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[PMID]: 28961413 [Au] Autor: Faust TB; Binning JM; Gross JD; Frankel AD [Ad] Endereço: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158; email: tybifa@gmail.com , frankel@cgl.ucsf.edu. [Ti] Título: Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription. [So] Source: Annu Rev Virol;4(1):241-260, 2017 Sep 29. [Is] ISSN: 2327-0578 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Viruses are completely dependent upon cellular machinery to support replication and have therefore developed strategies to co-opt cellular processes to optimize infection and counter host immune defenses. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode a relatively small number of genes. Viruses with limited genetic content often encode multifunctional proteins that function at multiple stages of the viral replication cycle. In this review, we discuss the functions of HIV-1 regulatory (Tat and Rev) and accessory (Vif, Vpr, Vpu, and Nef) proteins. Each of these proteins has a highly conserved primary activity; however, numerous additional activities have been attributed to these viral proteins. We explore the possibility that HIV-1 proteins leverage their multifunctional nature to alter host transcriptional networks to elicit a diverse set of cellular responses. Although these transcriptional effects appear to benefit the virus, it is not yet clear whether they are strongly selected for during viral evolution or are a ripple effect from the primary function. As our detailed knowledge of these viral proteins improves, we will undoubtedly uncover how the multifunctional nature of these HIV-1 regulatory and accessory proteins, and in particular their transcriptional functions, work to drive viral pathogenesis. [Mh] Termos MeSH primário: Genes rev Genes tat HIV-1/genética Proteínas do Vírus da Imunodeficiência Humana/metabolismo Transcrição Genética Proteínas Virais Reguladoras e Acessórias/metabolismo [Mh] Termos MeSH secundário: HIV-1/química HIV-1/fisiologia Interações Hospedeiro-Patógeno Proteínas do Vírus da Imunodeficiência Humana/genética Seres Humanos Proteínas Virais Reguladoras e Acessórias/genética Replicação Viral Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo Produtos do Gene vpr do Vírus da Imunodeficiência Humana/genética Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Human Immunodeficiency Virus Proteins); 0 (Viral Regulatory and Accessory Proteins); 0 (nef Gene Products, Human Immunodeficiency Virus); 0 (vif Gene Products, Human Immunodeficiency Virus); 0 (vpr Gene Products, Human Immunodeficiency Virus); 0 (vpu protein, Human immunodeficiency virus 1) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171027 [Lr] Data última revisão: 171027 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170930 [St] Status: MEDLINE [do] DOI: 10.1146/annurev-virology-101416-041654

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[PMID]: 26502640 [Au] Autor: Li F; Wang Z; Huang Y; Xu H; He L; Deng Yan; Zeng X; He N [Ti] Título: Delivery of PUMA Apoptosis Gene Using Polyethyleneimine-SMCC-TAT/DNA Nanoparticles: Biophysical Characterization and In Vitro Transfection Into Malignant Melanoma Cells. [So] Source: J Biomed Nanotechnol;11(10):1776-82, 2015 Oct. [Is] ISSN: 1550-7033 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: A synthesized PEI-based gene delivery system, wherein PEI was crosslinked with sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC) conjugating trans-activating transcriptional activator (TAT), yielding PEI-SMCC-TAT (PST), a novel non-viral vector for apoptosis-related gene PUMA (p53 up regulated modulator of apoptosis), was designed and evaluated. Sulfo-SMCC is a commonly used heterobifunctional crosslinker and is soluble in water, making the crosslinking easier without organic reagent like DMSO or chloroform. The PST/pDNA nanoparticles were 171.9 nm at the optimal N/P ratio (50:1). DNA complexes of all the PST conjugation had much lower toxicity and exhibited enhancement in transfection efficiency in comparison with single PEI vector. The results also showed that the transfection efficiency of PST/pEGFP nanoparticles into malignant melanoma A375 cell increased, and PST carrying PUMA gene induced the apoptosis of A375 cells. It was suggested that PST could be a promising melanoma tumor-targeting nanovector, and have a good potential in clinical application. [Mh] Termos MeSH primário: Genes tat/genética