The possible enzymatic differences between cattle and sheep in their response to ergot alkaloids

Ergotamine is an ergot alkaloid associated with fescue toxicosis of livestock who have grazed endophyte-infected fescue. High performance liquid chromatography (HPLC) was used to detect individual or species-specific differences in the metabolism of ergotamine by liver cytochrome P450 of sheep and cattle. Livers were collected from four steers and two sheep. The diet of the steers used in this study consisted of two being fed a grain diet, one steer grazing endophyte-infected fescue, and the final steer grazing endophyte-free fescue. The two lambs were both fed a grain diet. Livers were prepared and examined for the disappearance of ergotamine and its isomer by HPLC analysis. Liver microsomes from cattle appeared to metabolize ergotamine to a greater degree than those from sheep. There were no apparent differences in the metabolism of ergotamine when comparing cattle that grazed endophyte-infected fescue to cattle that grazed endophyte-free fescue. Therefore, diet had no effect on the metabolism rate of ergotamine. This work provides insight into the possible genetic differences between speciesspecific and individual animals. Further study of such differences should improve breeding programs and produce animals that can more effectively tolerate fescue toxins

The Recent Star Formation in NGC 6822: an Ultraviolet Study

We characterize the star formation in the low-metallicity galaxy NGC 6822 over the past few hundred million years, using GALEX far-UV (FUV, 1344-1786 A) and near-UV (NUV, 1771-2831 A) imaging, and ground-based Ha imaging. From GALEX FUV image, we define 77 star-forming (SF) regions with area >860 pc^2, and surface brightness <=26.8 mag(AB)arcsec^-2, within 0.2deg (1.7kpc) of the center of the galaxy. We estimate the extinction by interstellar dust in each SF region from resolved photometry of the hot stars it contains: E(B-V) ranges from the minimum foreground value of 0.22mag up to 0.66+-0.21mag. The integrated FUV and NUV photometry, compared with stellar population models, yields ages of the SF complexes up to a few hundred Myr, and masses from 2x10^2 Msun to 1.5x10^6 Msun. The derived ages and masses strongly depend on the assumed type of interstellar selective extinction, which we find to vary across the galaxy. The total mass of the FUV-defined SF regions translates into an average star formation rate (SFR) of 1.4x10^-2 Msun/yr over the past 100 Myr, and SFR=1.0x10^-2 Msun/yr in the most recent 10 Myr. The latter is in agreement with the value that we derive from the Ha luminosity, SFR=0.008 Msun/yr. The SFR in the most recent epoch becomes higher if we add the SFR=0.02 Msun/yr inferred from far-IR measurements, which trace star formation still embedded in dust (age <= a few Myr).Comment: Accepted for publication in ApJ, 21 pages, 6 figures, 3 table

Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male

The opacity (Opa) proteins of Neisseria gonorrhoeae are a family of outer membrane proteins demonstrating phase and antigenic variation. N. gonorrhoeae strain FA0190 has 11 opa loci that encode at least 8 antigenically distinct Opa proteins. To determine if expression of one Opa protein or a subset of them is favored during gonococcal infection, we inoculated Opa-negative variants of strain FA1090 intraurethrally into male volunteers. The Opa phenotype of gonococci isolated from urine and urethral swab cultures from nine infected subjects was determined. Opa proteins were expressed in a large proportion of the reisolates from the infected subjects. Gonococci cultured from urine or urethral swab samples from six of the subjects were uniformly Opa positive, with the predominant Opa variants differing among subjects. Three different Opa proteins were represented as the predominant type in at least one subject each. In three subjects, there was more heterogeneity in Opa phenotype of the reisolates, including the presence of Opa-negative variants. An increase in the proportion of isolates expressing multiple Opa proteins occurred over time in most subjects. Passage of the inoculum in vitro did not result in similar changes in Opa expression. There was no detectable difference in infectivity of an Opa-negative variant and one expressing an Opa protein (OpaF) that was highly represented in reisolates from the original nine subjects. Reisolates from three infected volunteers inoculated with the OpaF variant showed continued expression of OpaF alone or in conjunction with other Opa proteins. These results demonstrate that there is strong selection for expression of one or more Opa proteins by strain FA1090 in vivo, but that no single protein is preferentially expressed during early infection in the male urethra

Australian spiny mountain crayfish and their temnocephalan ectosymbionts: an ancient association on the edge of coextinction?

