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Klebsiella pneumoniae is a pathogen associated with various infection types, which often exhibits multiple antibiotic resistance. Phages, or bacterial viruses, have an ability to specifically target and destroy K. pneumoniae, offering a potential means of combatting multidrug-resistant infections. Phage enzymes are another promising therapeutic agent that can break down bacterial capsular polysaccharide, which shields K. pneumoniae from the immune response and external factors. In this study, Klebsiella phage K5 was isolated; this phage is active against Klebsiella pneumoniae with the capsular type K21. It was demonstrated that the phage can effectively lyse the host culture. The adsorption apparatus of the phage has revealed two receptor-binding proteins (RBPs) with predicted polysaccharide depolymerising activity. A recombinant form of both RBPs was obtained and experiments showed that one of them depolymerised the capsular polysaccharide K21. The structure of this polysaccharide and its degradation fragments were analysed. The second receptor-binding protein showed no activity on capsular polysaccharide of any of the 31 capsule types tested, so the substrate for this enzyme remains to be determined in the future. Klebsiella phage K5 may be considered a useful agent against Klebsiella infections.
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Bacteriófagos , Infecções por Klebsiella , Humanos , Klebsiella , Klebsiella pneumoniae/metabolismo , Bacteriófagos/fisiologia , Infecções por Klebsiella/microbiologia , Polissacarídeos Bacterianos/metabolismoRESUMO
ABSTRACT: Guilherme, JPLF, Semenova, EA, Borisov, OV, Kostryukova, ES, Vepkhvadze, TF, Lysenko, EA, Andryushchenko, ON, Andryushchenko, LB, Lednev, EM, Larin, AK, Bondareva, EA, Generozov, EV, and Ahmetov, II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res 36(7): 1884-1889, 2022-The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. A recent study suggested that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition, and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 men, 51 women). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes, and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 [7.8] vs. 50.3 [15.8]%, p = 0.0015; all subjects: 64.1 ± 7.9 vs. 49.6 ± 14.7%, p = 0.0002). Furthermore, the A-allele was associated (p = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared with controls (7.7 vs. 2.4%, p = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared with controls (odds ratio [OR]: 3.43, p = 0.00071) or endurance athletes (OR: 2.36, p = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.
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Fator Neurotrófico Derivado do Encéfalo , Força da Mão , Fibras Musculares de Contração Rápida , Alelos , Atletas , Fator Neurotrófico Derivado do Encéfalo/genética , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Força Muscular/fisiologiaRESUMO
Microbiome spectra serve as critical clues to elucidate the evolutionary biology pathways, potential pathologies, and even behavioral patterns of the host organisms. Furthermore, exotic sources of microbiota represent an unexplored niche to discover microbial secondary metabolites. However, establishing the bacterial functionality is complicated by an intricate web of interactions inside the microbiome. Here we apply an ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling of the entire oral microbial community of the Siberian bear to isolate Bacillus strains demonstrating antimicrobial activity against Staphylococcus aureus Genome mining allowed us to identify antibiotic amicoumacin A (Ami) as responsible for inhibiting the growth of S. aureus Proteomics and metabolomics revealed a unique mechanism of Bacillus self-resistance to Ami, based on a subtle equilibrium of its deactivation and activation by kinase AmiN and phosphatase AmiO, respectively. We developed uHT quantitative single-cell analysis to estimate antibiotic efficacy toward different microbiomes and used it to determine the activity spectra of Ami toward human and Siberian bear microbiota. Thus, uHT microfluidic droplet platform activity profiling is a powerful tool for discovering antibiotics and quantifying external influences on a microbiome.