Melanoma/genética Melanoma/terapia Nanocápsulas/química Polietilenoimina/química Transfecção/métodos [Mh] Termos MeSH secundário: Apoptose/genética Linhagem Celular Tumoral Difusão Seres Humanos Maleimidas/química Melanoma/patologia Nanocápsulas/administração & dosagem Nanocápsulas/ultraestrutura Tamanho da Partícula Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Maleimides); 0 (Nanocapsules); 64987-85-5 (N-(4-carboxycyclohexylmethyl)maleimide N-hydroxysuccinimide ester); 9002-98-6 (Polyethyleneimine) [Em] Mês de entrada: 1511 [Cu] Atualização por classe: 151027 [Lr] Data última revisão: 151027 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 151028 [St] Status: MEDLINE

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[PMID]: 24813724 [Au] Autor: Silva JN; Polesskaya O; Wei HS; Rasheed IY; Chamberlain JM; Nishimura C; Feng C; Dewhurst S [Ad] Endereço: Departments of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA. [Ti] Título: Chronic central nervous system expression of HIV-1 Tat leads to accelerated rarefaction of neocortical capillaries and loss of red blood cell velocity heterogeneity. [So] Source: Microcirculation;21(7):664-76, 2014 Oct. [Is] ISSN: 1549-8719 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVES: HIV-1 infection of the CNS is associated with impairment of CBF and neurocognitive function, and accelerated signs of aging. As normal aging is associated with rarefaction of the cerebral vasculature, we set out to examine chronic viral effects on the cerebral vasculature. METHODS: DOX-inducible HIV-1 Tat-tg and WT control mice were used. Animals were treated with DOX for three weeks or five to seven months. Cerebral vessel density and capillary segment length were determined from quantitative image analyses of sectioned cortical tissue. In addition, movement of red blood cells in individual capillaries was imaged in vivo using multiphoton microscopy, to determine RBCV and flux. RESULTS: Mean RBCV was not different between Tat-tg mice and age-matched WT controls. However, cortical capillaries from Tat-tg mice showed a significant loss of RBCV heterogeneity and increased RBCF that was attributed to a marked decrease in total cortical capillary length (35-40%) compared to WT mice. CONCLUSIONS: Cerebrovascular rarefaction is accelerated in HIV-1 Tat-transgenic mice, and this is associated with alterations in red cell blood velocity. These changes may have relevance to the pathogenesis of HIV-associated neurocognitive disorders in an aging HIV-positive population. [Mh] Termos MeSH primário: Velocidade do Fluxo Sanguíneo Genes tat HIV-1/genética Neocórtex/irrigação sanguínea Produtos do Gene tat do Vírus da Imunodeficiência Humana/toxicidade [Mh] Termos MeSH secundário: Animais Astrócitos/metabolismo Capilares/patologia Doxiciclina/farmacologia Índices de Eritrócitos Hemodinâmica Masculino Camundongos Camundongos Transgênicos Microscopia de Fluorescência por Excitação Multifotônica Neovascularização Fisiológica/efeitos dos fármacos Células Piramidais/patologia Proteínas Recombinantes de Fusão/toxicidade Regulação para Cima/efeitos dos fármacos Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Recombinant Fusion Proteins); 0 (tat Gene Products, Human Immunodeficiency Virus); N12000U13O (Doxycycline) [Em] Mês de entrada: 1506 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 140513 [St] Status: MEDLINE [do] DOI: 10.1111/micc.12145

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[PMID]: 24625401 [Au] Autor: Zhao L; Pu SS; Gao WH; Chi YY; Wen HL; Wang ZY; Song YY; Yu XJ [Ad] Endereço: Department of Laboratory Microbiology, School of Public Health, Shandong University, Jinan 250012, Shandong, China. [Ti] Título: Effects of HIV-1 tat on secretion of TNF-α and IL-1ß by U87 cells in AIDS patients with or without AIDS dementia complex. [So] Source: Biomed Environ Sci;27(2):111-7, 2014 Feb. [Is] ISSN: 0895-3988 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To explore the role of HIV-1 tat gene variations in AIDS dementia complex (ADC) pathogenesis. METHODS: HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1ß concentrations in the supernatant of U87 cells were determined with ELISA. RESULTS: HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area (38-47aa). All Tat proteins could induce U87 cells to produce TNF-α and IL-1ß, but the level of IL-1ß production was different among Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen. The level of