191 research outputs found
Vascular Endothelial Growth Factor mRNA Isoforms 120 and 164 are Differentially Regulated Prior to Ovulation
Vascular Endothelial Growth Factor (VEGF) is produced by cells surrounding the egg in the follicle prior to ovulation. If VEGF is inhibited, ovulation does not occur. The VEGF gene can be spliced to produce different protein isoforms which have specific functions. Our objective was to determine if VEGF 120 and 164 mRNA isoforms are differentially regulated in the preovulatory follicle. From our studies, VEGF isoforms are differentially regulated during both CL regression and after a simulated LH surge. Differences observed in VEGF isoform regulation may allow for manipulation of ovulation in the beef cow
Vascular Endothelial Growth Factor mRNA Isoforms 120 and 164 are Differentially Regulated Prior to Ovulation
Vascular Endothelial Growth Factor (VEGF) is produced by cells surrounding the egg in the follicle prior to ovulation. If VEGF is inhibited, ovulation does not occur. The VEGF gene can be spliced to produce different protein isoforms which have specific functions. Our objective was to determine if VEGF 120 and 164 mRNA isoforms are differentially regulated in the preovulatory follicle. From our studies, VEGF isoforms are differentially regulated during both CL regression and after a simulated LH surge. Differences observed in VEGF isoform regulation may allow for manipulation of ovulation in the beef cow
Letrozole: A Steroid-Free Estrous Synchronization Method
Most bovine estrous synchronization protocols utilize progesterone plus estrogen to control ovulation timing. A drug that inhibits estrogen production (Letrozole) may be an alternative, steroid-free synchronization method (not yet commercially available). However, low estrogen can negatively affect the health of follicles/oocytes and impact fertility. To determine its effects, Letrozole was administered intramuscularly while tracking follicle growth and circulating hormones. Letrozole response was variable. Two of three cows experienced delayed luteolysis/ovulation and extended progesterone production. This preliminary data indicates that Letrozole treatment allows normal follicle progression but drug response may vary and little is known about effects on oocyte quality
Reproductive Aging Influences Ovarian Function in Beef Cows
Anti-Müllerian Hormone (AMH) has been associated with follicle number and age of the ovary. Therefore, our hypothesiswas that AMH was a biomarker for both follicle number and ovarian function in the beef cow. Ovaries were collected by flank laparotomy. The number of follicles increased as cows aged from 1.5 to 6 years and began to decrease thereafter; however, the size of the ovary continued to increase with advanced age. Expression of the AMH gene increased with increasing follicle number in 2-year-old beef cows. These results suggest that heifers with larger ovaries will have greater numbers of follicles and greater productivity, allowing them to stay in the production herd longer. AMH could be used to identify heifers of high reproductive potential at a very young age
Attainment and maintenance of pubertal cyclicity may predict reproductive longevity in beef heifers
We hypothesized the manner that heifers achieve puberty may indicate their future reproductive longevity. Heifers with discontinued or delayed cyclicity during puberty attainment may have irregular reproductive cycles, anovulation, and infertility in their first breeding season contributing to a shorter reproductive lifespan. Therefore, plasma progesterone (P4) was measured from weaning to breeding on 611 heifers born 2012–2017 and four pubertal classifications were identified: (1) Early; P4 ≥ 1 ng/ml \u3c March 12 with continued cyclicity, (2) Typical; P4 ≥ 1 ng/ml ≥ March 12 with continued cyclicity, (3) Start-Stop; P4 ≥ 1 ng/ml but discontinued cyclicity, and (4) Non-Cycling; no P4 ≥ 1 ng/ml. Historical herd records indicated that 25% of heifers achieved puberty prior to March 12th in the 10 years prior to the study. Start-Stop and Non-Cycling yearling heifers were lighter indicating reduced growth and reproductive maturity traits compared with Early/Typical heifers. In addition, Non-Cycling/Start-Stop heifers were less responsive to prostaglandin F2 alpha (PGF2α) to initiate estrous behavior and ovulation to be artificially inseminated. Non-Cycling heifers had fewer reproductive tract score-5 and reduced numbers of calves born in the first 21-days-ofcalving during their first breeding season. Within the Start-Stop classification, 50% of heifers reinitiated cyclicity with growth traits and reproductive parameters that were similar to heifers in the Early/Typical classification while those that remained non-cyclic were more similar to heifers in the Non-Cycling group. Thus, heifers with discontinued cyclicity or no cyclicity during puberty attainment had delayed reproductive maturity resulting in subfertility and potentially a shorter reproductive lifespan
Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER
We describe 280 GHz bolometric detector arrays that instrument the
balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to
measure the large-scale B-mode polarization of the cosmic microwave background
in search of the cosmic-inflation, gravitational-wave signature. 280 GHz
channels aid this science goal by constraining the level of B-mode
contamination from galactic dust emission. We present the focal plane unit
design, which consists of a 1616 array of conical, corrugated feedhorns
coupled to a monolithic detector array fabricated on a 150 mm diameter silicon
wafer. Detector arrays are capable of polarimetric sensing via waveguide
probe-coupling to a multiplexed array of transition-edge-sensor (TES)
bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which
in total contains 765 spatial pixels and 1,530 polarization sensitive
bolometers. By fabrication and measurement of single feedhorns, we demonstrate
14.7 FHWM Gaussian-shaped beams with 1% ellipticity in a 30%
fractional bandwidth centered at 280 GHz. We present electromagnetic
simulations of the detection circuit, which show 94% band-averaged,
single-polarization coupling efficiency, 3% reflection and 3% radiative loss.
