cm), height at withers (HW, cm), beard length (BEA, cm), compactness index (COM, cm), and anamorphosis index (ANA, cm), as affected by R, D, and the R à D interaction were evaluated, while the correlation coefficients among reproductive and morphometric variables were quantified. An R à D interaction (p 0.05) with any response variable, either reproductive or morphometric. As expected, LW had high correlation coefficients (p < 0.01) with TP (0.86), TD (0.88), BL (0.82), HW (0.75), BEA (0.51), COM (0.97), and ANA (0.75). In general, the morphometric variables as a whole demonstrated important correlation coefficients among them (p < 0.01), ranging from 0.38 up to 0.84. To estimate the importance of the morphometric differences between social rank upon estrus induction, a principal component (PC) analysis was performed based on the correlation matrix derived from the corporal measurements. The PC1 and PC2 explained 70.3% and 17.6% of the morphometric variation, respectively. The PC1 was a measure of the goat size (i.e., small, medium, large) and its association with estrus occurrence was evaluated using a logistic regression model; the bigger the goat, the increased probability of being in estrus, by up to five times compared to small goats. Our results confirm that the higher social ranked, larger goats amalgamated some fundamental factors to be successful: aggressiveness, primacy to food access, augmented live weight, and corporal size; all of these were able to modulate out-of-season reproductive success in crossbred dairy goats subjected to an estrus induction protocol and managed under stall-fed conditions in Northern Mexico
2005- 2008 UNLV McNair Journal
Journal articles based on research conducted by undergraduate students in the McNair Scholars Program
Table of Contents
Biography of Dr. Ronald E. McNair
Statements:
Dr. Neal J. Smatresk, UNLV President
Dr. Juanita P. Fain, Vice President of Student Affairs
Dr. William W. Sullivan, Associate Vice President for Retention and Outreach
Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach
McNair Scholars Institute Staf
Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes
Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodiumâglucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with reninâangiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3â5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (Nâ=â1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3â5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007â2013 under grant agreement no. HEALTH-F2-2013â601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundationâs Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1â19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska LĂ€karesĂ€llskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215â2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Unionâs Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
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