Miracle-dz/UniFAR-FTUs huggingface dataset:
Feedlot Cattle Antimicrobial Use Surveillance Network: A Canadian Journey

Antimicrobial drugs are important tools for maintaining human and animal health. Globally, antimicrobial use (AMU) in food-producing animals is under increasing scrutiny due to its potential to promote antimicrobial resistance (AMR). Historically, comprehensive Canadian data related to the types of antimicrobial drugs used, extent of use, common indicators of use and the demographics of the cattle populations receiving antimicrobial drugs have been limited, in part due to segmentation in the cattle industry and fragmentation of the drug distribution system. Appropriate AMU estimates are required to understand AMU practices, to interpret AMR levels and patterns, to meaningfully assess associated public health risks, and to inform stewardship activities. The Canadian beef cattle industry has a long history of collaboration in AMU and AMR research. Prior research projects identified both opportunities and challenges in the collection of AMU data. Cornerstone projects provided insight into the complexity of collecting AMU data in Canada's feedlot sector. This paper will discuss how the lessons learned from past work have contributed to the formation of a Canadian fed-cattle antimicrobial surveillance program that was initiated in 2019. This important surveillance program will allow feedlot cattle AMU to improve management decisions and support AMU best practices in the evolving Canadian AMR landscape.
Mathematical Quantification of Transmission in Experiments: FMDV Transmission in Pigs Can Be Blocked by Vaccination and Separation

Quantitative understanding of transmission with and without control measures is important for the control of infectious diseases because it helps to determine which of these measures (or combinations thereof) will be effective to reduce transmission. In this paper, the statistical methods used to estimate transmission parameters are explained. To show how these methods can be used we reviewed literature for papers describing foot-and-mouth disease virus (FMDV) transmission in pigs and we used the data to estimate transmission parameters. The analysis showed that FMDV transmits very well when pigs have direct contact. Transmission, however, is reduced when a physical barrier separates infected and susceptible non-vaccinated pigs. Vaccination of pigs can prevent infection when virus is administered by a single intradermal virus injection in the bulb of the heel, but it cannot prevent infection when pigs are directly exposed to either non-vaccinated or vaccinated FMDV infected pigs. Physical separation combined with vaccination is observed to block transmission. Vaccination and separation can make a significant difference in the estimated number of new infections per day. Experimental transmission studies show that the combined effect of vaccination and physical separation can significantly reduce transmission (R < 1), which is a very relevant result for the control of between-farm transmission.
Temperature Effect on Traditional Pear (Pyrus communis L.) Landraces Seed Germination

Author SJ designed the study, carried out the laboratory research, contributed with the applied laboratory methodology for the method and temperatures of seed stratification according to the previous research, analyzed the obtained results, literature searches and manuscript writing and is corresponded author respectively. Author EMM performed the statistical analysis of data, manuscript writing and complemented to the literature searches. Both authors read and approved the final manuscript. ABSTRACT Investigations included six traditional pear landraces ( Pyrus communis L.): Aleksandra, Vodenka, Patlidjanka, Ljubichica, Tatlikuti and Crvenushk a . The number of seeds per fruit, seed energy and total seed germination were investigated and statistically analysed ( P = .05 and P = .01). Seed stratification encompassed pre-chilling by using three treatments: I treatment covers seed pre-chilling at -18°C for 24 hours; II treatment covers seed pre-chilling at +1°C for 2 weeks; III treatment covers seed pre-chilling at +8°C for 1 week. Only Patlidjanka belongs to the group with high seed number in the fruit. The other landraces produced low seed number like 2-3 seeds per fruit. The average number of all researched landraces is 3.67 seeds per fruit. The pear Tatlikuti showed a very high significant difference ( P = .01). It was concluded that III treatment showed the highest seed energy at landraces Ljubichica 77.5% and Tatlikuti 75.0% and the lowest at Aleksandra 52.5%. There were significant differences ( P = .05) between the applied treatments regarding seed energy. In II treatment, the total seed germination had the highest effect on Patlidjanka 87.75%. The values for germination seeds in the other landraces were in the range of 77.5% to 86.25%. Statistically, a significant difference was determined in the landraces Ljubichica and Crvenushka ( P = .05), and there was high significant difference ( P = .01) in the pear Aleksandra. The II and III treatments could be recommended as the most suitable to improve the pear seed germination.
Mapping of Quantitative Trait Loci for Growth and Carcass-Related Traits in Chickens Using a Restriction-Site Associated DNA Sequencing Method

