Navegando por Palavras-chave "gene"

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    Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls
    (Assoc Brasileira Psiquiatria, 2017) Matsuzaka, Camila T. [UNIFESP]; Christofolini, Denise; Ota, Vanessa K. [UNIFESP]; Gadelha, Ary [UNIFESP]; Berberian, Arthur A. [UNIFESP]; Noto, Cristiano [UNIFESP]; Mazzotti, Diego R. [UNIFESP]; Spindola, Leticia M. [UNIFESP]; Moretti, Patricia N. [UNIFESP]; Smith, Marilia A. C. [UNIFESP]; Melaragno, Maria I. [UNIFESP]; Belangero, Sintia I. [UNIFESP]; Bressan, Rodrigo A. [UNIFESP]
    Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype* group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.
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    Epilepsy research 150 years after Darwin's theory of evolution
    (Academia Brasileira de Neurologia - ABNEURO, 2009-12-01) Scorza, Fulvio Alexandre [UNIFESP]; Terra, Vera Cristina; Scorza, Carla Alessandra [UNIFESP]; Arida, Ricardo Mario [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    On February 12, 2009, we commemorated the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of the ûrst edition of the On the origin of species. Only in the sixth edition of the Origin Darwin explicitly stated that natural selection applied to the brain as to all other organs and contemporary epilepsy research plays an interesting role in this scenario. Epilepsy affects approximately 3 percent of the general population and is a complex disease. At least 11 genes have now been described for human epilepsy and over 50 more genes have been identified in animal models of epilepsy. The complex gene to gene interactions and gene-environment interactions may account for epilepsy susceptibility and antiepileptic drug response. Darwin's thoughts on evolution are relevant to understand these gene interactions, contributing to current development of new treatments and prevention of chronic diseases, such as epilepsy.
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    Estudos de associação genética no transtorno obsessivo-compulsivo
    (Faculdade de Medicina da Universidade de São Paulo, 2013-01-01) Sampaio, Aline Santos; Lins, Rita Márcia Pacheco; Daltro-Oliveira, Renato; Quarantini, Lucas de Castro [UNIFESP]; Rosario-Campos, Maria Conceicao do [UNIFESP]; Miguel, Euripedes Constantino; Hounie, Ana Gabriela; Universidade de São Paulo (USP); Universidade Federal da Bahia Serviço Médico Universitário Dr. Rubens Brasil; UFBA Faculdade de Medicina Departamento de Neurociências e Saúde Mental; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: Obsessive-compulsive disorder (OCD) segregates in families. It follows a complex model of genetic transmission, which involves the influence of several small effect genes interacting with the environment. METHODS: A systematic review of genetic association studies in OCD was performed. Articles published until 2012 were searched in the databases PubMed, Embase and SciELO using the terms of MeSH and its associates or synonyms for obsessive-compulsive disorder, gene and genetic association studies. RESULTS: We selected 105 papers and described their main results grouped as genes related to: serotonin, dopamine, glutamate, GABA, white matter, immune system, hormones and other genes. CONCLUSION: There is high variability between findings of association studies among the several candidate genes studied in OCD. Glutamate-related genes are promising candidates for OCD, but there is no conclusive association between any of the candidate genes studied and OCD. Association studies with large sample size, evaluation of more homogeneous subgroups of phenotype and meta-analyses are still needed.
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    Influence of ovarian hormones deprivation on gene expression in the lower urinary tract of rats
    (Sociedade Brasileira de Urologia, 2007-08-01) Bortolini, Maria Augusta Tezelli [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Hamerski, Maria G. [UNIFESP]; Castro, Rodrigo de Aquino [UNIFESP]; Sartori, Marair Gracio Ferreira [UNIFESP]; Girão, Manoel João Batista Castello [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    OBJECTIVE: Identify the influence of ovarian hormone deprivation in expression genes on the lower urinary tract of rats. MATERIALS AND METHODS: This study deals with gene screening on lower urinary tract of rats. Fifty isogenic rats divided in two groups of twenty-five animals have their lower urinary tract surgically removed: group I, ovariectomized rats 30 days prior to surgery; group II, non-ovariectomized rats. Total RNA was isolated from bladder and urethra, and differential expression of genes was analyzed quantitative, qualitative and comparatively by array technology and RT-PCR. RESULTS: A total of 76 candidate genes were identified as differentially expressed between the groups, 26 being lower expressed in group II, and 50 in group I. Among them, differential expression validation was confirmed by RT-PCR for three lower expressed genes in group I: Vascular Endothelial Growth Factor (VEGF), Beta-2 Microglobulin (B2M) and Cytochrome c Oxidase subunit I (COX I). CONCLUSION: Ovarian hormone deprivation influences the expression genes on lower urinary tract. We demonstrated that a 30-day period of castration down regulate the expression of VEGF, B2M and COX I in adult rats which are involved in activities of angiogenesis, immune responses and cellular metabolism respectively.