Tat proteins derived from the ADC patient's spleen, basal ganglia, and the non-ADC patient's spleen were obviously higher than that from the non-ADC patient's basal ganglia. CONCLUSION: Tat protein core functional area (38-47aa) may serve as the key area of enhancing the secretion of IL-1ß. This may be related with the neurotoxicity of HIV-1 Tat. [Mh] Termos MeSH primário: Complexo AIDS Demência/metabolismo Complexo AIDS Demência/virologia Genes tat HIV-1/patogenicidade Interleucina-1beta/secreção Neuroglia/secreção Fator de Necrose Tumoral alfa/secreção Produtos do Gene tat do Vírus da Imunodeficiência Humana/fisiologia [Mh] Termos MeSH secundário: Complexo AIDS Demência/patologia Adulto Sequência de Aminoácidos Gânglios da Base/virologia Linhagem Celular Tumoral Regulação Viral da Expressão Gênica HIV-1/genética Seres Humanos Interleucina-1beta/biossíntese Interleucina-1beta/genética Meia-Idade Dados de Sequência Molecular Neuroglia/patologia Baço/virologia Fator de Necrose Tumoral alfa/biossíntese Fator de Necrose Tumoral alfa/genética Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Interleukin-1beta); 0 (Tumor Necrosis Factor-alpha); 0 (tat Gene Products, Human Immunodeficiency Virus) [Em] Mês de entrada: 1406 [Cu] Atualização por classe: 140314 [Lr] Data última revisão: 140314 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 140315 [St] Status: MEDLINE [do] DOI: 10.3967/bes2014.024

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[PMID]: 23962166 [Au] Autor: Katas H; Abdul Ghafoor Raja M; Ee LC [Ad] Endereço: Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia , Jalan Raja Muda Abdul Aziz, Kuala Lumpur , Malaysia. [Ti] Título: Comparative characterization and cytotoxicity study of TAT-peptide as potential vectors for siRNA and Dicer-substrate siRNA. [So] Source: Drug Dev Ind Pharm;40(11):1443-50, 2014 Nov. [Is] ISSN: 1520-5762 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Recently, a newly discovered Dicer-substrate siRNA (DsiRNA) demonstrates higher potency in gene silencing than siRNA but both suffer from rapid degradation, poor cellular uptake and chemical instability. Therefore, Tat-peptide was exploited to protect and facilitate their delivery into cells. In this study, Tat-peptide was complexed with siRNA or DsiRNA through simple complexation. The physicochemical properties (particle size, surface charge and morphology) of the complexes formed were then characterized. The ability of Tat-peptide to carry and protect siRNA or DsiRNA was determined by UV-Vis spectrophotometry and serum protection assay, respectively. Cytotoxicity effect of these complexes was assessed in V79 cell line. siRNA-Tat complexes had particle size ranged from 186 ± 17.8 to 375 ± 8.3 nm with surface charge ranged from -9.3 ± 1.0 to +13.5 ± 1.0 mV, depending on the Tat-to-siRNA concentration ratio. As for DsiRNA-Tat complexes, the particle size was smaller than the ones complexed with siRNA, ranging from 176 ± 8.6 to 458 ± 14.7 nm. Their surface charge was in the range of +27.1 ± 3.6 to +38.1 ± 0.9 mV. Both oligonucleotide (ON) species bound strongly to Tat-peptide, forming stable complexes with loading efficiency of more than 86%. These complexes were relatively non cytotoxic as the cell viability of ∼90% was achieved. In conclusion, Tat-peptide has a great potential as siRNA and DsiRNA vector due to the formation of stable complexes with desirable physical characteristics, low toxicity and able to carry high amount of siRNA or DsiRNA. [Mh] Termos MeSH primário: Peptídeos Penetradores de Células Genes tat Oligonucleotídeos/química RNA Interferente Pequeno/administração & dosagem Transfecção/métodos [Mh] Termos MeSH secundário: Sobrevivência Celular Sistemas de Liberação de Medicamentos Inativação Gênica Tamanho da Partícula [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cell-Penetrating Peptides); 0 (Oligonucleotides); 0 (RNA, Small Interfering) [Em] Mês de entrada: 1506 [Cu] Atualização por classe: 141017 [Lr] Data última revisão: 141017 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130822 [St] Status: MEDLINE [do] DOI: 10.3109/03639045.2013.828222

