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1.
Proc Natl Acad Sci U S A ; 107(5): 2247-52, 2010 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-20133868

RESUMO

Infection of Escherichia coli by the T7 phage leads to rapid and selective inhibition of the host RNA polymerase (RNAP)--a multi-subunit enzyme responsible for gene transcription--by a small ( approximately 7 kDa) phage-encoded protein called Gp2. Gp2 is also a potent inhibitor of E. coli RNAP in vitro. Here we describe the first atomic resolution structure of Gp2, which reveals a distinct run of surface-exposed negatively charged amino acid residues on one side of the molecule. Our comprehensive mutagenesis data reveal that two conserved arginine residues located on the opposite side of Gp2 are important for binding to and inhibition of RNAP. Based on a structural model of the Gp2-RNAP complex, we propose that inhibition of transcription by Gp2 involves prevention of RNAP-promoter DNA interactions required for stable DNA strand separation and maintenance of the "transcription bubble" near the transcription start site, an obligatory step in the formation of a transcriptionally competent promoter complex.


Assuntos
Bacteriófago T7/enzimologia , DNA Bacteriano/genética , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Proteínas de Escherichia coli/antagonistas & inibidores , Escherichia coli/enzimologia , Proteínas Repressoras/química , Proteínas Repressoras/fisiologia , Bacteriófago T7/genética , Sítios de Ligação , DNA Bacteriano/metabolismo , Escherichia coli/genética , Genes Bacterianos , Genes Virais , Modelos Moleculares , Complexos Multiproteicos , Mutação , Ressonância Magnética Nuclear Biomolecular , Regiões Promotoras Genéticas , Conformação Proteica , Proteínas Repressoras/genética , Eletricidade Estática , Sítio de Iniciação de Transcrição
2.
J Clin Neurosci ; 56: 95-100, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29980472

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset hereditary stroke syndrome characterized by recurrent stroke and progressive cognitive impairment caused by NOTCH3 mutations. We report here the clinical and molecular findings of three unrelated Hong Kong Chinese families with CADASIL syndrome. Sanger sequencing of genomic DNA revealed a novel heterozygous variant NM_000435.2(NOTCH3):c.[5903_5904insATAA];[5903_5904=] NP_000426.2:p.(Asp1969∗);(Asp1969=) and two previously reported heterozygous mutations NM_000435.2(NOTCH3):c.[328C>T];[328C=] NP_000426.2:p.[(Arg110Cys)];[(Arg110=)] and NM_000435.2(NOTCH3):c.[580T>A];[580T=] NP_000426.2:p.(Cys194Ser);(Cys194=) in the three families respectively. Molecular basis of CADASIL in these three patients were further established. Genetic analysis provides a reliable method for confirming the diagnosis of CADASIL and enables proper genetic counseling and cascade testing.


Assuntos
CADASIL/genética , Mutação , Receptor Notch3/genética , Adulto , Repetição de Anquirina , Feminino , Heterozigoto , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Notch3/química
3.
Ground Water ; 55(4): 577-587, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28297744

RESUMO

To study the spatial and temporal variability of water dynamics and chemical reactions within the coastal groundwater mixing zones (CGMZs), high-resolution periodical and spatial groundwater sampling within CGMZs is needed. However, current samplers and sampling systems may require heavy driving machines to install. There is also possible contamination from the metal materials for current samplers and sampling systems. Here, a permanent multilevel sampling system is designed to sample coastal groundwater within CGMZs. This cost-effective system consists of metal-free materials and can be installed easily. The system is tested in Po Sam Pai and Tingkok, Tolo Harbor and Hong Kong. Major ions, nutrients, stable isotopes and radium and radon isotopes were analyzed and the data provided scientific information to study the fresh-saltwater interface fluctuations, and temporal variations and spatial heterogeneity of geochemical processes occurred within CGMZs. The reliable spatial and temporal data from the sampling system demonstrate that the system functions well and can provide scientific data for coastal aquifer studies.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Rádio (Elemento) , Isótopos , Radônio
4.
Insights Imaging ; 7(3): 399-410, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26960549

RESUMO

UNLABELLED: The increasing prevalence of breast augmentation presents new challenges in breast imaging interpretation. Magnetic resonance imaging (MRI) is recognized as the gold standard for the evaluation of augmented breasts. This article reviews the MRI features of different breast augmentation techniques, their associated complications, and the role of MRI in the assessment of concurrent breast abnormalities. TEACHING POINTS: • MRI has the highest sensitivity and specificity for implant rupture detection. • MRI is able to discriminate the nature of implanted prosthesis or injected materials. • Sensitivity of cancer detection by MRI is not reduced through implants.

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