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    Kunitz-type Bauhinia bauhinioides inhibitors devoid of disulfide bridges: isolation of the cDNAs, heterologous expression and structural studies
    (Walter de Gruyter & Co, 2005-06-01) Araujo, APU; Hansen, D.; Vieira, D. F.; Oliveira, C. de; Santana, L. A.; Beltramini, L. M.; Sampaio, CAM; Sampaio, M. U.; Oliva, MLV; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Bauhinia bauhinoides cruzipain inhibitor (BbCl) and Bauhinia bauhinioides kallikrein inhibitor (BbKl) are cysteine and serine proteinase inhibitors structurally homologous to plant Kunitz-type inhibitors, but are devoid of disulfide bridges. Based on cDNA sequences, we found that BbKI and BbCI are initially synthesized as a prepropepticle comprising an N-terminal signal peptide (19 residues), the mature protein (164 residues) and a C-terminal targeting peptide (10 residues). Partial cDNAs encoding the mature enzymes plus N-terminal His-tags and thrombin cleavage sites were expressed in E coli and the soluble proteins were purified by one-step nickel affinity chromatography. After thrombin cleavage, both proteins exhibited potent inhibitory activities toward their cognate proteinases like the wild-type proteins. BbCl inhibits human neutrophil elastase (K-i(app) 5.3 nM), porcine pancreatic elastase (K-i(app) 40 nM), cathepsin G (K-i(app) 160 nM) and the cysteine proteinases cruzipain (K-i(app) 1.2 nM), cruzain (K-i(app) 0.3 nM) and cathepsin L (K-i(app) 2.2 nM), while BbKl strongly inhibits plasma kallikrein (K-i(app) 2.4 nM) and plasmin (K-i(app) 33 nM). Circular dichroism spectra of BbCl and BbKl were in agreement with the P-trefoil fold described for Kunitz inhibitors. the inhibitory potency of both BbCl- and BbKl-type inhibitors suggests that other, non-covalent interactions may compensate for the lack of disulficle bridges.
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    The largest subunit of the RNA polymerase II of Trypanosoma cruzi lacks the repeats in the carboxy-terminal domain and is encoded by several genes
    (Elsevier B.V., 2003-09-01) Ejchel, Tatiana Flank [UNIFESP]; Ramirez, M. I.; Vargas, N.; Azevedo, E. B.; Elias, M. C.; Zingales, B.; Schenkman, S.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    The largest subunit of eukaryotic RNA polymerase II (RNA Pol II) of several members of Kinetoplastida order and other early diverging eukaryote contains a serine, tyrosine and proline-rich domain in the carboxyl-terminal instead of the typical heptapeptides repeats found in most eukaryotes. the lack of these repeats seems to reflect the different control of gene transcription found in these organisms. To provide further understanding in these mechanisms, we have characterized the largest subunit of RNA polymerase II (RNA Pol II LSU) in Trypanosoma cruzi. We found that it also lacks the heptapeptide repeats in the carboxy-terminal domain, but is quite similar to, the same region in the Trypanosoma brucei enzyme, suggesting a conserved role for this domain. in addition, we found several genes encoding the RNA Pol II in T cruzi, distributed in different chromosomal bands in several isolates. Two of these genes were entirely sequenced and shown to be quite similar. the presence of several gene copies of the RNA Pol II LSU, also described in African trypanosomes might reflect a gene amplification requirement that appeared early in the evolution of these organisms. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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    Organization of trans-sialidase genes in Trypanosoma cruzi
    (Elsevier B.V., 1996-05-01) Egima, C. M.; Briones, MRS; Freitas, LHG; Schenkman, RPF; Uemura, H.; Schenkman, S.; Universidade Federal de São Paulo (UNIFESP); NAGASAKI UNIV
    Trypanosoma cruzi trans-sialidase is encoded by a family of genes containing a conserved region, which corresponds to the catalytic and amino-terminal domain of the enzyme. Most, but not all genes, also encode a variable region formed by 12 amino acid repeats at the carboxy-terminus of the protein that are not required for enzymatic activity. To design gene knock-out strategies and understand how trans-sialidase expression is regulated, we have studied the genome organization of trans-sialidase genes. We show here that the different types of trans-sialidase genes are distributed in more than one chromosomal band with sizes ranging from 0.8 to 1.5 Mb pairs in several T. cruzi strains. in the Y-strain, all repeat-containing genes are localized in one chromosomal band of 1.1 Mb, while the repeat-minus genes are in two chromosomes of 0.82 and 0.79 Mb. the repeat-containing genes have similar catalytic and intergenic regions, but variable lengths of the repeated region. the trans-sialidase genes with the repeats are in tandem of up to 12 genes in at least four different clusters. Each cluster contains genes with different numbers of repeats, according to the physical maps of eight independent cosmids, and in the same cluster there are genes that code for active and inactive trans-sialidases. There are 80 +/- 30 copies of the repeat-containing genes grouped in two NotI fragments of 120 and 180 Kb. Therefore, in the Y-strain, the trans-sialidase genes containing repeats might be arranged in three to four clusters in two homologous chromosomes, each cluster having up to 12 genes with different repeat numbers.