In the present study, quantitative trait loci (QTLs) analysis was performed to identify the chromosomal positions of growth and carcass-related trait QTLs using 319 F2 chickens obtained from intercrosses of an Oh-Shamo male and four White Plymouth Rock females. Body weight was measured weekly until the birds were 7 weeks old. Carcass-related traits were also measured at this timepoint. A genetic linkage map was constructed using 545 single nucleotide polymorphism (SNP) markers that were developed using a restriction-site associated DNA sequencing method. The linkage map included the 23 autosomes and the Z chromosome. Using simple interval QTL mapping, we were able to identify 10 significant and suggestive main-effect QTLs for growth and carcass-related traits present on chromosomes 1, 2, 3, 5, 8, 19, 24, and Z. These loci explained 5.60–16.52% of the phenotypic variances. The chromosomal positions of the 10 QTLs overlapped with those of previously reported QTLs, whereas the targeted traits varied. Our QTLs will aid future breeding programs in improving growth and meat yield of chickens (e.g., via marker-assisted selection), particularly in the Japanese brand chicken industry.
The Interplay of Host Lysosomes and Intracellular Pathogens

Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as Mycobacterium tuberculosis (Mtb) and Salmonella avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking. In this review, the mechanisms by which the respective pathogen containing vacuoles (PCVs) intersect with lysosomal trafficking pathways and maintain their distinctness are discussed. Despite such active inhibition of lysosomal targeting, emerging literature shows that different pathogens or pathogen derived products exhibit a global influence on the host lysosomal system. Pathogen mediated lysosomal enrichment promotes the trafficking of a sub-set of pathogens to lysosomes, indicating heterogeneity in the host-pathogen encounter. This review integrates recent advancements on the global lysosomal alterations upon infections and the host protective role of the lysosomes against these pathogens. The review also briefly discusses the heterogeneity in the lysosomal targeting of these pathogens and the possible mechanisms and consequences.
Morphology, Multilocus Phylogeny, and Toxin Analysis Reveal Amanita albolimbata, the First Lethal Amanita Species From Benin, West Africa

Many species of Amanita sect. Phalloideae (Fr.) Quél. cause death of people after consumption around the world. Amanita albolimbata, a new species of A. sect. Phalloideae from Benin, is described here. The taxon represents the first lethal species of A. sect. Phalloideae known from Benin. Morphology and molecular phylogenetic analyses based on five genes (ITS, nrLSU, rpb2, tef1-α, and β-tubulin) revealed that A. albolimbata is a distinct species. The species is characterized by its smooth, white pileus sometimes covered by a patchy volval remnant, a bulbous stipe with a white limbate volva, broadly ellipsoid to ellipsoid, amyloid basidiospores, and abundant inflated cells in the volva. Screening for the most notorious toxins by liquid chromatography–high-resolution mass spectrometry revealed the presence of α-amanitin, β-amanitin, and phallacidin in A. albolimbata.
Massively parallel phenotyping of variant impact in cancer with Perturb-seq reveals a shift in the spectrum of cell states induced by somatic mutations

Genome sequencing studies have identified millions of somatic variants in cancer, but their phenotypic impact remains challenging to predict. Current experimental approaches to distinguish between functionally impactful and neutral variants require customized phenotypic assays that often report on average effects, and are not easily scaled. Here, we develop a generalizable, high-dimensional, and scalable approach to functionally assess variant impact in single cells by pooled Perturb-seq. Specifically, we assessed the impact of 200 TP53 and KRAS variants in >300,000 single lung cancer cells, and used the profiles to categorize variants into phenotypic subsets to distinguish gain-of-function, loss-of-function and dominant negative variants, which we validated by comparison to orthogonal assays. Surprisingly, KRAS variants did not merely fit into discrete functional categories, but rather spanned a continuum of gain-of-function phenotypes driven by quantitative shifts in cell composition at the single cell level. We further discovered novel gain-of-function KRAS variants whose impact could not have been predicted solely by their occurrence in patient samples. Our work provides a scalable, gene-agnostic method for coding variant impact phenotyping, which can be applied in cancer and other diseases driven by somatic or germline coding mutations.
A piggyBac-based toolkit for inducible genome editing in mammalian cells