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Antibacterianos/farmacologia , Cumarínicos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Metabolômica/métodos , Animais , Antibacterianos/metabolismo , Bacillus pumilus/efeitos dos fármacos , Bacillus pumilus/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cumarínicos/metabolismo , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Farmacorresistência Bacteriana/fisiologia , Microbioma Gastrointestinal/fisiologia , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Dispositivos Lab-On-A-Chip , Proteômica/métodos , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Análise de Célula Única/métodos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Ursidae/microbiologiaRESUMO
The purpose of this study was to explore the association of the MCT1 gene Glu490Asp polymorphism (rs1049434) with athletic status and performance of endurance athletes. A total of 1,208 Brazilians (318 endurance athletes and 890 non-athletes) and 867 Europeans (315 endurance athletes and 552 non-athletes) were evaluated in a case-control approach. Brazilian participants were classified based on self-declared ethnicity to test whether the polymorphism was different between Caucasians and Afro-descendants. Moreover, 66 Hungarian athletes underwent an incremental test until exhaustion to assess blood lactate levels, while 46 Russian athletes had their maximum oxygen uptake ( V â O 2 max ) compared between genotypes. In the Brazilian cohort, the major T-allele was more frequent in Caucasian top-level competitors compared to their counterparts of lower competitive level (P = 0.039), and in Afro-descendant athletes compared to non-athletes (P = 0.015). Similarly, the T-allele was more frequent in European athletes (P = 0.029). Meta-analysis of the Brazilian and European cohorts confirmed that the T-allele is over-represented in endurance athletes (OR: 1.48, P = 0.03), especially when Afro-descendant athletes were included in the meta-analysis (OR: 1.58, P = 0.005). Furthermore, carriers of the T/T genotype accumulated less blood lactate in response to intense effort (P < 0.01) and exhibited higher V â O 2 max (P = 0.04). In conclusion, the Glu490Asp polymorphism was associated with endurance athletic status and performance. Our findings suggest that, although ethnic differences may exist, the presence of the major T-allele (i.e., the Glu-490 allele) favours endurance performance more than the mutant A-allele (i.e., the 490-Asp allele).
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An amendment to this paper has been published and can be accessed via the original article.
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BACKGROUND: Salivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today. RESULTS: We annotated the Hirudo medicinalis genome and performed RNA-seq on salivary cells isolated from three closely related leech species, H. medicinalis, Hirudo orientalis, and Hirudo verbana. Differential expression analysis verified by proteomics identified salivary cell-specific gene expression, many of which encode previously unknown salivary components. However, the genes encoding known anticoagulants have been found to be expressed not only in salivary cells. The function-related analysis of the unique salivary cell genes enabled an update of the concept of interactions between salivary proteins and components of haemostasis. CONCLUSIONS: Here we report a genome draft of Hirudo medicinalis and describe identification of novel salivary proteins and new homologs of genes encoding known anticoagulants in transcriptomes of three medicinal leech species. Our data provide new insights in genetics of blood-feeding lifestyle in leeches.
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Genoma , Hirudo medicinalis/genética , Proteínas e Peptídeos Salivares/genética , Animais , Anticoagulantes/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hirudo medicinalis/metabolismo , Sanguessugas/classificação , Sanguessugas/genética , Sanguessugas/metabolismo , Proteômica , Saliva/metabolismo , Proteínas e Peptídeos Salivares/metabolismoRESUMO
