Effect of inbreeding and heritability of sperm competition success in the bulb mite Rhizoglyphus robini

Sperm competition is a potent evolutionary force shaping the reproductive biology of most animal species. Here, we estimated the heritability of sperm competition success in the promiscuous bulb mite Rhizoglyphus robini. Sperm competition success was measured with the sterile male technique as the proportion of eggs fertilised by the second of three males mated with a single female. Sperm competition success responded significantly to selection. The heritability estimated from the response to five generations of selection was 0.13. We also estimated the effect of inbreeding on sperm competition success. Males produced by sib-mating (F=0.25) had a significantly lower sperm competition success than outbred males. The estimated coefficient of inbreeding depression was 0.53. Such high inbreeding depression together with moderately low heritability is consistent with the view that sperm competitive ability is under strong directional selection and strongly influences the reproductive success of males

Strong association between a single gene and fertilization efficiency of males and fecundity of their mates in the bulb mite.

Although variation in male fertilization efficiency has been shown to have a genetic basis in several species, the genes responsible for the effect are generally unknown. Here, we show a strong association between the fertilization success of males and their phosphogluconate dehydrogenase (Pgdh) genotype in the bulb mite Rhizoglyphus robini. Males homozygous for the slow (S) allele fathered a significantly greater proportion of offspring when competing with males homozygous for the fast (F) allele. There was no evidence that female fecundity was influenced by their Pgdh genotype. The fecundity of FF females did not differ significantly from the fecundity of SS females but female fecundity was significantly influenced by the genotype of their mate. Females paired with SS males laid significantly fewer eggs than females paired with FF males. Altogether these data show a trade-off, with the male SS genotype associated with their higher fertilization efficiency but at the cost of a negative impact on the fecundity of females mating with them

Screening for More than 1,000 Pesticides and Environmental Contaminants in Cannabis by GC/Q-TOF

A method has been developed to screen cannabis extracts for more than 1,000 pesticides and environmental pollutants using a gas chromatograph coupled to a high-resolution accurate mass quadrupole time-of-flight mass spectrometer (GC/Q-TOF). An extraction procedure was developed using acetonitrile with solid phase extraction cleanup. Before analysis, extracts were diluted 125:1 with solvent. Two data mining approaches were used together with a retention-time-locked Personal Compound Database and Library (PCDL) containing high-resolution accurate mass spectra for pesticides and other environmental pollutants. (1) A Find-by-Fragments (FbF) software tool extracts several characteristic exact mass ions within a small retention time window where the compound elutes. For each compound in the PCDL, the software evaluates the peak shape and retention time of each ion as well as the monoisotopic exact mass, ion ratios, and other factors to decide if the compound is present or not. (2) A separate approach used Unknowns Analysis (UA) software with a peak-finding algorithm called SureMass to deconvolute peaks in the chromatogram. The accurate mass spectra were searched against the PCDL using spectral matching and retention time as filters. A subset PCDL was generated containing only pesticides that are most likely to be found on foods in the US. With about 250 compounds in the smaller PCDL, there were fewer hits for non-pesticides, and data review was much faster. Organically grown cannabis was used for method development. Twenty-one confiscated cannabis samples were analyzed and ten were found to have no detectable pesticides. The remaining 11 samples had at least one pesticide and one sample had seven detectable residues. Quantitative analysis was run on the confiscated samples for a subset of the pesticides found by screening. Two cannabis samples had residues of carbaryl and malathion that were estimated to be about 10 times greater than the highest US Environmental Protection Agency tolerance set for food and about 4,000 times greater than the Canadian maximum residue limits for dried cannabis flower

Advances in the evolutionary understanding of MHC polymorphism

Radwan J, Babik W, Kaufman J, Lenz TL, Winternitz J. Advances in the Evolutionary Understanding of MHC Polymorphism. Trends in genetics. 2020;36(4):298-311.Proteins encoded by the classical major histocompatibility complex (MHC) genes incite the vertebrate adaptive immune response by presenting peptide antigens on the cell surface. Here, we review mechanisms explaining landmark features of these genes: extreme polymorphism, excess of nonsynonymous changes in peptide-binding domains, and long gene genealogies. Recent studies provide evidence that these features may arise due to pathogens evolving ways to evade immune response guided by the locally common MHC alleles. However, complexities of selection on MHC genes are simultaneously being revealed that need to be incorporated into existing theory. These include pathogen-driven selection for antigen-binding breadth and expansion of the MHC gene family, associated autoimmunity trade-offs, hitchhiking of deleterious mutations linked to the MHC, geographic subdivision, and adaptive introgression. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved

Predictors of job satisfaction among pharmacists: A regional workforce survey

Background: Job satisfaction affects organizational outcomes including performance and retention. The pharmacy job satisfaction literature points to several predictors of job satisfaction, but educational debt and various work settings have not been previously examined. Objectives: To identify predictors of Virginia pharmacists\u27 job satisfaction. Methods: This cross-sectional study used data from the 2018 Virginia Pharmacist Workforce Survey. Of 15,424 registered pharmacists, 13,962 (90.5%) completed the survey. Pharmacists who reported being employed and working in Virginia in the previous year (2017) were included in the analysis (n = 6042). Data were summarized using descriptive statistics. Multiple logistic regression identified predictors of job satisfaction. Results: Respondents were primarily female (66.3%), Pharm.D. degree holders (65.5%), with a 14.8-year average work experience. Most pharmacists (86%) reported being very/somewhat satisfied with their job. Educational debt was not significantly associated with job satisfaction. Significant predictors of job satisfaction included: being female (aOR = 1.28, 95% CI 1.08, 1.52); working \u3c30 (aOR = 1.80, 95% CI 1.14, 2.84), 30–39 (aOR = 1.47, 95% CI 1.02, 2.11), or 40–49 (aOR = 1.42, 95% CI 1.02, 1.98) versus ≥50 h per week; earning an annual income of \u3c$50,000 (aOR = 0.60, 95$150,000 (aOR = 2.05, 95% CI 1.30, 3.23) versus $100,000–$149,999; working in an independent community pharmacy (aOR = 3.72, 95% CI 2.54, 5.44), health system (aOR = 3.81, 95% CI 2.78, 5.22), clinic-based pharmacy (aOR = 4.39, 95% CI 2.18, 8.83), academia (aOR = 5.20, 95% CI 1.97, 13.73), benefits administration (aOR = 3.64, 95% CI 1.71, 7.74), long-term home and home health/infusion (aOR = 1.71, 95% CI 1.10, 2.67), mass merchandiser community (aOR = 0.79, 95% CI 0.62, 0.99), or manufacturer and wholesale distributor (aOR = 3.46, 95% CI 1.97, 6.08) versus chain community pharmacy. Conclusions: Overall, Virginia pharmacists reported high job satisfaction. Pharmacists working in chain community pharmacy reported lower satisfaction relative to other settings. Being female, having a high annual income, and working for less hours was associated with improved job satisfaction

Lymphocyte subtype dysregulation in a group of children with simple obesity

Background: Obesity as a global public health problem is increasing in prevalence. Reports showed that obese children are more liable to infection than lean ones; it was claimed that obese subjects have altered peripheral blood total lymphocyte counts in addition to reduced lymphocyte proliferative response to mitogen stimulation as well as dysregulated cytokine expression.Objective: This study aimed to evaluate the effect of childhood obesity on cell mediated immunity as indicated by peripheral blood lymphocyte phenotyping.Methods: We enrolled 30 school-aged children (mean age 10±3.27 years). They comprised two groups; 20 obese children with a mean body mass index (BMI) of 39.2± 12.5 and 10 matched control subjects with mean BMI of 18.4± 1.9. They were subjected to detailed anthropometric evaluation including weight, height, and waist hip ratio in addition to calculation of BMI, complete blood counting, and flow cytometric assessment of T-helper (CD4), T-cytotoxic/suppressor (CD8), and natural killer (CD56) cell counts .Results: The absolute lymphocyte (CD3) and natural killer cell (CD56) counts were comparable in both groups. However, the CD4%, CD8%, CD4/CD8 ratio were significantly lower in the obese children (p=0.02, 0.03, 0.015 respectively). A significant negative correlation could be elicited between the CD4 count and bodyweight, BMI, and hip waist ratio (p = 0.00); the same was observed for CD4/CD8 ratio (p = 0.00). On the contrary, CD8 correlated positively to the bodyweight, BMI, and waist hip ratio (p = 0.00 for each) .Conclusion: Obesity has an impact on lymphocytic subset counts and further studies are needed to assess its effect on their function.Keywords: obesity, children immunology; CD markers; lymphocytes; BM

How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue

Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disorder of motile cilia dysfunction generally inherited as an autosomal recessive disease. Genetic testing is increasingly considered an early step in the PCD diagnostic workflow. We used targeted panel next generation sequencing (NGS) for genetic screening of 33 Egyptian families with highly clinically suspected PCD. All variants prioritized were Sanger confirmed in the affected individuals and correctly segregated within the family. Targeted NGS yielded a high diagnostic output (70%) with bi‐allelic mutations identified in known PCD genes. Mutations were identified in 13 genes overall, with CCDC40 and CCDC39 the most frequently mutated genes among Egyptian patients. Most identified mutations were predicted null effect variants (79%) and not reported before (85%). This study reveals that the genetic landscape of PCD among Egyptians is highly heterogeneous, indicating that a targeted NGS approach covering multiple genes will provide a superior diagnostic yield than Sanger sequencing for genetic diagnosis. The high diagnostic output achieved here highlights the potential of placing genetic testing early within the diagnostic workflow for PCD, in particular in developing countries where other diagnostic tests can be less available