We describe the development and application of a novel series of vectors that facilitate CRISPR-Cas9-mediated genome editing in mammalian cells, which we call CRISPR-Bac. CRISPR-Bac leverages the piggyBac transposon to randomly insert CRISPR-Cas9 components into mammalian genomes. In CRISPR-Bac, a single piggyBac cargo vector containing a doxycycline-inducible Cas9 or catalytically-dead Cas9 (dCas9) variant and a gene conferring resistance to Hygromycin B is co-transfected with a plasmid expressing the piggyBac transposase. A second cargo vector, expressing a single-guide RNA (sgRNA) of interest, the reverse-tetracycline TransActivator (rtTA), and a gene conferring resistance to G418, is also cotransfected. Subsequent selection on Hygromycin B and G418 generates polyclonal cell populations that stably express Cas9, rtTA, and the sgRNA(s) of interest. Using Mus musculus-derived embryonic and trophoblast stem cells, we show that CRISPR-Bac can be used to knockdown proteins of interest, to create targeted genetic deletions with high efficiency, and to activate or repress transcription of protein-coding genes and an imprinted long noncoding RNA. The ratio of sgRNA-to-Cas9-to-transposase can be adjusted in transfections to alter the average number of cargo insertions into the genome. sgRNAs targeting multiple genes can be inserted in a single transfection. CRISPR-Bac is a versatile platform for genome editing that simplifies the generation of mammalian cells that stably express the CRISPR-Cas9 machinery.
Recovering genomes and phenotypes using allele-specific gene expression

With the recent increase in RNA sequencing efforts using large cohorts of individuals, studying allele-specific gene expression is becoming increasingly important. Here, we report that, despite not containing explicit variant information, a list of allele-specific gene names of an individual is enough to recover key variants and link the individual back to their genome or phenotype. This creates a privacy conundrum.
Methyltransferase SMYD5 Exaggerates IBD by Downregulating Mitochondrial Functions via Post-translational Control of PGC-1α Stability

Background and Aims The expression and role of methyltransferase SET and MYND domain-containing protein 5 (SMYD5) in inflammatory bowel diseases (IBD) is completely unknown. Here, we investigated the role and the underlying mechanism of epithelial SMYD5 in IBD pathogenesis and progression. Methods The expression and subcellular localization of SMYD5 and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) were examined by Western blot analysis, immunofluorescence staining, and immunohistochemistry in intestinal epithelial cells (IECs) and in colon tissues from human IBD patients and mice with experimental colitis. Mice with Smyd5 conditional knockout in IECs and littermate controls were subjected to DSS-induced experimental colitis and the disease severity and inflammation were assessed. SMYD5-regulated mitochondrial biogenesis was examined by RT-qPCR and transmission electron microscopy and mitochondrial oxygen consumption rate was measured in a Seahorse Analyzer system. The interaction between SMYD5 and PGC-1α was determined by co-immunoprecipitation assay. PGC-1α degradation and turnover (half-life) were analyzed by cycloheximide chase assay. SMYD5-mediated PGC-1α methylation was measured via in vitro methylation followed by mass spectrometry to identify the specific lysine residues that were methylated. Results Up-regulated SMYD5 and down-regulated PGC-1α were observed in IECs from IBD patients and mice with experimental colitis. However, Smyd5 depletion in IECs protected mice from DSS-induced colitis. SMYD5 was critically involved in regulating mitochondrial biology such as mitochondrial biogenesis, respiration, and apoptosis. Mechanistically, SMYD5 regulated mitochondrial functions in a PGC-1α dependent manner. Further, SMYD5 mediated lysine methylation of PGC-1α and facilitated its ubiquitination and proteasomal degradation. Conclusion SMYD5 attenuates mitochondrial functions in IECs and promotes IBD progression by enhancing the proteasome-mediated degradation of PGC-1α protein in methylation-dependent manner. Strategies to decrease SMYD5 expression and/or increase PGC-1α expression in IECs might be a promising therapeutic approach to treat patients with IBD.
The C. elegans homolog of TMEM132D, a human panic-disorder and anxiety risk gene, modulates neuronal morphogenesis through the WAVE-regulatory complex

TMEM132D is a human gene identified with multiple risk alleles for panic disorders, anxiety and major depressive disorders. Belonging to a conserved family of transmembrane proteins, TMEM132D and its homologs are still of unknown molecular functions. By generating loss-of-function mutants of the sole TMEM132 ortholog in C. elegans, we identify abnormal morphologic phenotypes in the dopaminergic PDE neurons. Using a yeast two-hybrid screen, we find that NAP1 directly interacts with the cytoplasmic domain of human TMEM132D, and mutations in C. elegans tmem-132 that disrupt the interaction with NAP1 cause similar morphologic defects in the PDE neurons. NAP1 is a component of the WAVE regulatory complex (WRC) that controls F-actin cytoskeletal dynamics. Decreasing activity of WRC rescues the PDE defects in tmem-132 mutants, whereas gain-of-function of TMEM132D in mammalian cells inhibits WRC, leading to decreased abundance of selective WRC components, impaired actin nucleation and cell motility. We propose that metazoan TMEM132 family proteins play evolutionarily conserved roles in regulating NAP1 protein homologs to restrict inappropriate WRC activity, cytoskeletal and morphologic changes in the cell.
Effect of Exercise Training and Vitamins E and C on Antioxidant Enzyme Activities and Lipid Peroxidation in Aging Rats

