Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ∼3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like floor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.

Results of an exercise to estimate the costs of interpersonal violence in Jamaica / Resultados de un ejercicio para estimar el costo de la violencia interpersonal en Jamaica

This report describes the application of a draft version of the World Health Organization (WHO)/ United States Centers for Disease Control and Prevention (CDC) Manual for estimating the economic costs of injuries due to interpersonal and self-directed violence to measure costs of injuries from interpersonal violence. METHODS: Fatal incidence data was obtained from the Jamaica Constabulary Force. The incidence of nonfatal violence-related injuries that required hospitalization was estimated using data obtained from patients treated at and/or admitted to three Type A government hospitals in 2006. RESULTS: During 2006, direct medical cost (J$2.1 billion) of injuries due to interpersonal violence accounted for about 12% of Jamaica's total health budget while productivity losses due to violence-related injuries accounted for approximately J$27.5 billion or 160% of Jamaica's total health expenditure and 4% of Jamaica's Gross Domestic Product. CONCLUSIONS: The availability of accurate and reliable data of the highest quality from health-related information systems is critical for providing useful data on the burden of violence and injury to decision-makers. As Ministries of Health take a leading role in violence and injury prevention, data collection and information systems must have a central role. This study describes the results of one approach to examining the economic burden of interpersonal violence in developing countries where the burden of violence is heaviest. The WHO-CDC manual also tested in Thailand and Brazil is a first step towards generating a reference point for resource allocation, priority setting and prevention advocacy.

Este reporte describe la aplicación de una versión preliminar del Manual de Centros de Estados Unidos para el control y prevención de enfermedades (CDC)/Organización Mundial de la Salud (OMS), para estimar el costo económico de las heridas debidas a la violencia interpersonal y la violencia auto-dirigida, con el fin de evaluar los costos de las heridas por violencia interpersonal. MÉTODOS: Datos sobre las incidencias fatales fueron obtenidos de las Oficinas de la Policía de Jamaica. La incidencia de las heridas no fatales relacionadas con la violencia, pero que no obstante requirieron hospitalización, se calculó a partir de pacientes tratados o ingresados en hospitales gubernamentales del tipo A, en el año 2006. RESULTADOS: Durante el 2006, el costo médico directo (2.1 billones JMD) por heridas a causa de violencia interpersonal, representó alrededor del 12% del total del presupuesto para la salud en Jamaica, mientras que las pérdidas de productividad debido a heridas relacionadas con la violencia, representaron aproximadamente 37.5 billones JMD, o 160% del total de gastos de salud y el 4% del producto interno bruto de Jamaica. CONCLUSIONES: Disponer de datos confiables y exactos de la más alta calidad provenientes de los sistemas de información relacionados con la salud, resulta crucial a las hora de suministrar datos útiles sobre la carga de la violencia y las heridas para quienes tienen a su cargo las tomas de decisiones. Como que los Ministros de Salud desempeñan un papel dirigente en la prevención de las heridas y la violencia, la recogida de datos y los sistemas de información tienen que jugar un papel central. Este estudio describe los resultados de un enfoque para examinar la carga económica de la violencia interpersonal en los países en vías de desarrollo, en los cuales la carga de la violencia es más pesada. El manual CDC-OMS también probado en Tailandia y Brasil, es un primer paso hacia la generación de un punto de referencia para asignar recursos, establecer prioridades y defender la prevención.

Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

HTLV-I antibody study in normal individuals and unselected hospital patients in Malaysia.

A serological investigation for human T cell leukemia virus I (HTLV-I) infection was carried out at the University Hospital, Kuala Lumpur. A total of 626 sera from a non-patient population and 1,038 sera from unselected in-patients were screened for HTLV-I antibodies using an enzyme-linked immunosorbent assay (ELISA). 27/1664 (1.6%) were found to be reactive. However, on Western blotting, only 2 sera were confirmed positive, both showing reactions for the major core (p19 and p24) and the envelope (gp46) proteins. Both of the serum samples were from unselected hospital patients. Most of the remaining sera which were reactive on screening showed indeterminate results on Western blotting. These were further tested by radioimmunoprecipitation assay (RIPA) and none of these sera gave a positive reaction. Therefore, only 2/1038 (0.19%) unselected patients could be confirmed to have antibodies to HTLV-I. None of the normal individuals screened showed a positive Western blot result. Our data indicate that HTLV-I infection is present in our population, but at a low prevalence rate.