MOTIVATION: The resistance of bacterial pathogens to antibiotics is one of the most important issues of modern health care. The human microbiota can accumulate resistance determinants and transfer them to pathogenic microbiota by means of horizontal gene transfer. Thus, it is important to develop methods of prediction and monitoring of antibiotics resistance in human populations. RESULTS: We present the agent-based VERA model, which allows simulation of the spread of pathogens, including the possible horizontal transfer of resistance determinants from a commensal microbiota community. The model considers the opportunity of residents to stay in the town or in a medical institution, have incorrect self-treatment, treatment with several antibiotics types and transfer and accumulation of resistance determinants from commensal microorganism to a pathogen. In this model, we have also created an assessment of optimum observation frequency of infection spread among the population. Investigating model behavior, we show a number of non-linear dependencies, including the exponential nature of the dependence of the total number of those infected on the average resistance of a pathogen. As the model infection, we chose infection with Shigella spp., though it could be applied to a wide range of other pathogens. AVAILABILITY AND IMPLEMENTATION: Source code and binaries VERA and VERA.viewer are freely available for download at github.com/lpenguin/microbiota-resistome. The code is written in Java, JavaScript and R for Linux platform. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Microbioma Gastrointestinal , Antibacterianos , Resistência Microbiana a Medicamentos , Transferência Genética Horizontal , Humanos , Análise de SistemasRESUMO
PURPOSE: Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in the HFE is associated with elevated iron indexes and may give some advantage in endurance-oriented sports. The aim of the present study was to investigate the association between the HFE H63D polymorphism and elite endurance athlete status in Japanese and Russian populations, aerobic capacity and to perform a meta-analysis using current findings and three previous studies. METHODS: The study involved 315 international-level endurance athletes (255 Russian and 60 Japanese) and 809 healthy controls (405 Russian and 404 Japanese). Genotyping was performed using micro-array analysis or by PCR. VO2max in 46 male Russian endurance athletes was determined using gas analysis system. RESULTS: The frequency of the iron-increasing CG/GG genotypes was significantly higher in Russian (38.0 vs 24.9%; OR 1.85, P = 0.0003) and Japanese (13.3 vs 5.0%; OR 2.95, P = 0.011) endurance athletes compared to ethnically matched controls. The meta-analysis using five cohorts (two French, Japanese, Spanish, and Russian; 586 athletes and 1416 controls) showed significant prevalence of the CG/GG genotypes in endurance athletes compared to controls (OR 1.96, 95% CI 1.58-2.45; P = 1.7 × 10-9). Furthermore, the HFE G allele was associated with high VÌO2max in male athletes [CC: 61.8 (6.1), CG/GG: 66.3 (7.8) ml/min/kg; P = 0.036]. CONCLUSIONS: We have shown that the HFE H63D polymorphism is strongly associated with elite endurance athlete status, regardless ethnicities and aerobic capacity in Russian athletes.
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Proteína da Hemocromatose/genética , Resistência Física/genética , Atletas , Estudos de Casos e Controles , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Ultrahigh-throughput screening (uHTS) techniques can identify unique functionality from millions of variants. To mimic the natural selection mechanisms that occur by compartmentalization in vivo, we developed a technique based on single-cell encapsulation in droplets of a monodisperse microfluidic double water-in-oil-in-water emulsion (MDE). Biocompatible MDE enables in-droplet cultivation of different living species. The combination of droplet-generating machinery with FACS followed by next-generation sequencing and liquid chromatography-mass spectrometry analysis of the secretomes of encapsulated organisms yielded detailed genotype/phenotype descriptions. This platform was probed with uHTS for biocatalysts anchored to yeast with enrichment close to the theoretically calculated limit and cell-to-cell interactions. MDE-FACS allowed the identification of human butyrylcholinesterase mutants that undergo self-reactivation after inhibition by the organophosphorus agent paraoxon. The versatility of the platform allowed the identification of bacteria, including slow-growing oral microbiota species that suppress the growth of a common pathogen, Staphylococcus aureus, and predicted which genera were associated with inhibitory activity.