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[PMID]: 24020900 [Au] Autor: Neogi U; Palchaudhuri R; Bommana S; Shet A [Ad] Endereço: 1 Hematology Research Unit , Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India . [Ti] Título: Genetic architecture of HIV type 1 Nef and Tat from HLA-B57-typed long-term survivors in an Indian cohort of perinatally HIV-infected children. [So] Source: AIDS Res Hum Retroviruses;29(12):1613-6, 2013 Dec. [Is] ISSN: 1931-8405 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Human immunodeficiency virus type 1 (HIV-1) viral genes nef and tat play an important role in disease progression. In this study we characterized the Nef and Tat proteins from a group of HLA-B57 typed pediatric perinatally infected long-term survivors (LTS) with ≥10 years of infection. We identified 19 therapy-naive LTS after screening 250 children from an Indian pediatric cohort. Nef and tat amplified from plasma virus showed that all the LTS harbored HIV-1 subtype C. The two B57(+) children showed mutations, deletions, and insertions in experimentally defined B57 epitopes in the virus that are likely to be escape mutants. Only GW12 (GPGVRYPLTFGW) and YY9 (YTPGPGIRY) were conserved, while the remaining 90% (18/20) of the epitopes showed some degree of mutations. The most variable epitopes were RR15, SE15, QP15, KF9, HW9, YT9, and GF15. To our knowledge this is the first study from India in which characterization of Nef and Tat from LTS has led to information on genetic alterations in these genes that are associated with slow disease progression, and can provide an important lead in future studies. [Mh] Termos MeSH primário: Genes nef Genes tat Infecções por HIV/virologia Sobreviventes de Longo Prazo ao HIV HIV-1/genética Antígenos HLA-B/genética Transmissão Vertical de Doença Infecciosa [Mh] Termos MeSH secundário: Sequência de Aminoácidos Sequência de Bases Criança Estudos de Coortes Primers do DNA Feminino Infecções por HIV/transmissão HIV-1/classificação Seres Humanos Índia Masculino Dados de Sequência Molecular Reação em Cadeia da Polimerase Homologia de Sequência de Aminoácidos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (DNA Primers); 0 (HLA-B Antigens); 0 (HLA-B57 antigen) [Em] Mês de entrada: 1407 [Cu] Atualização por classe: 131122 [Lr] Data última revisão: 131122 [Sb] Subgrupo de revista: IM; X [Da] Data de entrada para processamento: 130912 [St] Status: MEDLINE [do] DOI: 10.1089/AID.2013.0195

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[PMID]: 23954227 [Au] Autor: Bouyacoub Y; Zribi H; Azzouz H; Nasrallah F; Abdelaziz RB; Kacem M; Rekaya B; Messaoud O; Romdhane L; Charfeddine C; Bouziri M; Bouziri S; Tebib N; Mokni M; Kaabachi N; Boubaker S; Abdelhak S [Ad] Endereço: Université Tunis El Manar, Institut Pasteur de Tunis, LR11IPT05, Génomique Biomédicale et Oncogénétique, 1002 Tunis,Tunisia; Université de Monastire, Institut Supérieur de Biotechnologie, Monastir 5000, Tunisia. [Ti] Título: Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome. [So] Source: Gene;529(1):45-9, 2013 Oct 15. [Is] ISSN: 1879-0038 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Tyrosinemia type II, also designated as oculocutaneous tyrosinemia or Richner-Hanhart syndrome (RHS), is a very rare autosomal recessive disorder. In the present study, we report clinical features and molecular genetic investigation of the tyrosine aminotransferase (TAT) gene in two young patients, both born to consanguineous unions between first-degree cousins. These two unrelated families originated from Northern and Southern Tunisia. The clinical diagnosis was based on the observation of several complications related to Richner-Hanhart syndrome: recurrent eye redness, tearing and burning pain, photophobia, bilateral pseudodendritic keratitis, an erythematous and painful focal palmo-plantar hyperkeratosis and a mild delay of mental development. The diagnosis was confirmed by biochemical analysis. Sequencing of the TAT gene revealed the presence of a previously reported missense mutation (c.452G>A, p.Cys151Tyr) in a Tunisian family, and a novel G duplication (c.869dupG, p.Trp291Leufs 6). Early diagnosis of RHS and protein-restricted diet are crucial to reduce the risk and the severity of long-term complications of hypertyrosinemia such as intellectual disability. [Mh] Termos MeSH primário: Genes tat Mutação de Sentido Incorreto Tirosinemias/genética [Mh] Termos MeSH secundário: Sequência de Aminoácidos Pré-Escolar Consanguinidade Dieta com Restrição de Proteínas Seres Humanos Lactente Ceratite/complicações Ceratite/genética Masculino Dados de Sequência Molecular Linhagem Conformação Proteica Tunísia Tirosina Transaminase/genética Tirosina Transaminase/metabolismo Tirosinemias/complicações Tirosinemias/diagnóstico [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: EC 2.6.1.5 (Tyrosine Transaminase) [Em] Mês de entrada: 1310 [Cu] Atualização por classe: 130909 [Lr] Data última revisão: 130909 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130820 [St] Status: MEDLINE

