The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian
species mosquitos highlights a need to monitor the risk of reestablishment of urban ...YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
In Caenorhabditis elegans, the piRNA (21U RNA) pathway is required to establish proper gene regulation and an immortal germline. To achieve this, PRG‐1‐bound 21U RNAs trigger silencing mechanisms ...mediated by RNA‐dependent RNA polymerase (RdRP)‐synthetized 22G RNAs. This silencing can become PRG‐1‐independent and heritable over many generations, a state termed RNA‐induced epigenetic gene silencing (RNAe). How and when RNAe is established, and how it is maintained, is not known. We show that maternally provided 21U RNAs can be sufficient for triggering RNAe in embryos. Additionally, we identify PID‐2, a protein containing intrinsically disordered regions (IDRs), as a factor required for establishing and maintaining RNAe. PID‐2 interacts with two newly identified and partially redundant eTudor domain‐containing proteins, PID‐4 and PID‐5. PID‐5 has an additional domain related to the X‐prolyl aminopeptidase APP‐1, and binds APP‐1, implicating potential N‐terminal proteolysis in RNAe. All three proteins are required for germline immortality, localize to perinuclear foci, affect size and appearance of RNA inheritance‐linked Z granules, and are required for balancing of 22G RNA populations. Overall, our study identifies three new proteins with crucial functions in C. elegans small RNA silencing.
SYNOPSIS
Caenorhabditis elegans maternal piRNAs are sufficient to establish and maintain stable epigenetic silencing without further piRNA production (termed RNAe). Here, PID‐2 and its newly‐found interactors PID‐4 and PID‐5, are shown to be required for this heritable silencing, in addition to affecting Z granule homeostasis.
Maternal piRNAs are sufficient to trigger long‐term multigenerational silencing in embryos.
Intrinsically‐disordered protein PID‐2 is required for effective piRNA‐induced silencing, and interacts with Tudor‐domain proteins PID‐4 and PID‐5.
PID‐2, PID‐4 and PID‐5 are required for efficient inheritance of silencing and maintenance of germline function/germline immortality across generations.
PID‐2, PID‐4 and PID‐5 localize to perinuclear foci and modulate size and appearance of RNA inheritance‐linked Z granules, balancing 22G RNA populations.
PID‐2 and its newly‐identified interactors PID‐4 and PID‐5 modulate size and appearance of Z granules to establish and maintain stable heritable silencing (RNAe) by maternal piRNAs.
The Piwi-piRNA pathway represents a germline-specific transposon-defense system. C. elegans Piwi, prg-1, is a non-essential gene and triggers a secondary RNAi response that depends on mutator genes, ...endo-siRNAs (22G-RNAs), and the 22G-RNA-binding Argonaute protein HRDE-1. Interestingly, silencing of PRG-1 targets can become PRG-1 independent. This state, known as RNAe, is heritable and depends on mutator genes and HRDE-1. We studied how the transgenerational memory of RNAe and the piRNA pathway interact. We find that maternally provided PRG-1 is required for de novo establishment of 22G-RNA populations, especially those targeting transposons. Strikingly, attempts to re-establish 22G-RNAs in absence of both PRG-1 and RNAe memory result in severe germline proliferation defects. This is accompanied by a disturbed balance between gene-activating and -repressing 22G-RNA pathways. We propose a model in which CSR-1 prevents the loading of HRDE-1 and in which both PRG-1 and HRDE-1 help to keep mutator activity focused on the proper targets.
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•Maternal 21U RNAs are required to start de novo transposon silencing in C. elegans•PRG-1, HRDE-1, and WAGO-1/WAGO-2/WAGO-3 coordinate silencing of Tc1 transposition•Mutators drive silencing of germline genes in absence of parental 21U and 22G RNA•CDE-1-mediated 22G RNA turnover prevents silencing of germline genes by HRDE-1
de Albuquerque et al. demonstrate that in C. elegans, transgenerational memory of piRNAs and endogenous siRNAs is required for proper germ cell development. Without this memory, the silencing machinery cannot properly silence transposons and, in addition, starts to act on genes that should be expressed.