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Butirilcolinesterase/química , Ensaios de Triagem em Larga Escala/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Paraoxon/química , Análise de Célula Única/instrumentação , Antibiose , Biodiversidade , Comunicação Celular , Emulsões , Citometria de Fluxo , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Óleos Voláteis/química , Fenótipo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Água/químicaRESUMO
Díaz, J, Álvarez Herms, J, Castañeda, A, Larruskain, J, Ramírez de la Piscina, X, Borisov, OV, Semenova, EA, Kostryukova, ES, Kulemin, NA, Andryushchenko, ON, Larin, AK, Andryushchenko, LB, Generozov, EV, Ahmetov, II, and Odriozola, A. The GALNTL6 gene rs558129 polymorphism is associated with power performance. J Strength Cond Res 34(11): 3031-3036, 2020-The largest genome-wide association study to date in sports genomics showed that endurance athletes were 1.23 times more likely to possess the C allele of the single nucleotide polymorphism rs558129 of N-acetylgalactosaminyltransferase-like 6 gene (GALNTL6), compared with controls. Nevertheless, no further study has investigated GALNTL6 gene in relation to physical performance. Considering that previous research has shown that the same polymorphism can be associated with both endurance and power phenotypes (ACTN3, ACE, and PPARA), we investigated the association between GALNTL6 rs558129 polymorphism and power performance. According to this objective we conducted 2 global studies regarding 2 different communities of athletes in Spain and Russia. The first study involved 85 Caucasian physically active men from the north of Spain to perform a Wingate anaerobic test (WAnT). In the second study we compared allelic frequencies between 173 Russian power athletes (49 strength and 124 speed-strength athletes), 169 endurance athletes, and 201 controls. We found that physically active men with the T allele of GALNTL6 rs558129 had 5.03-6.97% higher power values compared with those with the CC genotype (p < 0.05). Consistent with these findings, we have shown that the T allele was over-represented in power athletes (37.0%) compared with endurance athletes (29.3%; OR = 1.4, p = 0.032) and controls (28.6%; OR = 1.5, p = 0.015). Furthermore, the highest frequency of the T allele was observed in strength athletes (43.9%; odds ratio [OR] = 1.9, p = 0.0067 compared with endurance athletes; OR = 2.0, p = 0.0036 compared with controls). In conclusion, our data suggest that the GALNTL6 rs558129 T allele can be favorable for anaerobic performance and strength athletes. In addition, we propose a new possible functional role of GALNTL6 rs558129, gut microbiome regarding short-chain fatty acid regulation and their anti-inflammatory and resynthesis functions. Nevertheless, further studies are required to understand the mechanisms involved.
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Atletas , Desempenho Atlético/fisiologia , Força Muscular/genética , Resistência Física/genética , Esportes/fisiologia , Adulto , Alelos , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , N-Acetilgalactosaminiltransferases/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Federação Russa , Espanha , População Branca/genética , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
Whole genome sequencing (WGS) has great potential to explore all possible DNA variants associated with physical performance, psychological traits and health conditions of athletes. Here we present, for the first time, annotation of genomic variants of elite athletes, based on the WGS of 20 Tatar male wrestlers. The maximum number of high-quality variants per sample was over 3.8 M for single nucleotide polymorphisms (SNPs) and about 0.64 M for indels. The maximum number of nonsense mutations was 148 single nucleotide variants (SNVs) per individual. Athletes' genomes on average contained 18.9 nonsense SNPs in a homozygous state per sample, while non-athletes' exomes (Tatar controls, n = 19) contained 18 nonsense SNPs. Finally, we applied genomic data for the association analysis and used reaction time (RT) as an example. Out of 1884 known genome-wide significant SNPs related to RT, we identified four SNPs (KIF27 rs10125715, APC rs518013, TMEM229A rs7783359, LRRN3 rs80054135) associated with RT in wrestlers. The cumulative number of favourable alleles (KIF27 A, APC A, TMEM229A T, LRRN3 T) was significantly correlated with RT both in wrestlers (P = 0.0003) and an independent cohort (n = 43) of physically active subjects (P = 0.029). Furthermore, we found that the frequencies of the APC A (53.3 vs 44.0%, P = 0.033) and LRRN3 T (7.5 vs 2.8%, P = 0.009) alleles were significantly higher in elite athletes (n = 107) involved in sports with RT as an essential component of performance (combat sports, table tennis and volleyball) compared to less successful (n = 176) athletes. The LRRN3 T allele was also over-represented in elite athletes (7.5%) in comparison with 189 controls (2.9%, P = 0.009). In conclusion, we present the first WGS study of athletes showing that WGS can be applied in sport and exercise science.