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[PMID]: 23804632 [Au] Autor: Donahue DA; Bastarache SM; Sloan RD; Wainberg MA [Ad] Endereço: McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Québec, Canada. [Ti] Título: Latent HIV-1 can be reactivated by cellular superinfection in a Tat-dependent manner, which can lead to the emergence of multidrug-resistant recombinant viruses. [So] Source: J Virol;87(17):9620-32, 2013 Sep. [Is] ISSN: 1098-5514 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The HIV-1 latent reservoir represents an important source of genetic diversity that could contribute to viral evolution and multidrug resistance following latent virus reactivation. This could occur by superinfection of a latently infected cell. We asked whether latent viruses might be reactivated when their host cells are superinfected, and if so, whether they could contribute to the generation of recombinant viruses. Using populations of latently infected Jurkat cells, we found that latent viruses were efficiently reactivated upon superinfection. Pathways leading to latent virus reactivation via superinfection might include gp120-CD4/CXCR4-induced signaling, modulation of the cellular environment by Nef, and/or the activity of Tat produced upon superinfection. Using a range of antiviral compounds and genetic approaches, we show that gp120 and Nef are not required for latent virus reactivation by superinfection, but this process depends on production of functional Tat by the superinfecting virus. In a primary cell model of latency in unstimulated CD4 T cells, superinfection also led to latent virus reactivation. Drug-resistant latent viruses were also reactivated following superinfection in Jurkat cells and were able to undergo recombination with the superinfecting virus. Under drug-selective pressure, this generated multidrug-resistant recombinants that were identified by unique restriction digestion band patterns and by population-level sequencing. During conditions of poor drug adherence, treatment interruption or treatment failure, or in drug-impermeable sanctuary sites, reactivation of latent viruses by superinfection or other means could provide for the emergence or spread of replicatively fit viruses in the face of strong selective pressures. [Mh] Termos MeSH primário: HIV-1/genética HIV-1/fisiologia Vírus Reordenados/genética Vírus Reordenados/fisiologia Produtos do Gene tat do Vírus da Imunodeficiência Humana/fisiologia [Mh] Termos MeSH secundário: Antígenos CD4/fisiologia Linfócitos T CD4-Positivos/imunologia Linfócitos T CD4-Positivos/virologia Farmacorresistência Viral Múltipla/genética Genes tat Variação Genética Células HEK293 Proteína gp120 do Envelope de HIV/fisiologia Infecções por HIV/tratamento farmacológico Infecções por HIV/virologia HIV-1/efeitos dos fármacos Células HeLa Seres Humanos Células Jurkat Vírus Reordenados/efeitos dos fármacos Receptores CXCR4/fisiologia Recombinação Genética Seleção Genética Superinfecção/tratamento farmacológico Superinfecção/virologia Ativação Viral/genética Ativação Viral/fisiologia Latência Viral/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (CD4 Antigens); 0 (CXCR4 protein, human); 0 (HIV Envelope Protein gp120); 0 (Receptors, CXCR4); 0 (gp120 protein, Human immunodeficiency virus 1); 0 (tat Gene Products, Human Immunodeficiency Virus) [Em] Mês de entrada: 1311 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130628 [St] Status: MEDLINE [do] DOI: 10.1128/JVI.01165-13

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[PMID]: 23499847 [Au] Autor: Esclapez J; Zafrilla B; Martínez-Espinosa RM; Bonete MJ [Ad] Endereço: Facultad de Ciencias, Universidad de Alicante, Alicante, Spain. [Ti] Título: Cu-NirK from Haloferax mediterranei as an example of metalloprotein maturation and exportation via Tat system. [So] Source: Biochim Biophys Acta;1834(6):1003-9, 2013 Jun. [Is] ISSN: 0006-3002 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: The green Cu-NirK from Haloferax mediterranei (Cu-NirK) has been expressed, refolded and retrieved as a trimeric enzyme using an expression method developed for halophilic Archaea. This method utilizes Haloferax volcanii as a halophilic