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Femoral head separation (FHS) is characterized by the detachment of growth plate (GP) and articular cartilage, occurring in tibia and femur. However, the molecular mechanisms involved with this condition are not completely understood. Therefore, genes and biological processes (BP) involved with FHS were identified in 21-day-old broilers through RNA sequencing of the femoral GP. 13,487 genes were expressed in the chicken femoral head transcriptome of normal and FHS-affected broilers. From those, 34 were differentially expressed (DE; FDR ≤0.05) between groups, where all of them were downregulated in FHS-affected broilers. The main BP were enriched in receptor signaling pathways, ossification, bone mineralization and formation, skeletal morphogenesis, and vascularization. RNA-Seq datasets comparison of normal and FHS-affected broilers with 21, 35 and 42 days of age has shown three shared DE genes (FBN2, C1QTNF8, and XYLT1) in GP among ages. Twelve genes were exclusively DE at 21 days, where 10 have already been characterized (SHISA3, FNDC1, ANGPTL7, LEPR, ENSGALG00000049529, OXTR, ENSGALG00000045154, COL16A1, RASD2, BOC, GDF10, and THSD7B). Twelve SNPs were associated with FHS (p < 0.0001). Out of those, 5 were novel and 7 were existing variants located in 7 genes (RARS, TFPI2, TTI1, MAP4K3, LINK54, and AREL1). We have shown that genes related to chondrogenesis and bone differentiation were downregulated in the GP of FHS-affected young broilers. Therefore, these findings evince that candidate genes pointed out in our study are probably related to the onset of FHS in broilers.

Made available in DSpace on 2022-04-29T08:46:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-28 Center for Information Technology Center for Scientific Review National Institutes of Health Office of Extramural Research, National Institutes of Health Office of Research Infrastructure Programs, National Institutes of Health Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as “discordant couples”. We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners. Department of Pathology School of Medicine São Paulo State University (UNESP) Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit School of Medicine São Paulo State University (UNESP) Human Genome and Stem Cell Research Center University of São Paulo Department of Genetics and Evolutionary Biology Biosciences Institute University of São Paulo Centro Universitário Sudoeste Paulista Departamento de Química Faculdade de Filosofa Ciências e Letras de Ribeirão Preto Universidade de São Paulo Department of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of São Paulo Departamento de Clínica Médica Disciplina de Alergia e Imunologia Clínica Faculdade de Medicina da Universidade de São Paulo Laboratório de Imunologia Instituto do Coração (InCor) LIM19 Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) Instituto de Investigação em Imunologia - Instituto Nacional de Ciências e Tecnologia-iii-INCT Department of Pathology School of Medicine São Paulo State University (UNESP) Molecular Genetics and Bioinformatics Laboratory–Experimental Research Unit School of Medicine São Paulo State University (UNESP) CAPES: 001 FAPESP: 2013/08028-1 FAPESP: 2013/17084-0 FAPESP: 2014/50931-3 FAPESP: 2017/19223-0 FAPESP: 2019/19998-8 FAPESP: 2020/09702-1 CNPq: 465355/2014-5

In the myrmecophytic mutualistic relationship between Azteca ants and Cecropia plants both species receive protection and exchange nutrients. The presence of microorganisms in this symbiotic system has been reported, and the symbiotic role of some fungi involved in the myrmecophytic interactions has been described. In this work we focus on bacteria within this mutualism, conducting isolations and screening for antimicrobial activities, genome sequencing, and biochemical characterization. We show that Pantoea, Rhizobium, Methylobacterium, Streptomyces and Pseudomonas are the most common cultivable genera of bacteria. Interestingly, Pseudomonas spp. isolates showed potent activity against 83% of the pathogens tested in our antimicrobial activity assays, including a phytopathogenic fungus isolated from Cecropia samples. Given the predicted nitrogen limitations associated with the fungal patches within this myrmecophyte, we performed nitrogen fixation analyses on the bacterial isolates within the Proteobacteria and show the potential for nitrogen fixation in Pseudomonas strains. The genome of one Pseudomonas strain was sequenced and analyzed. The gene cluster involved in the biosynthesis of cyclic lipodepsipeptides (CLPs) was identified, and we found mutations that may be related to the loss of function in the dual epimerization/condensation domains. The compound was isolated, and its structure was determined, corresponding to the antifungal viscosinamide. Our findings of diazotrophy and production of viscosinamide in multiple Pseudomonas isolates suggests that this bacterial genus may play an important role in the Cecropia-Azteca symbiosis.

Mycobacterium bovis is the main causative agent of zoonotic tuberculosis in humans and frequently devastates livestock and wildlife worldwide. Previous studies suggested the existence of genetic groups of M. bovis strains based on limited DNA markers (a.k.a. clonal complexes), and the evolution and ecology of this pathogen has been only marginally explored at the global level. We have screened over 2,600 publicly available M. bovis genomes and newly sequenced four wildlife M. bovis strains, gathering 1,969 genomes from 23 countries and at least 24 host species, including humans, to complete a phylogenomic analyses. We propose the existence of four distinct global lineages of M. bovis (Lb1, Lb2, Lb3, and Lb4) underlying the current disease distribution. These lineages are not fully represented by clonal complexes and are dispersed based on geographic location rather than host species. Our data divergence analysis agreed with previous studies reporting independent archeological data of ancient M. bovis (South Siberian infected skeletons at similar to 2,000 years before present) and indicates that extant M. bovis originated between 715 and 3,556 years BP, with later emergence in the New World and Oceania, likely influenced by trades among countries. CNPq (Conselho Nacional de Pesquisa Cientifica), Ministry of Science, Brazil [134266/2017-0, 140003/2019-3]; CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior), Ministry of Education, BrazilCAPES [88887.283881/2018-00, 1650900, 1539669]; Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2017/04617-3, 2017/20147-7]; CAPESCAPES [001]; Morris Animal Foundation [D17ZO-307] Fellowships for CZ, JP, ACG, TS-P, NC, AS, and CI are provided by CNPq (Conselho Nacional de Pesquisa Cientifica), Ministry of Science, Brazil (134266/2017-0 and 140003/2019-3), CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior), Ministry of Education, Brazil (88887.283881/2018-00; 1650900; and 1539669) and Sao Paulo Research Foundation (FAPESP) (2017/04617-3 and 2017/20147-7). This study was financed in part by CAPES (Finance Code 001). Main research funding was made available through Morris Animal Foundation (grant number D17ZO-307).

Chronic granulomatous disease (CGD) is an inherited, genetically heterogeneous disease characterized by defective phagocytic cell microbicidal function, leading to increased susceptibility to bacterial and fungal infections. CGD is caused by mutations in components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, which is responsible for reactive oxygen species production during phagocytosis. Mutations in the neutrophil cytosolic factor 2 (NCF2) gene account for