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Motivation: Antibiotic resistance is an important global public health problem. Human gut microbiota is an accumulator of resistance genes potentially providing them to pathogens. It is important to develop tools for identifying the mechanisms of how resistance is transmitted between gut microbial species and pathogens. Results: We developed MetaCherchant-an algorithm for extracting the genomic environment of antibiotic resistance genes from metagenomic data in the form of a graph. The algorithm was validated on a number of simulated and published datasets, as well as applied to new 'shotgun' metagenomes of gut microbiota from patients with Helicobacter pylori who underwent antibiotic therapy. Genomic context was reconstructed for several major resistance genes. Taxonomic annotation of the context suggests that within a single metagenome, the resistance genes can be contained in genomes of multiple species. MetaCherchant allows reconstruction of mobile elements with resistance genes within the genomes of bacteria using metagenomic data. Application of MetaCherchant in differential mode produced specific graph structures suggesting the evidence of possible resistance gene transmission within a mobile element that occurred as a result of the antibiotic therapy. MetaCherchant is a promising tool giving researchers an opportunity to get an insight into dynamics of resistance transmission in vivo basing on metagenomic data. Availability and implementation: Source code and binaries are freely available for download at https://github.com/ctlab/metacherchant. The code is written in Java and is platform-independent. Cotanct: ulyantsev@rain.ifmo.ru. Supplementary information: Supplementary data are available at Bioinformatics online.
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Bactérias/genética , Farmacorresistência Bacteriana/genética , Microbioma Gastrointestinal/genética , Metagenômica/métodos , Software , Algoritmos , HumanosRESUMO
BACKGROUND: Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes. RESULTS: We have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost â¼1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome. CONCLUSIONS: The FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.
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Transplante de Microbiota Fecal , Fezes/microbiologia , Microbioma Gastrointestinal , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Fatores de TempoRESUMO
Yield of protein per translated mRNA may vary by four orders of magnitude. Many studies analyzed the influence of mRNA features on the translation yield. However, a detailed understanding of how mRNA sequence determines its propensity to be translated is still missing. Here, we constructed a set of reporter plasmid libraries encoding CER fluorescent protein preceded by randomized 5Î untranslated regions (5Î-UTR) and Red fluorescent protein (RFP) used as an internal control. Each library was transformed into Escherchia coli cells, separated by efficiency of CER mRNA translation by a cell sorter and subjected to next generation sequencing. We tested efficiency of translation of the CER gene preceded by each of 48 natural 5Î-UTR sequences and introduced random and designed mutations into natural and artificially selected 5Î-UTRs. Several distinct properties could be ascribed to a group of 5Î-UTRs most efficient in translation. In addition to known ones, several previously unrecognized features that contribute to the translation enhancement were found, such as low proportion of cytidine residues, multiple SD sequences and AG repeats. The latter could be identified as translation enhancer, albeit less efficient than SD sequence in several natural 5Î-UTRs.
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Regiões 5' não Traduzidas , Escherichia coli/genética , Biossíntese de Proteínas , Sequências Reguladoras de Ácido Ribonucleico , Separação Celular , Citometria de Fluxo , Genes Reporter , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Conformação de Ácido Nucleico , Nucleotídeos/fisiologiaRESUMO
Guilherme, JPLF, Egorova, ES, Semenova, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Ospanova, EA, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Govorun, VM, Generozov, EV, Ahmetov, II, and Lancha Junior, AH. The A-allele of the FTO gene rs9939609 polymorphism is associated with decreased proportion of slow oxidative muscle fibers and over-represented in heavier athletes. J Strength Cond Res 33(3): 691-700, 2019-The purpose of this study was to explore the frequency of the FTO T > A (rs9939609) polymorphism in elite athletes from 2 cohorts (Brazil and Russia), as well as to find a relationship between FTO genotypes and muscle fiber composition. A total of 677 athletes and 652 nonathletes were evaluated in the Brazilian cohort, whereas a total of 920 athletes and 754 nonathletes were evaluated in the Russian cohort. It was found a trend for a lower frequency of A/A genotype in long-distance athletes compared with nonathletes (odds ratio [OR]: 0.65; p = 0.054). By contrast, it was found an increased frequency of the A-allele in Russian power athletes. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a Russian power athlete compared with matched nonathletes (OR: 1.45; p = 0.002). Different from that observed in combat sports athletes of lighter weight categories, the A-allele was also over-represented in combat sports athletes of heavier weight categories. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a combat sports athlete of heavier weight categories compared with nonathletes (OR: 1.79; p = 0.018). Regarding the muscle fibers, we found that carriers of the A/A genotype had less slow-twitch muscle fibers than T-allele carriers (p = 0.029). In conclusion, the A/A genotype of the FTO T > A polymorphism is under-represented in athletes more reliant on a lean phenotype and associated with decreased proportion of slow-twitch muscle fibers, while is over-represented in strength and heavier athletes.
