Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic characterization of AmpC and extended-spectrum beta-lactamase (ESBL) phenotypes in Escherichia coli and Salmonella from Alberta poultry

Horizontal gene transfer is an important mechanism which facilitates bacterial populations in overcoming antimicrobial treatment. In this study, a total of 120 Escherichia coli and 62 Salmonella enterica subsp. enterica isolates were isolated from poultry farms in Alberta. Fourteen serovars were identified among Salmonella isolates. Thirty one percent of E. coli isolates were multiclass drug resistant (resistant to ≥ 3 drug classes), while only about 16% of Salmonella isolates were multiclass drug resistant. Among those, eight E. coli isolates had an AmpC-type phenotype, and one Salmonella isolate had an extended-spectrum beta-lactamase (ESBL)-type β-lactamase phenotype. We identified both AmpC-type (blaCMY-2) and ESBL-type (blaTEM) genes in both E. coli and Salmonella isolates. Plasmids from eight of nine E. coli and Salmonella isolates were transferred to recipient strain E. coli J53 through conjugation. Transferable plasmids in above total eight E. coli and Salmonella isolates were also transferred into a lab-made sodium azide-resistant Salmonella recipient through conjugation. The class 1 integrase gene, int1, was detected on plasmids from two E. coli isolates. Further investigation of class 1 integron cassette regions revealed the presence of an aadA gene encoding streptomycin 3”-adenylyltransferase, an aadA1a/aadA2 gene encoding aminoglycoside 3”-O-adenyltransferase, and a putative adenylyltransferase gene. This study provides some insight into potential horizontal gene transfer events of antimicrobial resistance genes between E. coli and Salmonella in poultry production.
Complex plant metabolomes guide fitness-relevant foraging decisions of a specialist herbivore

Plants produce complex mixtures of primary and secondary metabolites. Herbivores use these metabolites as behavioral cues to increase their fitness. However, how herbivores integrate different metabolite classes into fitness-relevant foraging decisions in planta is poorly understood. We developed a molecular manipulative approach to modulate the availability of sugars and benzoxazinoid secondary metabolites as foraging cues for a specialist maize herbivore, the western corn rootworm. By disrupting sugar perception in the western corn rootworm and benzoxazinoid production in maize, we show that sugars and benzoxazinoids act as distinct and dynamically integrated mediators of short-distance host finding and acceptance. While sugars improve the capacity of rootworm larvae to find a host plant and to distinguish post-embryonic from less nutritious embryonic roots, benzoxazinoids are specifically required for the latter. Host acceptance in the form of root damage is increased by benzoxazinoids and sugars in an additive manner. This pattern is driven by increasing damage to post-embryonic roots in the presence of benzoxazinoids and sugars. Benzoxazinoid- and sugar-mediated foraging directly improves western corn rootworm growth and survival. Interestingly, western corn rootworm larvae retain a substantial fraction of their capacity to feed and survive on maize plants even when both classes of chemical cues are almost completely absent. This study unravels fine-grained differentiation and integration of primary and secondary metabolites into herbivore foraging and documents how the capacity to compensate for the lack of important chemical cues enables a specialist herbivore to survive within unpredictable metabolic landscapes.
Emergent properties of a mitotic Kif18b-MCAK-EB network

The precise regulation of microtubule length during mitosis is essential to assemble and position the mitotic spindle and segregate chromosomes. Prior work has identified key molecular players in this process, including the kinesin-18 Kif18b and the kinesin-13 Kif2C/MCAK, which both promote microtubule depolymerization. MCAK acts as a potent microtubule depolymerase diffusing short distances on microtubules, while Kif18b is a mitotic processive motor with weak depolymerase activity. However the individual activities of these factors cannot explain the dramatic increase in microtubule dynamics in mitosis. Using in vitro reconstitution and single molecule imaging, we demonstrate that Kif18b, MCAK and the plus-end tracking protein EB3 act in an integrated manner to potently promote microtubule depolymerization. We find Kif18b acts as a microtubule plus end delivery factor for its cargo MCAK, and that Kif18b also promotes EB accumulation to plus ends independently of lattice nucleotide state. Together, our work defines the mechanistic basis for a cooperative Kif18b-EB-MCAK network with emergent properties, that acts to efficiently shorten microtubules in mitosis.
The secret of VDAC isoforms is in their gene regulation? Characterization of human VDAC genes expression profile, promoter activity, and transcriptional regulators