In animal husbandry, antimicrobial agents have been administered as supplements to increase production over the last 60 years. Large-scale animal production has increased the importance of antibiotic ...management because it may favor the evolution of antimicrobial resistance and select resistant strains. Brazil is a significant producer and exporter of animal-derived food. Although Brazil is still preparing a national surveillance plan, several changes in legislation and timely programs have been implemented. Thus, Brazilian data on antimicrobial resistance in bacteria associated with animals come from official programs and the scientific community. This review aims to update and discuss the available Brazilian data on this topic, emphasizing legal aspects, incidence, and genetics of the resistance reported by studies published since 2009, focusing on farm animals and derived foods with the most global public health impact. Studies are related to poultry, cattle, and pigs, and mainly concentrate on non-typhoid
,
, and
. We also describe legal aspects of antimicrobial use in this context; and the current occurrence of genetic elements associated with resistance to beta-lactams, colistin, and fluoroquinolones, among other antimicrobial agents. Data here presented may be useful to provide a better understanding of the Brazilian status on antimicrobial resistance related to farm animals and animal-derived food products.
The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies ...(GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained \ 2.41 M SNPs for SC, PWG, and YW and \ 5.06 M SNPs for AFC. Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.
Type 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia ...leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.
piRNAs play a critical role in the regulation of transposons and other germline genes. In
, regulation of piRNA target genes is mediated by the
complex, which synthesizes high levels of siRNAs ...through the activity of an RNA-dependent RNA polymerase. However, the steps between mRNA recognition by the piRNA pathway and siRNA amplification by the
complex are unknown. Here, we identify the Tudor domain protein, SIMR-1, as acting downstream of piRNA production and upstream of
complex-dependent siRNA biogenesis. Interestingly, SIMR-1 also localizes to distinct subcellular foci adjacent to P granules and
foci, two phase-separated condensates that are the sites of piRNA-dependent mRNA recognition and
complex-dependent siRNA amplification, respectively. Thus, our data suggests a role for multiple perinuclear condensates in organizing the piRNA pathway and promoting mRNA regulation by the
complex.
Purpose
Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive ...computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms.
Methods
Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS.
Results
Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster.
Conclusion
The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.
Genomic selection (GS) offers a promising opportunity for selecting more efficient animals to use consumed energy for maintenance and growth functions, impacting profitability and environmental ...sustainability. Here, we compared the prediction accuracy of multi-layer neural network (MLNN) and support vector regression (SVR) against single-trait (STGBLUP), multi-trait genomic best linear unbiased prediction (MTGBLUP), and Bayesian regression (BayesA, BayesB, BayesC, BRR, and BLasso) for feed efficiency (FE) traits. FE-related traits were measured in 1156 Nellore cattle from an experimental breeding program genotyped for ~ 300 K markers after quality control. Prediction accuracy (Acc) was evaluated using a forward validation splitting the dataset based on birth year, considering the phenotypes adjusted for the fixed effects and covariates as pseudo-phenotypes. The MLNN and SVR approaches were trained by randomly splitting the training population into fivefold to select the best hyperparameters. The results show that the machine learning methods (MLNN and SVR) and MTGBLUP outperformed STGBLUP and the Bayesian regression approaches, increasing the Acc by approximately 8.9%, 14.6%, and 13.7% using MLNN, SVR, and MTGBLUP, respectively. Acc for SVR and MTGBLUP were slightly different, ranging from 0.62 to 0.69 and 0.62 to 0.68, respectively, with empirically unbiased for both models (0.97 and 1.09). Our results indicated that SVR and MTGBLUBP approaches were more accurate in predicting FE-related traits than Bayesian regression and STGBLUP and seemed competitive for GS of complex phenotypes with various degrees of inheritance.
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