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Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Atletas , Peso Corporal/fisiologia , Fibras Musculares de Contração Lenta/metabolismo , Força Muscular/fisiologia , Esportes/fisiologia , Adulto , Alelos , Brasil , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Estresse Oxidativo , Fenótipo , Polimorfismo de Nucleotídeo Único , Federação Russa , Adulto JovemRESUMO
Grishina, EE, Zmijewski, P, Semenova, EA, Cieszczyk, P, Huminska-Lisowska, K, Michalowska-Sawczyn, M, Maculewicz, E, Crewther, B, Orysiak, J, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Bondareva, EA, Erskine, RM, Generozov, EV, and Ahmetov, II. Three DNA polymorphisms previously identified as markers for handgrip strength are associated with strength in weightlifters and muscle fiber hypertrophy. J Strength Cond Res 33(10): 2602-2607, 2019-Muscle strength is a highly heritable trait. So far, 196 single nucleotide polymorphisms (SNPs) associated with handgrip strength have been identified in 3 genome-wide association studies. The aim of our study was to validate the association of 35 SNPs with strength of elite Russian weightlifters and replicate the study in Polish weightlifters. Genotyping was performed using micro-array analysis or real-time polymerase chain reaction. We found that the rs12055409 G-allele near the MLN gene (p = 0.004), the rs4626333 G-allele near the ZNF608 gene (p = 0.0338), and the rs2273555 A-allele in the GBF1 gene (p = 0.0099) were associated with greater competition results (total lifts in snatch and clean and jerk adjusted for sex and weight) in 53 elite Russian weightlifters. In the replication study of 76 sub-elite Polish weightlifters, rs4626333 GG homozygotes demonstrated greater competition results (p = 0.0155) and relative muscle mass (p = 0.046), adjusted for sex, weight, and age, compared with carriers of the A-allele. In the following studies, we tested the hypotheses that these SNPs would be associated with skeletal muscle hypertrophy and handgrip strength. We found that the number of strength-associated alleles was positively associated with fast-twitch muscle fiber cross-sectional area in the independent cohort of 20 male power athletes (p = 0.021) and with handgrip strength in 87 physically active individuals (p = 0.015). In conclusion, by replicating previous findings in 4 independent studies, we demonstrate that the rs12055409 G-, rs4626333 G-, and rs2273555 A-alleles are associated with higher levels of strength, muscle mass, and muscle fiber size.
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Desempenho Atlético/fisiologia , Força da Mão/fisiologia , Fibras Musculares de Contração Rápida/citologia , Força Muscular/genética , Levantamento de Peso/fisiologia , Adolescente , Adulto , Alelos , DNA/análise , Feminino , Estudo de Associação Genômica Ampla , Fatores de Troca do Nucleotídeo Guanina/genética , Homozigoto , Humanos , Hipertrofia/genética , Masculino , Proteínas Musculares/genética , Força Muscular/fisiologia , Polônia , Polimorfismo de Nucleotídeo Único , Federação Russa , Fatores de Transcrição/genética , Adulto JovemRESUMO
Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leonska-Duniec, A, Pajak, B, Chycki, J, Moska, W, Lulinska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cieszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.
