Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3–5 weeks post partum, a randomized, double-blind clinical trial

BACKGROUND: Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. METHODS: 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21–35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. RESULTS: There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). CONCLUSION: The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge

Environmental dependence of the galaxy stellar mass function in the Dark Energy Survey Science Verification Data

Measurements of the galaxy stellar mass function are crucial to understand the formation of galaxies in the Universe. In a hierarchical clustering paradigm it is plausible that there is a connection between the properties of galaxies and their environments. Evidence for environmental trends has been established in the local Universe. The Dark Energy Survey (DES) provides large photometric datasets that enable further investigation of the assembly of mass. In this study we use ~3.2 million galaxies from the (South Pole Telescope) SPT-East field in the DES science verification (SV) dataset. From grizY photometry we derive galaxy stellar masses and absolute magnitudes, and determine the errors on these properties using Monte-Carlo simulations using the full photometric redshift probability distributions. We compute galaxy environments using a fixed conical aperture for a range of scales. We construct galaxy environment probability distribution functions and investigate the dependence of the environment errors on the aperture parameters. We compute the environment components of the galaxy stellar mass function for the redshift range 0.15<z<1.05. For z<0.75 we find that the fraction of massive galaxies is larger in high density environment than in low density environments. We show that the low density and high density components converge with increasing redshift up to z~1.0 where the shapes of the mass function components are indistinguishable. Our study shows how high density structures build up around massive galaxies through cosmic time

High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms.

Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins with innate immune function on the basis of active degradation by the proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens to quantify protein degradation, with high confidence we identified 35 proteins enriched in antiviral restriction factors. A final screen employed a comprehensive panel of viral mutants to predict viral genes that target >250 human proteins. This approach revealed that helicase-like transcription factor (HLTF), a DNA helicase important in DNA repair, potently inhibits early viral gene expression but is rapidly degraded during infection. The functionally unknown HCMV protein UL145 facilitates HLTF degradation by recruiting the Cullin4 E3 ligase complex. Our approach and data will enable further identifications of innate pathways targeted by HCMV and other viruses.This work was supported by a Wellcome Trust Senior Clinical Research Fellowship (108070) to MPW, a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140), MRC Project Grants to GWGW, PT, ECYW and RJS (MR/L018373/1, MR/P001602/1), a Wellcome Trust Programme Grant (WT090323MA) to GWGW, ECYW and PT, and an MRC Programme Grant (MC_UU_12014/3) to AJD. This study was additionally supported by the Cambridge Biomedical Research Centre, UK

High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms.

Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins with innate immune function on the basis of active degradation by the proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens to quantify protein degradation, with high confidence we identified 35 proteins enriched in antiviral restriction factors. A final screen employed a comprehensive panel of viral mutants to predict viral genes that target >250 human proteins. This approach revealed that helicase-like transcription factor (HLTF), a DNA helicase important in DNA repair, potently inhibits early viral gene expression but is rapidly degraded during infection. The functionally unknown HCMV protein UL145 facilitates HLTF degradation by recruiting the Cullin4 E3 ligase complex. Our approach and data will enable further identifications of innate pathways targeted by HCMV and other viruses.This work was supported by a Wellcome Trust Senior Clinical Research Fellowship (108070) to MPW, a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140), MRC Project Grants to GWGW, PT, ECYW and RJS (MR/L018373/1, MR/P001602/1), a Wellcome Trust Programme Grant (WT090323MA) to GWGW, ECYW and PT, and an MRC Programme Grant (MC_UU_12014/3) to AJD. This study was additionally supported by the Cambridge Biomedical Research Centre, UK