Background VDACs (Voltage-Dependent Anion-selective Channels) are pore-forming proteins of the outer mitochondrial membrane, whose permeability is primarily due to their presence. In higher eukaryotes three isoforms raised during the evolution: they have the same exon-intron organization and the proteins show the same channel-forming activity. We provide a comprehensive analysis of the three human VDAC genes (VDAC1–3), their expression profiles, promoter activity, and potential transcriptional regulators. Results VDAC isoforms are broadly but also specifically expressed in various human tissues at different levels with a predominance of VDAC1 and VDAC2 over VDAC3. However, RNA-seq CAGE approach revealed a higher level of transcription activation of VDAC3 gene. We experimentally confirmed this information by reporter assay of VDACs promoter activity. Transcription Factor Binding Sites (TFBSs) distribution in the promoters was investigated. The main regulators common to the three VDAC genes were identified as E2FF, NRF1, KLFS, EBOX transcription factors family members. All of them are involved in cell cycle and growth, proliferation, differentiation, apoptosis, and metabolism. More transcription factors specific for each isoform gene were identified, supporting the results in the literature, indicating a general role of VDAC1, as actor of apoptosis for VDAC2, and the involvement in sex determination and development of VDAC3. Conclusions For the first time, we propose a comparative analysis of human VDAC promoters to investigate their specific biological functions. Bioinformatics and experimental results confirm the essential role of VDAC protein family in mitochondrial functionality. Moreover, insights about a specialized function and different regulation mechanisms arise for the three isoforms genes.
A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer

Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively). Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
De quelques nématodes des garides valaisannes

Dans le dernier Bulletin de la Murithienne (8), le Dr Staeger insistait sur l'intérêt certain qu'il y aurait à étudier systématiquement la microfaune du sol des garides valaisannes. Lors de la course du printemps 1950, j 'ai eu la curiosité de faire deux prélèvements de sol, l'un à 50 m. environ plus bas que l'orée du bois, au haut des coteaux de Branson, sur le chemin de la Jeur Brûlée, l'autre sur l'arête des Follaterres, au bord du sentier d'Alesse, à 900 m. d'altitude. Il ne s'agit pas là, me semble-t-il, de la garide proprement dite. Mais nous n'en sommes pas moins en plein milieu xérothermique, aux écarts de température très sensibles, aux précipitations relativement peu abondantes, à la flore si spéciale qui dénote un milieu spécial, lui aussi. Je n'ai tenu aucun compte des associations végétales, ni de la nature du sol, ne pensant pas que cette première étude m'entraînerait si loin du point de vue de la systématique. Il serait intéressant maintenant de définir, en Valais, un ou plusieurs milieux bien caractéristiques, et de les soumettre à une étude précise et coordonnée. Se trouvera-t-il un groupe de botanistes et de biologistes du sol, pour entreprendre ce travail ? Un seul chercheur ne saurait suffire à tout.
Humanization of Drosophila Gαo to Model GNAO1 Paediatric Encephalopathies

Several hundred genes have been identified to contribute to epilepsy – the disease affecting 65 million people worldwide. One of these genes is GNAO1 encoding Gαo, the major neuronal α-subunit of heterotrimeric G proteins. An avalanche of dominant de novo mutations in GNAO1 have been recently described in paediatric epileptic patients, suffering in addition to epilepsy from motor dysfunction and developmental delay. Although occurring in amino acids conserved from humans to Drosophila, these mutations and their functional consequences have only poorly been analysed at the biochemical or neuronal levels. Adequate animal models to study molecular aetiology of GNAO1 encephalopathies have also so far been lacking. As the first step towards modelling the disease in Drosophila, we here describe humanization of the Gαo locus in the fruit fly. A two-step CRISPR/Cas9-mediated replacement was conducted, first substituting the coding exons 2-3 of Gαo with respective human GNAO1 sequences. At the next step, the remaining exons 4-7 were similarly replaced, keeping intact the gene Cyp49a1 embedded in-between, as well as the non-coding exon 1 and the surrounding regulatory sequences. The resulting flies, homozygous for the humanized GNAO1 loci, are viable and fertile without any visible phenotypes; their body weight and longevity are also normal. Human Gαo-specific antibodies confirm the endogenous-level expression of the humanized Gαo, which fully replaces the Drosophila functions. The genetic model we established will make it easy to incorporate encephalopathic GNAO1 mutations and will permit intensive investigations into the molecular aetiology of the human disease through the powerful toolkit of Drosophila genetics.
Microbiota in milk from healthy and mastitis cows varies greatly in diversity, species richness and composition, as revealed by PacBio sequencing