host and an expression vector with a constitutive and strong promoter. The enzymatic activity of recombinant Cu-NirK was detected in both cellular fractions (cytoplasmic fraction and membranes) and in the culture media. The characterization of the enzyme isolated from the cytoplasmic fraction as well as the culture media revealed important differences in the primary structure of both forms indicating that Hfx. mediterranei could carry out a maturation and exportation process within the cell before the protein is exported to the S-layer. Several conserved signals found in Cu-NirK from Hfx. mediterranei sequence indicate that these processes are closely related to the Tat system. Furthermore, the N-terminal sequence of the two Cu-NirK subunits constituting different isoforms revealed that translation of this protein could begin at two different points, identifying two possible start codons. The hypothesis proposed in this work for halophilic Cu-NirK processing and exportation via the Tat system represents the first approximation of this mechanism in the Halobacteriaceae family and in Prokarya in general. [Mh] Termos MeSH primário: Genes tat Haloferax mediterranei/genética Haloferax mediterranei/metabolismo Metaloproteínas/genética Metaloproteínas/metabolismo Nitrito Redutases/genética Nitrito Redutases/metabolismo [Mh] Termos MeSH secundário: Sequência de Aminoácidos Haloferax volcanii/genética Haloferax volcanii/metabolismo Modelos Moleculares Dados de Sequência Molecular Filogenia Dobramento de Proteína Isoformas de Proteínas Proteínas Recombinantes/genética Proteínas Recombinantes/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Metalloproteins); 0 (Protein Isoforms); 0 (Recombinant Proteins); EC 1.7.- (Nitrite Reductases); EC 1.7.2.1 (nitrite reductase, copper-containing) [Em] Mês de entrada: 1307 [Cu] Atualização por classe: 161126 [Lr] Data última revisão: 161126 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 130319 [St] Status: MEDLINE

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[PMID]: 23092279 [Au] Autor: Massari S; Sabatini S; Tabarrini O [Ad] Endereço: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy. [Ti] Título: Blocking HIV-1 replication by targeting the Tat-hijacked transcriptional machinery. [So] Source: Curr Pharm Des;19(10):1860-79, 2013. [Is] ISSN: 1873-4286 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: HIV-1 infection can be effectively controlled by HAART, which improves the quality of lives of infected individuals, but fails to completely eradicate the virus, even after decades of treatment. This issue, together with the emergence of multi-drug-resistant viruses, clearly underscores the continuing need to find novel agents able to target vulnerable steps in the viral replication cycle. HIV transcriptional regulation is a crucial step required to re-initiate viral replication from post-integration latency after interruption of therapy and to keep the virus in circulation. In this step, the viral protein Tat plays a central role by dramatically increasing the production of elongated transcripts through its unique interaction with the viral TAR RNA and the cellular cofactor P-TEFb, together with a myriad of other host factors which are recruited to the viral promoter to ensure efficient transcription. The transcriptional machinery, involving an intricate interplay of many viral and cellular components, offers a plethora of potential therapeutic targets that have not yet been exploited by any of the antiretroviral drugs used in therapy. In this review we explore the state-of-the-art of Tat-mediated transcription inhibitors which target the well-consolidated Tat/TAR/PTEFb axis, together with novel therapeutics that interfere with various host-cell factors, including some pioneer inhibitors designed on the basis of recent molecular and structural studies. [Mh] Termos MeSH primário: Genes tat HIV-1/efeitos dos fármacos Transcrição Genética/efeitos dos fármacos Replicação Viral/efeitos dos fármacos [Mh] Termos MeSH secundário: HIV-1/fisiologia Seres Humanos Modelos Moleculares Bibliotecas de Moléculas Pequenas [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW [Nm] Nome de substância: 0 (Small Molecule Libraries) [Em] Mês de entrada: 1308 [Cu] Atualização por classe: 130307 [Lr] Data última revisão: 130307 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 121025 [St] Status: MEDLINE

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