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1.
Biochem Biophys Res Commun ; 725: 150249, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-38880081

RESUMEN

The HIV-1 envelope glycoprotein (Env) plays crucial role in viral infection by facilitating viral attachment to host cells and inducing fusion of the virus with the host cell membrane. This fusion allows the HIV-1 viral genome to enter the target cell then triggering various stages of the viral life cycle. The native Env directly interacts with the main receptor CD4 and the co-receptor (CCR5 or CXCR4) in human cell membrane then induces membrane fusion. The elucidation of the structure of Env with CD4 and co-receptors in different HIV-1 subtypes is essential for the understanding of the mechanism of virus entry. Here we report the Cryo-EM structure of the CD4-bound HIV-1 heterotrimeric Env from Asia prevalent CRF07_BC CH119 strain. In this structure, the binding of three CD4 molecules with Env induced extensively conformational changes in gp120, resulting in the transformation of the Env from close state to intermediate open state. Additionally, the conformational shift of V1/V2 loops of the heterotrimeric Env allosterically expose the V3 loop and promoting the further interactions with co-receptor CCR5 or CXCR4. These findings not only illustrate the structural complexity and plasticity of HIV-1 Env but also give new insights how the biological trimeric Env initialize the immune recognition and membrane fusion.


Asunto(s)
Antígenos CD4 , Proteína gp120 de Envoltorio del VIH , VIH-1 , VIH-1/metabolismo , Humanos , Antígenos CD4/metabolismo , Antígenos CD4/química , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/genética , Microscopía por Crioelectrón , Productos del Gen env del Virus de la Inmunodeficiencia Humana/metabolismo , Productos del Gen env del Virus de la Inmunodeficiencia Humana/química , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Receptores CCR5/metabolismo , Receptores CCR5/química , Unión Proteica , Modelos Moleculares , Conformación Proteica , Infecciones por VIH/virología , Infecciones por VIH/metabolismo , Multimerización de Proteína , Receptores CXCR4/metabolismo , Receptores CXCR4/química , Asia
2.
Biochem Biophys Res Commun ; 601: 146-152, 2022 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-35247768

RESUMEN

The AAA + ATPase p97 is a well-known hexametric enzyme that is evolutionary conserved in eukaryotes. p97 contains an amino-terminal N domain, two tandem ATPase domains (D1 and D2 domain) and a C-terminal unstructured extensive tail, involved in many cellular processes and plays important biological functions, but the structural basis of p97 for its biological roles still remain unclear. Here we report the Cryo-EM structure of full-length human p97 dodecamer in 3.0 Å resolution, the structure was captured in ADP-bound form but only D1 ATPase sites were well occupied by nucleotide and D2 sites are empty, furthermore, 12 non-ATP-competitive inhibitors of NMS-873 bound in the interface between each p97 monomer. We also found that the C-terminal S765-G779 (765-'SRGFGSFRFPSGNQG'-779) peptide plays critical roles for the D2 ring oligomerization, biochemical and electron microscopy studies confirm that the S765-G779 peptide could induce the D2 ring itself to form the heptamer, this give new insights how p97 protomers assemble to the biological functional multimers.


Asunto(s)
Adenosina Trifosfatasas , Péptidos , Acetanilidas , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Benzotiazoles , Microscopía por Crioelectrón , Humanos , Péptidos/metabolismo , Estructura Terciaria de Proteína , Proteína que Contiene Valosina/metabolismo
3.
Sci Rep ; 10(1): 4700, 2020 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-32170187

RESUMEN

Allergic responses are mainly caused by IgE, which is often located on the cell surface. The current diagnostic method detects both allergen-specific IgE and total IgE levels, but a number of allergic patients have a normal serum IgE level, which is a poor clinical correlate for allergy. Here, we developed a simple method to detect the level of cell-bound IgE by dissociating it from blood cells with lactic acid. Dissociated cell-bound IgE and plasma IgE levels were detected using the same ELISA kit at the same time. We established two clinical cohorts: an allergic patient group and a healthy participant group. In general, cell-bound IgE correlated well with plasma IgE; however, some patients exhibited high cell-bound IgE levels but low plasma IgE levels. We recommended 350 ng/mL peripheral blood total IgE (cell-bound IgE + plasma IgE) as the cut-off value for allergy diagnosis. Using this indicator, 90.32% of our allergic patients were correctly diagnosed. The peripheral blood total IgE level is a promising clinical diagnostic indicator in allergic patients and will provide more guidance for allergy diagnosis and therapeutic evaluation.


Asunto(s)
Biomarcadores , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Hipersensibilidad/sangre , Hipersensibilidad/metabolismo , Inmunoglobulina E/sangre , Masculino , Pronóstico
4.
Water Environ Res ; 79(8): 851-7, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17824531

RESUMEN

This study investigates the products, kinetics, and reactor design of atrazine photolysis under 254-nm ultraviolet-C (UVC) irradiation. With an initial atrazine concentration of 60 microg/L (60 ppbm), only two products remain in detectable levels. Up to 77% of decomposed atrazine becomes hydroxyatrazine, the major product. Both atrazine and hydroxyatrazine photodecompose following the first-order rate equation, but the hydroxyatrazine photodecomposition rate is significantly slower than that of atrazine. For atrazine photodecomposition, the rate constant is proportional to the square of UVC output, but inversely proportional to the reactor volume. For a photochemical reactor design, a series of equations are proposed to calculate the needed UVC output power, water treatment capacity, and atrazine outlet concentration.


Asunto(s)
Atrazina/efectos de la radiación , Herbicidas/efectos de la radiación , Fotólisis , Rayos Ultravioleta , Contaminantes Químicos del Agua/efectos de la radiación , Atrazina/química , Herbicidas/química , Cinética , Proyectos Piloto , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos
5.
Soc Psychiatry Psychiatr Epidemiol ; 42(9): 716-22, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17598056

RESUMEN

OBJECTIVES: There are currently around 120 million rural-urban migrants in China. Elsewhere migration has been associated with increased vulnerability to mental health problems. This study was conducted to explore the mental health status and help seeking behaviours of migrant workers in Hangzhou city, Zhejiang Province, and to compare them with permanent urban and rural dwellers. METHODS: A self-completion questionnaire including items relating to sociodemographics, health and lifestyles and mental health, was completed by 4453 migrant workers and 1957 urban workers in Hangzhou city, and by 1909 rural residents in Western Zhejiang Province. RESULTS: The mean age of the migrants was 27 years, (male 29 years, female 25 years). They worked long hours (28% >12 h per day, 81% 6 or 7 days per week) and their living conditions were very basic. On the SF-36 mental health scale migrants had lower scores (52.4) than rural residents (60.4, P < 0.0001) but scored higher than urban residents (47.2, P = 0.003). The difference between urbanites and migrants disappeared after adjustment for confounders (P = 0.06). Independent predictors of better mental health status among migrants were being unmarried, migrating with a partner, higher salary, good self-reported health and good relationships with co-workers. There were small significant differences in suicide ideation and attempts between the three groups with suicide ideation commonest in migrants and suicide attempts most common in the rural population. Fewer than 1% across all three groups had received any professional help for depression or anxiety. CONCLUSION: Rural-urban migrant workers in this part of China are not especially vulnerable to poor mental health. This may result from a sense of well being associated with upward economic mobility and improved opportunities, and the relatively high social capital in migrant communities.


Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Estado de Salud , Trastornos Mentales/epidemiología , Población Rural/estadística & datos numéricos , Migrantes/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adulto , China/epidemiología , Estudios Transversales , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Factores de Tiempo
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