Mastitis is the most economically important disease of dairy cows. This study used PacBio single-molecule real-time sequencing technology to sequence the full-length of the l6S rRNA from the microbiota in 27 milk samples (18 from mastitis and 9 from healthy cows; the cows were at different stages of lactation). We observed that healthy or late stage milk microbiota had significantly higher microbial diversity and richness. The community composition of the microbiota from different groups also varied greatly. In milk from healthy cows the microbiota was predominantly comprised of Lactococcus lactis, Acinetobacter johnsonii and Bacteroides dorei, while from mastitis cows it was predominantly comprised of Bacillus cereus, Clostridium cadaveris and Streptococcus suis. The prevalence of La. lactis and B. cereus in milk from healthy and mastitis cows was confirmed by digital droplets PCR. Differences in milk microbiota composition could suggest an important role for these microbes in protecting the host from mastitis. Based on the milk microbiota profiles, the Udder Health Index was constructed to predict the risk of bovine mastitis. Application of this predictive model could aid early identification and prevention of mastitis in dairy cows, though the model requires further optimisation using a larger dataset.
Mapping the Human Visual Thalamus and its Cytoarchitectonic Subdivisions Using Quantitative MRI

The human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. A non-invasive assessment of the LGN and its functionally and microstructurally distinct magnocellular (M) and parvocellular (P) subdivisions in-vivo in humans is challenging, because of its small size and location deep inside the brain. Here we tested whether recent advances in high-field structural quantitative MRI (qMRI) can enable MR-based mapping of human LGN subdivisions. We employed ultra-high resolution 7 Tesla qMRI of a post-mortem human LGN specimen and high-resolution 7 Tesla in-vivo qMRI in a large participant sample. We found that a quantitative assessment of the LGN and a differentiation of its subdivisions was possible based on microstructure-informed MR-contrast alone. In both the post-mortem and in-vivo qMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through a subsequent ground truth histological examination of the same post-mortem LGN specimen, we showed that the observed T1 contrast pertains to cyto- and myeloarchitectonic differences between LGN subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy overcomes shortcomings of previous fMRI-based mapping approaches. It paves the way for an in-depth understanding of the function and microstructure of the LGN in humans. It also enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease. Significance Statement The lateral geniculate nucleus (LGN) is a key processing site for the analysis of visual information. Due to its small size and deep location within the brain, non-invasive mapping of the LGN and its microstructurally distinct subdivisions in humans is challenging. Using quantitative MRI methods that are sensitive to underlying microstructural tissue features, we show that a differentiation of the LGN and its microstructurally distinct subdivisions is feasible in humans non-invasively. These findings are important because they open up novel opportunities to assess the hitherto poorly understood complex role of the LGN in human perception and cognition, as well as the contribution of selective LGN subdivision impairments to various clinical conditions including developmental dyslexia, glaucoma and multiple sclerosis.
Super-resolution imaging uncovers the nanoscopic segregation of polarity proteins in epithelia

Epithelial tissues acquire their integrity and function through the apico-basal polarization of their constituent cells. Proteins of the PAR and Crumbs complexes are pivotal to epithelial polarization, but the mechanistic understanding of polarization is challenging to reach, largely because numerous potential interactions between these proteins and others have been found, without clear hierarchy in importance. We identify the regionalized and segregated organization of members of the PAR and Crumbs complexes at epithelial apical junctions by imaging endogenous proteins using STED microscopy on Caco-2 cells, human and murine intestinal samples. Proteins organize in submicrometric clusters, with PAR3 overlapping with the tight junction (TJ) while PALS1-PATJ and aPKC-PAR6β form segregated clusters that are apical of the TJ and present in an alternated pattern related to actin organization. CRB3A is also apical of the TJ and weakly overlaps with other polarity proteins. This organization at the nanoscale level significantly simplifies our view on how polarity proteins could cooperate to drive and maintain cell polarity.
Data Integration with SUMO Detects Latent Relationships Between Patients in Lower-Grade Gliomas

Joint analysis of multiple genomic data types can facilitate the discovery of complex mechanisms of biological processes and genetic diseases. We present a novel data integration framework based on non-negative matrix factorization that uses patient similarity networks. Our implementation supports continuous multi-omic datasets for molecular subtyping and handles missing data without using imputation, making it more efficient for genome-wide assays in large cohorts. Applying our approach to gene expression, microRNA expression, and methylation data from patients with lower grade gliomas, we identify a subtype with a significantly poorer prognosis. Tumors assigned to this subtype are hypomethylated genome-wide with a gain of AP-1 occupancy in the demethylated distal enhancers. These tumors’ genomic profiles are similar to Grade IV gliomas: they are enriched for somatic chr7 gain, chr10 loss, and other molecular events that have yet to be used in the diagnosis of lower-grade gliomas as per the current WHO guidelines.
Diverse Roles of MAX1 Homologues in Rice