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Desempenho Atlético/fisiologia , Corrida/fisiologia , Futebol/fisiologia , População Branca/genética , 17-Hidroxiesteroide Desidrogenases/genética , Aceleração , Adolescente , Alelos , Angiotensinogênio/genética , Criança , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fator de Crescimento Insulin-Like II/genética , Interleucina-6/genética , Masculino , Polônia , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Receptores Adrenérgicos beta 2/genética , Federação Russa , Reino Unido , Adulto JovemRESUMO
BACKGROUND: Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated. METHODS: We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability. RESULTS: The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes. CONCLUSIONS: The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease.
Assuntos
Doença de Crohn/patologia , Escherichia coli/genética , Microbioma Gastrointestinal , Variação Genética , Metagenômica/métodos , Análise por Conglomerados , Doença de Crohn/microbiologia , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Genoma Bacteriano , Humanos , Mucosa Intestinal/microbiologiaRESUMO
Located on the shore of Kandalaksha Bay (the White Sea, Russia) and previously separated from it, Trekhtzvetnoe Lake (average depth 3.5 m) is one of the shallowest meromictic lakes known. Despite its shallowness, it features completely developed water column stratification with high-density microbial chemocline community (bacterial plate) and high rates of major biogeochemical processes. A sharp halocline stabilizes the stratification. Chlorobium phaeovibrioides dominated the bacterial plate, which reached a density of 2 × 108 cell ml-1 and almost completely intercepts H2 S diffusion from the anoxic monimolimnion. The resulting anoxygenic photosynthesis rate reached 240 µmol C l-1 day-1 , exceeding the oxygenic photosynthesis rate in the mixolimnion. The rates of other processes are also high, reaching 4.5 µmol CH4 l-1 day-1 for methane oxidation and 35 µmol S l-1 day-1 for sulfate reduction. Metagenomic analysis demonstrated that the Chl. phaeovibrioides population in the bacterial plate layer had nearly clonal homogeneity, although some fraction of these cells harbour a plasmid. The Chlorobium population was associated with bacteriophages that share homology with CRISPR spacers in the host. These features make the ecosystem of the Trekhtzvetnoe Lake a valuable model for studying regulation and evolution processes in natural high-density microbial systems.
Assuntos
Bactérias/isolamento & purificação , Lagos/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Ecossistema , Lagos/química , Metano/análise , Metano/metabolismo , Oxirredução , Oxigênio/análise , Oxigênio/metabolismo , Fotossíntese , Federação RussaRESUMO
We aimed to replicate, in a specific athletic event cohort (only track and field) and in two different ethnicities (Japanese and East European, i.e. Russian and Polish), original findings showing the association of the angiotensin-II receptor type-2 gene (AGTR2) rs11091046 A>C polymorphism with athlete status. We compared genotypic frequencies of the AGTR2 rs11091046 polymorphism among 282 track and field sprint/power athletes (200 men and 82 women), including several national record holders and Olympic medallists (214 Japanese, 68 Russian and Polish), and 2024 control subjects (842 men and 1182 women) (804 Japanese, 1220 Russian and Polish). In men, a meta-analysis from the two combined cohorts showed a significantly higher frequency of the C allele in athletes than in controls (odds ratio: 1.62, P=0.008, heterogeneity index I 2 =0%). With regard to respective cohorts, C allele frequency was higher in Japanese male athletes than in controls (67.7% vs. 55.9%, P=0.022), but not in Russian/Polish male athletes (61.9% vs. 51.0%, P=0.172). In women, no significant results were obtained by meta-analysis for the two cohorts combination (P=0.850). The AC genotype frequency was significantly higher in Russian/Polish women athletes than in controls (69.2% vs. 42.1%, P=0.022), but not in Japanese women athletes (P=0.226). Our results, in contrast to previous findings, suggested by meta-analysis that the C allele of the AGTR2 rs11091046 polymorphism is associated with sprint/power track and field athlete status in men, but not in women.