Background: There are many conditions that may affect the antioxidant enzyme activities, as aging and exercise. Moderate regular exercise up-regulate activities of antioxidant enzymes with depressant action on the lipid peroxidation processes, while strenuous exercise have a depressant effect on the activities of antioxidant enzymes with stimulatory action on the lipid peroxidation processes. Glutathione-S transferase (GST) and catalase are the major part of the specific antioxidant enzyme defence system response; malondialdehyde is the major indicator to lipid peroxidation processes which are affected by the exercise. Aim of the work: To study the effect of moderate regular exercise and strenuous exercise with and without vitamin E or C supplementation on antioxidant defence system. Material and Methods: Fifty six aging male albino rats were used in the present experiment. They were equally divided into seven groups. Group I: control group, Group II: moderate regular exercised group. Group III: strenuous exercised group. Group IV: moderate regular exercised group with vitamin E supplementation. Group V: strenuous exercised group with vitamin E supplementation, Group VI: moderate regular exercised group with vitamin C supplementation. Group VII: strenuous exercised group with vitamin C supplementation. The exercise was performed on a modified manual treadmill and the experiment continued for two months. Peripheral blood samples and muscular tissue samples were taken from all animal groups for estimation of glutathione-S transferase, catalase and malondialdehyde. Results: The moderate regular exercise with or without vitamin E or C supplementation increased the antioxidant enzymes Glutathione-S transferase, catalase and decreased the malondialdehyde in serum and muscular tissue. The strenuous exercise decrease the antioxidant enzymes and increase the malondialdehyde production, while with vitamin E or C supplementation strenuous exercise enhanced the antioxidant enzymes and decreased the malondialdehyde production. Conclusion: The moderate regular exercise enhance the antioxidant defence system and so inhibit the lipid peroxidation production, while the strenuous exercise inhibit the antioxidant defence system activity and increase the lipid peroxidation production. Supplementation with vitamin E or C is essential to enhance the antioxidant defence system activities that decrease lipid peroxidation.
Multi-Modal Profiling of Human Fetal Liver-Derived Hematopoietic Stem Cells Reveals the Molecular Signature of Engraftment Potential

The human hematopoietic stem cell (HSC) harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, HSCs in the fetal liver (FL) undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. We profiled 26,407 FL cells at both transcriptional and protein levels including over 7,000 highly enriched and functional FL HSCs to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression revealed a generalizable signature defining functional FL HSCs and allowed for the stratification of enrichment strategies with high translational potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers, serving as a useful resource for the field.
dmrff: identifying differentially methylated regions efficiently with power and control

A differentially methylated region (DMR) is a genomic region in which DNA methylation is consistently positively or negatively associated with a phenotype or exposure. We demonstrate that existing algorithms for identifying DMRs either fail to consistently control false positive rates (comb-p and DMRcate), suffer from low power (bumphunter) or lack modeling flexibility (seqlm). We introduce a new method, dmrff, that overcomes these shortcomings and can additionally be used to meta-analyze multiple datasets. When applied to investigate associations of age in multiple datasets, dmrff identifies novel DMRs near genes previously linked to age. An R implementation is available on Github (http://github.com/perishky/dmrff).
Structure and variability of optogenetic responses identify the operating regime of cortex

Predicting the response of the cortical microcircuit to perturbations is a prerequisite to determine the mechanisms that mediate its response to stimulus; yet, an encompassing perspective that describes the full ensemble of the network’s response in models that accurately recapitulate recorded data is still lacking. Here we develop a class of mathematically tractable models that exactly describe the modulation of the distribution of cell-type-specific calcium-imaging activity with the contrast of a visual stimulus. The inferred parameters recover signatures of the connectivity structure found in mouse visual cortex. Analysis of this structure subsequently reveals parameter-independent relations between the responses of different cell types to perturbations and each interneuron’s role in circuit-stabilization. Leveraging recent theoretical approaches, we derive explicit expressions for the distribution of responses to partial perturbations which reveal a novel, counter intuitive effect in the sign of response functions. Finally applying the theory to inferring feedback to V1 during locomotion, we find that it is predominantly mediated by both SOM and VIP modulation.
Coach Education and Positive Youth Development as a Means of Improving Australian Sport

1 School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, QLD, Australia, Department of Sport, Hartpury University, Hartpury, United Kingdom, 3 School of Health and Behavioural Sciences, University of the Sunshine Coast, Sunshine Coast, QLD, Australia, 4 School of Health, Medical and Applied Sciences, Appleton Institute for Behavioural Science, Central Queensland University, Adelaide, SA, Australia