Australian spiny mountain crayfish (Euastacus, Parastacidae) and their ecotosymbiotic temnocephalan flatworms (Temnocephalida, Platyhelminthes) may have co-occurred and interacted through deep time, during a period of major environmental change. Therefore, reconstructing the history of their association is of evolutionary, ecological, and conservation significance. Here, time-calibrated Bayesian phylogenies of Euastacus species and their temnocephalans (Temnohaswellia and Temnosewellia) indicate near-synchronous diversifications from the Cretaceous. Statistically significant cophylogeny correlations between associated clades suggest linked evolutionary histories. However, there is a stronger signal of codivergence and greater host specificity in Temnosewellia, which co-occurs with Euastacus across its range. Phylogeography and analyses of evolutionary distinctiveness (ED) suggest that regional differences in the impact of climate warming and drying had major effects both on crayfish and associated temnocephalans. In particular, Euastacus and Temnosewellia show strong latitudinal gradients in ED and, conversely, in geographical range size, with the most distinctive, northern lineages facing the greatest risk of extinction. Therefore, environmental change has, in some cases, strengthened ecological and evolutionary associations, leaving host-specific temnocephalans vulnerable to coextinction with endangered hosts. Consequently, the extinction of all Euastacus species currently endangered (75%) predicts coextinction of approximately 60% of the studied temnocephalans, with greatest loss of the most evolutionarily distinctive lineages

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10$^{−35}$ and <10$^{−8}$ respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10$^{−6}$). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10$^{−20}$) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue

Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-08, pub-electronic 2021-07-12Publication status: PublishedBiomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFα, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency

An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

Abstract: It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes

Evaluating evidence-based content, features of exercise instruction, and expert involvement in physical activity apps for pregnant women: systematic search and content analysis

Background: Guidelines for physical activity and exercise during pregnancy recommend that all women without contraindications engage in regular physical activity to improve both their own health and the health of their baby. Many women are uncertain how to safely engage in physical activity and exercise during this life stage and are increasingly using mobile apps to access health-related information. However, the extent to which apps that provide physical activity and exercise advice align with current evidence-based pregnancy recommendations is unclear. Objective: This study aims to conduct a systematic search and content analysis of apps that promote physical activity and exercise in pregnancy to examine the alignment of the content with current evidence-based recommendations; delivery, format, and features of physical activity and exercise instruction; and credentials of the app developers. Methods: Systematic searches were conducted in the Australian App Store and Google Play Store in October 2020. Apps were identified using combinations of search terms relevant to pregnancy and exercise or physical activity and screened for inclusion (with a primary focus on physical activity and exercise during pregnancy, free to download or did not require immediate paid subscription, and an average user rating of ≥4 out of 5). Apps were then independently reviewed using an author-designed extraction tool. Results: Overall, 27 apps were included in this review (Google Play Store: 16/27, 59%, and App Store: 11/27, 41%). Two-thirds of the apps provided some information relating to the frequency, intensity, time, and type principles of exercise; only 11% (3/27) provided this information in line with current evidence-based guidelines. Approximately one-third of the apps provided information about contraindications to exercise during pregnancy and referenced the supporting evidence. None of the apps actively engaged in screening for potential contraindications. Only 15% (4/27) of the apps collected information about the user’s current exercise behaviors, 11% (3/27) allowed users to personalize features relating to their exercise preferences, and a little more than one-third provided information about developer credentials. Conclusions: Few exercise apps designed for pregnancy aligned with current evidence-based physical activity guidelines. None of the apps screened users for contraindications to physical activity and exercise during pregnancy, and most lacked appropriate personalization features to account for an individual’s characteristics. Few involved qualified experts during the development of the app. There is a need to improve the quality of apps that promote exercise in pregnancy to ensure that women are appropriately supported to engage in exercise and the potential risk of injury, complications, and adverse pregnancy outcomes for both mother and child is minimized. This could be done by providing expert guidance that aligns with current recommendations, introducing screening measures and features that enable personalization and tailoring to individual users, or by developing a recognized system for regulating apps