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    The role of the CNR1 gene in schizophrenia: a systematic review including unpublished data
    (Assoc Brasileira Psiquiatria, 2017) Gouvea, Eduardo S. [UNIFESP]; Santos Filho, Airton F. [UNIFESP]; Ota, Vanessa K. [UNIFESP]; Mrad, Vinicius [UNIFESP]; Gadelha, Ary [UNIFESP]; Bressan, Rodrigo A. [UNIFESP]; Cordeiro, Quirino [UNIFESP]; Belangero, Sintia I. [UNIFESP]
    Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population. Methods: Two reviewers independently searched for eligible studies and extracted outcome data using a structured form. Papers were retrieved from PubMed and ISI Web of Knowledge using the search term schizophrenia in combination with CNR1 or CB1 or cannabinoid receptor. Twenty-four articles met our inclusion criteria. We additionally present data from a study of our own comparing 182 patients with schizophrenia and 244 healthy controls. Results: No consistent evidence is demonstrated. Conclusion: Some seemingly positive association studies stress the need for further investigations of the possible role of endocannabinoid genetics in schizophrenia.
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    Single-nucleotide polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis as risk factors for posttraumatic stress disorder
    (Wiley, 2017) Carvalho, Carolina M [UNIFESP].; Coimbra, Bruno M. [UNIFESP]; Ota, Vanessa K. [UNIFESP]; Mello, Marcelo F. [UNIFESP]; Belangero, Sintia I. [UNIFESP]
    Posttraumatic stress disorder (PTSD) is a common psychiatric disorder. The etiology of PTSD is multifactorial, depending on many environmental and genetic risk factors, and the exposure to life or physical integrity-threatening events. Several studies have shown significant correlations of many neurobiological findings with PTSD. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is strongly correlated with this disorder. One hypothesis is that HPA axis dysfunction may precede the traumatic event, suggesting that genes expressed in the HPA axis may be involved in the development of PTSD. This article reviews molecular genetic studies related to PTSD collected through a literature search performed in PubMed, MEDLINE, ScienceDirect, and Scientific Electronic Library Online (SciELO). The results of these studies suggest that several polymorphisms in the HPA axis genes, including FKBP5, NR3C1, CRHR1, and CRHR2, may be risk factors for PTSD development or may be associated with the severity of PTSD symptoms.
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    SmPKC1, a new protein kinase C identified in the platyhelminth parasite Schistosoma mansoni
    (Elsevier B.V., 2006-07-07) Bahia, Diana; Avelar, Livia; Mortara, Renato A.; Khayath, Naji; Yan, Yutao; Noel, Christophe; Capron, Monique; Dissous, Colette; Pierce, Raymond J.; Oliveira, Guilherme; Inst Pasteur; Fiocruz MS; Universidade Federal de São Paulo (UNIFESP); Newcastle Univ; Santa Casa Misericordia Belo Horizonte
    Schistosoma mansoni signal transduction pathways are promising sources of target molecules for the development of novel control strategies against this platyhelminth parasite of humans. Members of the protein kinase C (PKC) family play key roles in such pathways activated by both receptor tyrosine kinases and other receptors, controlling a variety of physiological processes. Here, we report the cloning and molecular characterization of the first PKC identified in S. mansoni. Structural analysis indicated that SmPKC1 exhibits all the features typical of the conventional PKC subfamily. the gene structure was determined in silico and found to comprise a total of 15 exons and 14 introns. This structure is highly conserved; all intron positions are also present in the human PKC beta gene and most of the exon sizes are identical. Using PCR on genomic DNA we were able to show that putative orthologues of SmPKC1 are present in 9 Schistosoma species. SmPKC1 expression is developmentally regulated with the highest level of transcripts in miracidia, whereas SmPKC1 protein expression is higher in the sporocyst. the localization of SmPKC1 on the sporocyst ridge cyton and in schistosomula acetabular glands suggests that the enzyme plays a role in signal transduction pathways associated with larval transformation. (c) 2006 Elsevier Inc. All rights reserved.
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    Structure of the mammalian kinin receptor gene locus
    (Elsevier B.V., 2002-12-01) Cecile, C. A.; Merino, Vanessa Ferreira [UNIFESP]; Cabrini, D. A.; Silva, J. A.; Pesquero, João Bosco [UNIFESP]; Bader, Michael [UNIFESP]; Max Delbruck Ctr Mol Med; Universidade Federal de São Paulo (UNIFESP)
    The genes encoding the two kinin receptors, B1 and B2, are closely linked on the same chromosome in human, mouse, and rat. In this article, we present the organisation of the B1B2 locus in these mammals. This organisation was obtained by comparing the kinin receptor mRNA sequences of man and mouse with the sequence of chromosomes 14 and 12, respectively. We found that the two genes are located in tandem orientation, separated by only 7.8 kb in mice and 12 kb in humans. The distance of the two genes on rat chromosome 6 was determined by long-range PCR to be 9.5 kb. The organisation of the two genes encoding the kinin receptors is similar in the three species, except that the human B1 gene harbors an additional exon, which may originate from the insertion of an Alu repetitive sequence during evolution. Moreover, the human and rat, but not the murine, B2 genes carry an alternatively spliced exon between exons 2 and 3, termed exon 2b. (C) 2002 Elsevier Science B.V. All rights reserved.