Lastly, we demonstrate a low thermal conductance bolometer, which is
well-described by a simple TES model and exhibits an electrical noise
equivalent power (NEP) = 2.6 10 W/,
consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201
Method for Assigning Priority Levels in Acute Care (MAPLe-AC) predicts outcomes of acute hospital care of older persons - a cross-national validation
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Although numerous risk factors for adverse outcomes for older persons after an acute hospital stay have been : identified, a decision making tool combining all available information in a clinically meaningful way would be helpful for daily hospital practice. The purpose of this study was to evaluate the ability of the Method for Assigning Priority Levels for Acute Care (MAPLe-AC) to predict adverse outcomes in acute care for older people and to assess its usability as a decision making tool for discharge planning. METHODS: Data from a prospective multicenter study in five Nordic acute care hospitals with information from admission to a one year follow-up of older acute care patients were compared with a prospective study of acute care patients from admission to discharge in eight hospitals in Canada. The interRAI Acute Care assessment instrument (v1.1) was used for data collection. Data were collected during the first 24 hours in hospital, including pre-morbid and admission information, and at day 7 or at discharge, whichever came first. Based on this information a crosswalk was developed from the original MAPLe algorithm for home care settings to acute care (MAPLe-AC). The sample included persons 75 years or older who were admitted to acute internal medical services in one hospital in each of the five Nordic countries (n = 763) or to acute hospital care either internal medical or combined medical-surgical services in eight hospitals in Ontario, Canada (n = 393). The outcome measures considered were discharge to home, discharge to institution or death. Outcomes in a 1-year follow-up in the Nordic hospitals were: living at home, living in an institution or death, and survival. Logistic regression with ROC curves and Cox regression analyses were used in the analyses. RESULTS: Low and mild priority levels of MAPLe-AC predicted discharge home and high and very high priority levels predicted adverse outcome at discharge both in the Nordic and Canadian data sets, and one-year outcomes in the Nordic data set. The predictive accuracy (AUC's) of MAPLe-AC's was higher for discharge outcome than one year outcome, and for discharge home in Canadian hospitals but for adverse outcome in Nordic hospitals. High and very high priority levels in MAPLe-AC were also predictive of days to death adjusted for diagnoses in survival models. CONCLUSION: MAPLe-AC is a valid algorithm based on risk factors that predict outcomes of acute hospital care. It could be a helpful tool for early discharge planning although further testing for active use in clinical practice is still needed.Reykjavik Hospital Research Fund
St. Joseph's Research Fund, Iceland
Norwegian Medical Society
2
Diakonhjemmet Hospital
Diakonhjemmet University College
Diakonhjemmet Research Fund, Norway
Sweden's Lions Fund, Sweden
Health Transition Fund
Health Canada
Canadian Institutes for Health Research (CIHR)
Nordic Lions Red Feather Fund
Nordic Council of Ministers
Roikjer Fund, Denmark
Finnish Lions Fund, Finland
Icelandic Lions Fund
Memorial Fund of Helgu Jensdottur and Sigurliða Kristjanssona
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
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