Cytochrome P450 enzymes encoded by MORE AXILLARY GROWTH1 (MAX1)-like genes produce most of the structural diversity of strigolactones during the final steps of strigolactone biosynthesis. The diverse copies of MAX1 in Oryza sativa provide a resource to investigate why plants produce such a wide range of strigolactones. Here we performed in silico analyses of transcription factors and microRNAs that may regulate each rice MAX1, and compared the results with available data about MAX1 expression profiles and genes co-expressed with MAX1 genes. Data suggest that distinct mechanisms regulate the expression of each MAX1. Moreover, there may be novel functions for MAX1 homologues, such as the regulation of flower development or responses to heavy metals. In addition, individual MAX1s could be involved in specific functions, such as the regulation of seed development or wax synthesis in rice. Our analysis reveals potential new avenues of strigolactone research that may otherwise not be obvious.
New Genotypes and Diversity of Orientia tsutsugamushi Isolated from Scrub Typhus Patients in South Korea as Determined by Multilocus Sequence Typing

Orientia tsutsugamushi, an obligate intracellular organism, is the causative agent of scrub typhus, which is endemic in the Asia-Pacific region. No comparative studies on the genotypic properties of O. tsutsugamushi have been performed using multilocus sequence typing (MLST) in South Korea. Here, we characterized 51 clinical isolates from Jeonju, in southwestern Korea, and we compared them to isolates from Thailand, Laos, and Japan. We also identified 10 new alleles and six novel sequence types. Overall, our results suggest that the relative genetic stability and the clonal populations of O. tsutsugamushi strains in South Korea have remained mostly conserved. Author summary Scrub typhus is a life-threatening disease, caused by infection with O. tsutsugamushi, a Gram-negative intracellular bacterium. Approximately one million people are infected globally every year, especially in the Asia-Pacific region. Strains of O. tsutsugamushi are typically distinguished serologically on the basis of sequences of the highly polymorphic 56-kDa outer membrane protein. Multilocus sequence typing (MLST) is a generic typing method that provides a unified bacterial isolate characterization approach that can be used for evolutionary and population studies of bacteria. In this study, we describe the development and application of a MLST scheme that was applied to 51 O. tsutsugamushi isolates. We found 10 new alleles and six new STs, which yielded a total of seven O. tsutsugamushi STs in South Korea. Among seven different STs (ST 48, 93-98), ST 48 account for the largest proportion (49.0%) of O. tsutsugamushi STs in South Korea. With the exception of the appearance of six novel STs, the clonal populations have remained conserved but further study of population structure and evolutionary trends is warranted.
Short Communication: Antioxidant capacity in the intestinal mucosa of weanling piglets fed diets containing Fusarium mycotoxins and the efficacy of commercial supplements sold as detoxifiers

Le Thanh, B. V. , Lessard, M. , Chorfi, Y. and Guay, F. 2015. Short Communication: Antioxidant capacity in the intestinal mucosa of weanling piglets fed diets containing Fusarium mycotoxins and the efficacy of commercial supplements sold as detoxifiers. Can. J. Anim. Sci. 95: 569-575. The ability of commercial feed additives to prevent oxidative damage due to deoxynivalenol (DON) in piglets was studied. Sixty piglets (6.0±0.5 kg) were assigned randomly to six wheat-corn-soybean diets: control (<0.5 mg kg-1 DON), DON-rich diet (4 mg kg-1 DON), and four DON-rich diets supplemented with either glucomannan (DON+GLUC), yeast, live bacteria, enzymes and plant extract (DON+YBP), aluminosilicate (DON+ALS), or a mixture of preservatives (DON+PV). Malondialdehyde concentration (MDA), glutathione peroxidase activity (GPx), catalase activity (CAT) and superoxide dismutase activity (SOD) in the small intestine were measured after 14 d. The DON-rich diet increased MDA in the jejunum while decreasing CAT in the jejunum and SOD in the ileum and increasing GPx in the ileum (P<0.05). The DON+GLUC diet decreased GPx and SOD (P<0.05) and tended to decrease MDA in the jejunum (P<0.10). The DON+YBP, DON+PV and DON+ALS diets all decreased CAT in the jejunum, while DON+YBP and DON+PV also did so in the ileum (P<0.05). DON+GLUC decreased SOD in the jejunum, while DON+YBP increased it (P<0.05). In the ileum, DON+PV decreased SOD, while DON+ALS increased GPx (P<0.05). No significant differences in total antioxidant capacity (TAC) in intestinal tissues were found. This study demonstrates that the mycotoxin DON and anti-mycotoxin additives modify oxidative status, including the antioxidant enzyme activities (CAT, SOD or GPx) in the intestinal mucosa of piglets. However, it was not possible to identify a specific antioxidant enzyme involved in counteracting the effect of DON.