Integrating Genetic and Genomic Analyses of Combined Health Data Across Ecotypes to Improve Disease Resistance in Indigenous African Chickens.

Poultry play an important role in the agriculture of many African countries. The majority of chickens in sub-Saharan Africa are indigenous, raised in villages under semi-scavenging conditions. Vaccinations and biosecurity measures rarely apply, and infectious diseases remain a major cause of mortality and reduced productivity. Genomic selection for disease resistance offers a potentially sustainable solution but this requires sufficient numbers of individual birds with genomic and phenotypic data, which is often a challenge to collect in the small populations of indigenous chicken ecotypes. The use of information across-ecotypes presents an attractive possibility to increase the relevant numbers and the accuracy of genomic selection. In this study, we performed a joint analysis of two distinct Ethiopian indigenous chicken ecotypes to investigate the genomic architecture of important health and productivity traits and explore the feasibility of conducting genomic selection across-ecotype. Phenotypic traits considered were antibody response to Infectious Bursal Disease (IBDV), Marek's Disease (MDV), Fowl Cholera (PM) and Fowl Typhoid (SG), resistance to Eimeria and cestode parasitism, and productivity [body weight and body condition score (BCS)]. Combined data from the two chicken ecotypes, Horro (n = 384) and Jarso (n = 376), were jointly analyzed for genetic parameter estimation, genome-wide association studies (GWAS), genomic breeding value (GEBVs) calculation, genomic predictions, whole-genome sequencing (WGS), and pathways analyses. Estimates of across-ecotype heritability were significant and moderate in magnitude (0.22-0.47) for all traits except for SG and BCS. GWAS identified several significant genomic associations with health and productivity traits. The WGS analysis revealed putative candidate genes and mutations for IBDV (TOLLIP, ANGPTL5, BCL9, THEMIS2), MDV (GRM7), SG (MAP3K21), Eimeria (TOM1L1) and cestodes (TNFAIP1, ATG9A, NOS2) parasitism, which warrant further investigation. Reliability of GEBVs increased compared to within-ecotype calculations but accuracy of genomic prediction did not, probably because the genetic distance between the two ecotypes offset the benefit from increased sample size. However, for some traits genomic prediction was only feasible in across-ecotype analysis. Our results generally underpin the potential of genomic selection to enhance health and productivity across-ecotypes. Future studies should establish the required minimum sample size and genetic similarity between ecotypes to ensure accurate joint genomic selection.

GST-4-Dependent Suppression of Neurodegeneration in C. elegans Models of Parkinson's and Machado-Joseph Disease by Rapeseed Pomace Extract Supplementation.

Genetic mutations and aging-associated oxidative damage underlie the onset and progression of neurodegenerative diseases, like Parkinson's disease (PD) and Machado-Joseph disease (MJD). Natural products derived from plants have been regarded as important sources of novel bioactive compounds to counteract neurodegeneration. Here, we tested the neuroprotective effect of an ethanolic extract of rapeseed pomace (RSP), a rapeseed (canola) oil production by-product, in C. elegans models of MJD and PD. The extract, containing sinapine and other phenolics, restored motor function of mutant ataxin-3 (ATXN3) animals (MJD) and prevented degeneration of dopaminergic neurons in one toxin-induced and two genetic models of PD. Whole-organism sensors of antioxidant and xenobiotic response activation revealed the induction of phase II detoxification enzymes, including glutathione S- transferase (GST-4) upon RSP extract supplementation. Furthermore in vivo pharmacogenetic studies confirmed gst-4 is required for the therapeutic effect of RSP extract in the two disease models. The results suggest that GST-4-mediated antioxidant pathways may constitute promising therapeutic co-targets for neurodegenerative diseases and confirm the utility of searching for bioactive compounds in novel sources, including food and agricultural waste/by-products, such as RSP.

Naloxone interventions in opioid overdoses: a systematic review protocol.

BACKGROUND: North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. METHODS: To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies. DISCUSSION: Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs.