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1.
Int J Mol Sci ; 25(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38203780

RESUMO

The mainstream of the post-genome target-assisted breeding in crop plant species includes biofortification such as high-throughput phenotyping along with genome-based selection. Therefore, in this work, we used the Web-service Plant_SNP_TATA_Z-tester, which we have previously developed, to run a uniform in silico analysis of the transcriptional alterations of 54,013 protein-coding transcripts from 32,833 Arabidopsis thaliana L. genes caused by 871,707 SNPs located in the proximal promoter region. The analysis identified 54,993 SNPs as significantly decreasing or increasing gene expression through changes in TATA-binding protein affinity to the promoters. The existence of these SNPs in highly conserved proximal promoters may be explained as intraspecific diversity kept by the stabilizing natural selection. To support this, we hand-annotated papers on some of the Arabidopsis genes possessing these SNPs or on their orthologs in other plant species and demonstrated the effects of changes in these gene expressions on plant vital traits. We integrated in silico estimates of the TBP-promoter affinity in the AtSNP_TATAdb knowledge base and showed their significant correlations with independent in vivo experimental data. These correlations appeared to be robust to variations in statistical criteria, genomic environment of TATA box regions, plants species and growing conditions.


Assuntos
Arabidopsis , Arabidopsis/genética , Polimorfismo de Nucleotídeo Único , Melhoramento Vegetal , Biomarcadores , Regiões Promotoras Genéticas
2.
Int J Mol Sci ; 24(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37240120

RESUMO

The study of gene expression regulation raises the challenge of developing bioinformatics tools and algorithms, demanding data integration [...].


Assuntos
Algoritmos , Biologia Computacional , Regulação da Expressão Gênica
3.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36835409

RESUMO

Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone's any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.


Assuntos
Envelhecimento , Doença , Regulação da Expressão Gênica , Animais , Humanos , Ratos , Envelhecimento/genética , Perfilação da Expressão Gênica , Transcriptoma , Doença/genética
4.
Int J Mol Sci ; 24(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902311

RESUMO

It is well-established that double-stranded RNA (dsRNA) exhibits noticeable radioprotective and radiotherapeutic effects. The experiments conducted in this study directly demonstrated that dsRNA was delivered into the cell in its native form and that it induced hematopoietic progenitor proliferation. The 68 bp synthetic dsRNA labeled with 6-carboxyfluorescein (FAM) was internalized into mouse hematopoietic progenitors, c-Kit+ (a marker of long-term hematopoietic stem cells) cells and CD34+ (a marker of short-term hematopoietic stem cells and multipotent progenitors) cells. Treating bone marrow cells with dsRNA stimulated the growth of colonies, mainly cells of the granulocyte-macrophage lineage. A total of 0.8% of Krebs-2 cells internalized FAM-dsRNA and were simultaneously CD34+ cells. dsRNA in its native state was delivered into the cell, where it was present without any signs of processing. dsRNA binding to a cell was independent of cell charge. dsRNA internalization was related to the receptor-mediated process that requires energy from ATP. Synthetic dsRNA did not degrade in the bloodstream for at least 2 h. Hematopoietic precursors that had captured dsRNA reinfused into the bloodstream and populated the bone marrow and spleen. This study, for the first time, directly proved that synthetic dsRNA is internalized into a eukaryotic cell via a natural mechanism.


Assuntos
Células-Tronco Hematopoéticas , RNA de Cadeia Dupla , Animais , Camundongos , RNA de Cadeia Dupla/farmacologia , Células-Tronco Hematopoéticas/metabolismo , Medula Óssea/metabolismo , Antígenos CD34/metabolismo , Células da Medula Óssea/metabolismo , Células Cultivadas
5.
Int J Mol Sci ; 24(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38139225

RESUMO

Group-specific component macrophage-activating factor (GcMAF) is the vitamin D3-binding protein (DBP) deglycosylated at Thr420. The protein is believed to exhibit a wide range of therapeutic properties associated with the activation of macrophagal immunity. An original method for GcMAF production, DBP conversion to GcMAF, and the analysis of the activating potency of GcMAF was developed in this study. Data unveiling the molecular causes of macrophage activation were obtained. GcMAF was found to interact with three CLEC10A derivatives having molecular weights of 29 kDa, 63 kDa, and 65 kDa. GcMAF interacts with high-molecular-weight derivatives via Ca2+-dependent receptor engagement. Binding to the 65 kDa or 63 kDa derivative determines the pro- and anti-inflammatory direction of cytokine mRNA expression: 65 kDa-pro-inflammatory (TNF-α, IL-1ß) and 63 kDa-anti-inflammatory (TGF-ß, IL-10). No Ca2+ ions are required for the interaction with the canonical 29 kDa CLEC10A. Both forms, DBP protein and GcMAF, bind to the 29 kDa CLEC10A. This interaction is characterized by the stochastic mRNA synthesis of the analyzed cytokines. Ex vivo experiments have demonstrated that when there is an excess of GcMAF ligand, CLEC10A forms aggregate, and the mRNA synthesis of analyzed cytokines is inhibited. A schematic diagram of the presumable mechanism of interaction between the CLEC10A derivatives and GcMAF is provided. The principles and elements of standardizing the GcMAF preparation are elaborated.


Assuntos
Fatores Ativadores de Macrófagos , Macrófagos , Proteína de Ligação a Vitamina D , Anti-Inflamatórios , Fatores Ativadores de Macrófagos/metabolismo , Macrófagos/metabolismo , RNA Mensageiro , Humanos , Proteína de Ligação a Vitamina D/metabolismo
6.
Int J Mol Sci ; 23(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36499269

RESUMO

The body of scientific literature continues to grow annually. Over 1.5 million abstracts of biomedical publications were added to the PubMed database in 2021. Therefore, developing cognitive systems that provide a specialized search for information in scientific publications based on subject area ontology and modern artificial intelligence methods is urgently needed. We previously developed a web-based information retrieval system, ANDDigest, designed to search and analyze information in the PubMed database using a customized domain ontology. This paper presents an improved ANDDigest version that uses fine-tuned PubMedBERT classifiers to enhance the quality of short name recognition for molecular-genetics entities in PubMed abstracts on eight biological object types: cell components, diseases, side effects, genes, proteins, pathways, drugs, and metabolites. This approach increased average short name recognition accuracy by 13%.


Assuntos
Inteligência Artificial , Mineração de Dados , Mineração de Dados/métodos , PubMed , Bases de Dados Factuais , Proteínas
7.
Int J Mol Sci ; 23(5)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35269977

RESUMO

Although half of hypertensive patients have hypertensive parents, known hypertension-related human loci identified by genome-wide analysis explain only 3% of hypertension heredity. Therefore, mainstream transcriptome profiling of hypertensive subjects addresses differentially expressed genes (DEGs) specific to gender, age, and comorbidities in accordance with predictive preventive personalized participatory medicine treating patients according to their symptoms, individual lifestyle, and genetic background. Within this mainstream paradigm, here, we determined whether, among the known hypertension-related DEGs that we could find, there is any genome-wide hypertension theranostic molecular marker applicable to everyone, everywhere, anytime. Therefore, we sequenced the hippocampal transcriptome of tame and aggressive rats, corresponding to low and high stress reactivity, an increase of which raises hypertensive risk; we identified stress-reactivity-related rat DEGs and compared them with their known homologous hypertension-related animal DEGs. This yielded significant correlations between stress reactivity-related and hypertension-related fold changes (log2 values) of these DEG homologs. We found principal components, PC1 and PC2, corresponding to a half-difference and half-sum of these log2 values. Using the DEGs of hypertensive versus normotensive patients (as the control), we verified the correlations and principal components. This analysis highlighted downregulation of ß-protocadherins and hemoglobin as whole-genome hypertension theranostic molecular markers associated with a wide vascular inner diameter and low blood viscosity, respectively.


Assuntos
Hipertensão , Animais , Pressão Sanguínea/genética , Perfilação da Expressão Gênica , Humanos , Hipertensão/metabolismo , Ratos , Transcriptoma
8.
Int J Mol Sci ; 23(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36555446

RESUMO

An ability of poorly differentiated cells of different genesis, including tumor stem-like cells (TSCs), to internalize extracellular double-stranded DNA (dsDNA) fragments was revealed in our studies. Using the models of Krebs-2 murine ascites carcinoma and EBV-induced human B-cell lymphoma culture, we demonstrated that dsDNA internalization into the cell consists of several mechanistically distinct phases. The primary contact with cell membrane factors is determined by electrostatic interactions. Firm contacts with cell envelope proteins are then formed, followed by internalization into the cell of the complex formed between the factor and the dsDNA probe bound to it. The key binding sites were found to be the heparin-binding domains, which are constituents of various cell surface proteins of TSCs-either the C1q domain, the collagen-binding domain, or domains of positively charged amino acids. These results imply that the interaction between extracellular dsDNA fragments and the cell, as well as their internalization, took place with the involvement of glycocalyx components (proteoglycans/glycoproteins (PGs/GPs) and glycosylphosphatidylinositol-anchored proteins (GPI-APs)) and the system of scavenger receptors (SRs), which are characteristic of TSCs and form functional clusters of cell surface proteins in TSCs. The key provisions of the concept characterizing the principle of organization of the "group-specific" cell surface factors of TSCs of various geneses were formulated. These factors belong to three protein clusters: GPs/PGs, GIP-APs, and SRs. For TSCs of different tumors, these clusters were found to be represented by different members with homotypic functions corresponding to the general function of the cluster to which they belong.


Assuntos
Carcinoma Krebs 2 , Células-Tronco Neoplásicas , Humanos , Animais , Camundongos , Células-Tronco Neoplásicas/metabolismo , DNA/metabolismo , Glicoproteínas/metabolismo , Membrana Celular/metabolismo , Carcinoma Krebs 2/patologia , Proteínas de Membrana/metabolismo
9.
BMC Microbiol ; 20(Suppl 2): 349, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33228530

RESUMO

BACKGROUND: The Uzon Caldera is one of the places on our planet with unique geological, ecological, and microbiological characteristics. Uzon oil is the youngest on Earth. Uzon oil has unique composition, with low proportion of heavy fractions and relatively high content of saturated hydrocarbons. Microbial communities of the «oil site¼ have a diverse composition and live at high temperatures (up to 97 °C), significant oscillations of Eh and pH, and high content of sulfur, sulfides, arsenic, antimony, and mercury in water and rocks. RESULTS: The study analyzed the composition, structure and unique genetics characteristics of the microbial communities of the oil site, analyzed the metabolic pathways in the communities. Metabolic pathways of hydrocarbon degradation by microorganisms have been found. The study found statistically significant relationships between geochemical parameters, taxonomic composition and the completeness of metabolic pathways. It was demonstrated that geochemical parameters determine the structure and metabolic potential of microbial communities. CONCLUSIONS: There were statistically significant relationships between geochemical parameters, taxonomic composition, and the completeness of metabolic pathways. It was demonstrated that geochemical parameters define the structure and metabolic potential of microbial communities. Metabolic pathways of hydrocarbon oxidation was found to prevail in the studied communities, which corroborates the hypothesis on abiogenic synthesis of Uzon hydrothermal petroleum.


Assuntos
Archaea/classificação , Bactérias/classificação , Fontes Termais/microbiologia , Hidrocarbonetos/metabolismo , Solo/química , Archaea/genética , Archaea/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodegradação Ambiental , DNA Ribossômico/genética , Fontes Termais/química , Concentração de Íons de Hidrogênio , Redes e Vias Metabólicas , Microbiota , Filogenia , RNA Ribossômico 16S/genética
10.
BMC Genomics ; 19(Suppl 3): 0, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29504899

RESUMO

BACKGROUND: The progress of medicine, science, technology, education, and culture improves, year by year, quality of life and life expectancy of the populace. The modern human has a chance to further improve the quality and duration of his/her life and the lives of his/her loved ones by bringing their lifestyle in line with their sequenced individual genomes. With this in mind, one of genome-based developments at the junction of personalized medicine and bioinformatics will be considered in this work, where we used two Web services: (i) SNP_TATA_Comparator to search for alleles with a single nucleotide polymorphism (SNP) that alters the affinity of TATA-binding protein (TBP) for the TATA boxes of human gene promoters and (ii) PubMed to look for retrospective clinical reviews on changes in physiological indicators of reproductive potential in carriers of these alleles. RESULTS: A total of 126 SNP markers of female reproductive potential, capable of altering the affinity of TBP for gene promoters, were found using the two above-mentioned Web services. For example, 10 candidate SNP markers of thrombosis (e.g., rs563763767) can cause overproduction of coagulation inducers. In pregnant women, Hughes syndrome provokes thrombosis with a fatal outcome although this syndrome can be diagnosed and eliminated even at the earliest stages of its development. Thus, in women carrying any of the above SNPs, preventive treatment of this syndrome before a planned pregnancy can reduce the risk of death. Similarly, seven SNP markers predicted here (e.g., rs774688955) can elevate the risk of myocardial infarction. In line with Bowles' lifespan theory, women carrying any of these SNPs may modify their lifestyle to improve their longevity if they can take under advisement that risks of myocardial infarction increase with age of the mother, total number of pregnancies, in multiple pregnancies, pregnancies under the age of 20, hypertension, preeclampsia, menstrual cycle irregularity, and in women smokers. CONCLUSIONS: According to Bowles' lifespan theory-which links reproductive potential, quality of life, and life expectancy-the above information was compiled for those who would like to reduce risks of diseases corresponding to alleles in own sequenced genomes. Candidate SNP markers can focus the clinical analysis of unannotated SNPs, after which they may become useful for people who would like to bring their lifestyle in line with their sequenced individual genomes.


Assuntos
Marcadores Genéticos/genética , Genômica , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Reprodução/genética , Proteína de Ligação a TATA-Box/metabolismo , Linhagem Celular , Feminino , Humanos , Internet , Ligação Proteica
11.
BMC Genomics ; 17(Suppl 14): 995, 2016 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-28105927

RESUMO

BACKGROUND: Aggressiveness in humans is a hereditary behavioral trait that mobilizes all systems of the body-first of all, the nervous and endocrine systems, and then the respiratory, vascular, muscular, and others-e.g., for the defense of oneself, children, family, shelter, territory, and other possessions as well as personal interests. The level of aggressiveness of a person determines many other characteristics of quality of life and lifespan, acting as a stress factor. Aggressive behavior depends on many parameters such as age, gender, diseases and treatment, diet, and environmental conditions. Among them, genetic factors are believed to be the main parameters that are well-studied at the factual level, but in actuality, genome-wide studies of aggressive behavior appeared relatively recently. One of the biggest projects of the modern science-1000 Genomes-involves identification of single nucleotide polymorphisms (SNPs), i.e., differences of individual genomes from the reference genome. SNPs can be associated with hereditary diseases, their complications, comorbidities, and responses to stress or a drug. Clinical comparisons between cohorts of patients and healthy volunteers (as a control) allow for identifying SNPs whose allele frequencies significantly separate them from one another as markers of the above conditions. Computer-based preliminary analysis of millions of SNPs detected by the 1000 Genomes project can accelerate clinical search for SNP markers due to preliminary whole-genome search for the most meaningful candidate SNP markers and discarding of neutral and poorly substantiated SNPs. RESULTS: Here, we combine two computer-based search methods for SNPs (that alter gene expression) {i} Web service SNP_TATA_Comparator (DNA sequence analysis) and {ii} PubMed-based manual search for articles on aggressiveness using heuristic keywords. Near the known binding sites for TATA-binding protein (TBP) in human gene promoters, we found aggressiveness-related candidate SNP markers, including rs1143627 (associated with higher aggressiveness in patients undergoing cytokine immunotherapy), rs544850971 (higher aggressiveness in old women taking lipid-lowering medication), and rs10895068 (childhood aggressiveness-related obesity in adolescence with cardiovascular complications in adulthood). CONCLUSIONS: After validation of these candidate markers by clinical protocols, these SNPs may become useful for physicians (may help to improve treatment of patients) and for the general population (a lifestyle choice preventing aggressiveness-related complications).


Assuntos
Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteína de Ligação a TATA-Box/metabolismo , Alelos , Progressão da Doença , Feminino , Estudos de Associação Genética , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/patologia , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Obesidade/complicações , Obesidade/genética , Fenótipo , Prognóstico , Ligação Proteica , Resultado do Tratamento
12.
BMC Genet ; 17(Suppl 3): 158, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-28105929

RESUMO

BACKGROUND: Obesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation. RESULTS: The compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein-coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). CONCLUSIONS: A compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity.


Assuntos
Encéfalo/metabolismo , Comportamento Alimentar/fisiologia , Estudo de Associação Genômica Ampla , Peso Corporal , Bases de Dados Factuais , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas/genética
13.
BMC Genomics ; 16 Suppl 13: S3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26693857

RESUMO

BACKGROUND: An important issue in the target identification for the drug design is the tissue-specific effect of inhibition of target genes. The task of assessing the tissue-specific effect in suppressing gene activity is especially relevant in the studies of the brain, because a significant variability in gene expression levels among different areas of the brain was well documented. RESULTS: A method is proposed for constructing statistical models to predict the potential effect of the knockout of target genes on the expression of genes involved in the regulation of apoptosis in various brain regions. The model connects the expression of the objective group of genes with expression of the target gene by means of machine learning models trained on available expression data. Information about the interactions between target and objective genes is determined by reconstruction of target-centric gene network. STRING and ANDSystem databases are used for the reconstruction of gene networks. The developed models have been used to analyse gene knockout effects of more than 7,500 target genes on the expression of 1,900 objective genes associated with the Gene Ontology category "apoptotic process". The tissue-specific effect was calculated for 12 main anatomical structures of the human brain. Initial values of gene expression in these anatomical structures were taken from the Allen Brain Atlas database. The results of the predictions of the effect of suppressing the activity of target genes on apoptosis, calculated on average for all brain structures, were in good agreement with experimental data on siRNA-inhibition. CONCLUSIONS: This theoretical paper presents an approach that can be used to assess tissue-specific gene knockout effect on gene expression of the studied biological process in various structures of the brain. Genes that, according to the predictions of the model, have the highest values of tissue-specific effects on the apoptosis network can be considered as potential pharmacological targets for the development of drugs that would potentially have strong effect on the specific area of the brain and a much weaker effect on other brain structures. Further experiments should be provided in order to confirm the potential findings of the method.


Assuntos
Apoptose/genética , Encéfalo/metabolismo , Técnicas de Inativação de Genes , Modelos Estatísticos , Especificidade de Órgãos/genética , Encéfalo/anatomia & histologia , Biologia Computacional/métodos , Humanos , Modelos Genéticos
14.
BMC Genomics ; 16 Suppl 13: S4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26693966

RESUMO

BACKGROUND: As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain. RESULTS: A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development. CONCLUSIONS: Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.


Assuntos
Encéfalo/embriologia , Evolução Molecular , Regulação da Expressão Gênica , Hominidae/genética , MicroRNAs/genética , RNA Mensageiro/genética , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Humanos , Recém-Nascido , Pan troglodytes
15.
BMC Genomics ; 16 Suppl 13: S5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26694100

RESUMO

BACKGROUND: Obesity affects quality of life and life expectancy and is associated with cardiovascular disorders, cancer, diabetes, reproductive disorders in women, prostate diseases in men, and congenital anomalies in children. The use of single nucleotide polymorphism (SNP) markers of diseases and drug responses (i.e., significant differences of personal genomes of patients from the reference human genome) can help physicians to improve treatment. Clinical research can validate SNP markers via genotyping of patients and demonstration that SNP alleles are significantly more frequent in patients than in healthy people. The search for biomedical SNP markers of interest can be accelerated by computer-based analysis of hundreds of millions of SNPs in the 1000 Genomes project because of selection of the most meaningful candidate SNP markers and elimination of neutral SNPs. RESULTS: We cross-validated the output of two computer-based methods: DNA sequence analysis using Web service SNP_TATA_Comparator and keyword search for articles on comorbidities of obesity. Near the sites binding to TATA-binding protein (TBP) in human gene promoters, we found 22 obesity-related candidate SNP markers, including rs10895068 (male breast cancer in obesity); rs35036378 (reduced risk of obesity after ovariectomy); rs201739205 (reduced risk of obesity-related cancers due to weight loss by diet/exercise in obese postmenopausal women); rs183433761 (obesity resistance during a high-fat diet); rs367732974 and rs549591993 (both: cardiovascular complications in obese patients with type 2 diabetes mellitus); rs200487063 and rs34104384 (both: obesity-caused hypertension); rs35518301, rs72661131, and rs562962093 (all: obesity); and rs397509430, rs33980857, rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, and rs34166473 (all: chronic inflammation in comorbidities of obesity). Using an electrophoretic mobility shift assay under nonequilibrium conditions, we empirically validated the statistical significance (α < 0.00025) of the differences in TBP affinity values between the minor and ancestral alleles of 4 out of the 22 SNPs: rs200487063, rs201381696, rs34104384, and rs183433761. We also measured half-life (t1/2), Gibbs free energy change (ΔG), and the association and dissociation rate constants, ka and kd, of the TBP-DNA complex for these SNPs. CONCLUSIONS: Validation of the 22 candidate SNP markers by proper clinical protocols appears to have a strong rationale and may advance postgenomic predictive preventive personalized medicine.


Assuntos
Obesidade/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteína de Ligação a TATA-Box/química , Proteína de Ligação a TATA-Box/metabolismo , Marcadores Genéticos , Humanos , Obesidade/metabolismo
16.
Alcohol Clin Exp Res ; 39(7): 1128-36, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26058418

RESUMO

BACKGROUND: The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals. METHODS: The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague-Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy ((1) H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia. RESULTS: Partial least squares discriminant analysis processing of the brain (1) H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract. CONCLUSIONS: Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension.


Assuntos
Transtornos Relacionados ao Uso de Álcool/prevenção & controle , Produtos Biológicos/uso terapêutico , Reishi , Consumo de Bebidas Alcoólicas/sangue , Animais , Produtos Biológicos/farmacologia , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Hepatócitos/efeitos dos fármacos , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Ratos Sprague-Dawley
19.
BMC Genomics ; 15 Suppl 12: S11, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25563301

RESUMO

BACKGROUND: Long-range chromatin interactions play an important role in transcription regulation. Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET) is an emerging technology that has unique advantages in chromatin interaction analysis, and thus provides insight into the study of transcription regulation. RESULTS: This article introduces the experimental protocol and data analysis process of ChIA-PET, as well as discusses some applications using this technology. It also unveils the direction of future studies based on this technology. CONCLUSIONS: Overall we show that ChIA-PET is the cornerstone to explore the three-dimensional (3D) chromatin structure, and certainly will lead the forthcoming wave of 3D genomics studies.


Assuntos
Cromatina/química , Cromatina/metabolismo , Análise de Sequência de DNA/métodos , Transcrição Gênica , Genômica , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo
20.
BMC Genomics ; 15 Suppl 12: S12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25563397

RESUMO

BACKGROUND: Geothermal areas are of great interest for the study of microbial communities. The results of such investigations can be used in a variety of fields (ecology, microbiology, medicine) to answer fundamental questions, as well as those with practical benefits. Uzon caldera is located in the Uzon-Geyser depression that is situated in the centre of the Karym-Semyachin region of the East Kamchatka graben-synclinorium. The microbial communities of Zavarzin spring are well studied; however, its benthic microbial mat has not been previously described. RESULTS: Pyrosequencing of the V3 region of the 16S rRNA gene was used to study the benthic microbial community of the Zavarzin thermal spring (Uzon Caldera, Kamchatka). The community is dominated by bacteria (>95% of all sequences), including thermophilic, chemoorganotrophic Caldiserica (33.0%) and Dictyoglomi (24.8%). The benthic community and the previously examined planktonic community of Zavarzin spring have qualitatively similar, but quantitatively different, compositions. CONCLUSIONS: In this study, we performed a metagenomic analysis of the benthic microbial mat of Zavarzin spring. We compared this benthic community to microbial communities found in the water and of an integral probe consisting of water and bottom sediments. Various phylogenetic groups of microorganisms, including potentially new ones, represent the full-fledged trophic system of Zavarzin. A thorough geochemical study of the spring was performed.


Assuntos
Fontes Termais/microbiologia , Metagenoma , Archaea/classificação , Archaea/genética , Archaea/isolamento & purificação , Archaea/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Elementos Químicos , Sedimentos Geológicos/química , Fontes Termais/análise , Fontes Termais/química , Minerais/análise , Federação Russa
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