Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Estado nutricional y sintomas psicopatologicos en jovenes rurales de la provincial de Tucuman

El estado nutricional es la condición que resulta del balance entre la ingesta de nutrientes y las necesidades de un individuo. Ciertas características psicopatológicas, como síntomas depresivos, ansiedad, relaciones interpersonales deficitarias, entre otros, tienen un peso relevante en las alteraciones del estado nutricional, pudiendo contribuir en el sostenimiento de situaciones patológicas. Objetivos: valorar estado nutricional y analizar síntomas psicopatológicos de jóvenes rurales de Tucumán. Métodos: Estudio descriptivo, transversal, con muestreo incidental. Se tomaron mediciones antropométricas individuales respetando normas internacionales, previo consentimiento informado. Éstas se clasificaron de acuerdo a criterios de la Organización Mundial de la Salud. Además se aplicó el inventario de síntomas SCL-90-R de Derogatis (1994) (versión Casullo & Castro Solano, 1999) y una encuesta sociodemográfica. La muestra estuvo conformada por 193 jóvenes escolarizados, entre 11 y 18 años, residentes en las zonas rurales de El Cadillal y Santa Lucía. Resultados: El 62% (n =119) participó de las mediciones antropométricas. Se encontró un 49% de malnutrición por exceso (9% de obesidad y 40% de sobrepeso). Se observó que los adolescentes con sobrepeso y obesidad referían mayor sensitividad interpersonal (definida como sentimientos de timidez y vergüenza, de inferioridad a los demás, hipersensibilidad a las opiniones y actitudes ajenas y, en general, incomodidad e inhibición en las relaciones interpersonales), acompañados con sentimientos de poca motivación y energía vital, como desesperanza. Respecto a las zonas geográficas, no se hallaron diferencias estadísticas a partir de la prueba t, sin embargo se observó que los jóvenes del Cadillal referían mayor sensitividad interpersonal y presencia de comportamientos hostiles comparados con sus pares de Santa Lucía. Conclusiones: si bien no puede establecerse un perfil psicopatológico del joven con sobrepeso y obesidad, los resultados muestran que el factor psicógeno puede incidir en el mantenimiento del exceso ponderal, y a su vez, que la obesidad se considera un factor de riesgo para la salud mental de estos grupos.Fil: Salazar Burgos, Ramiro Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Esc. Universitaria de Enfermeria; ArgentinaFil: Lacunza, Ana Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Psicología; ArgentinaFil: Caballero, Verónica Mercedes. Universidad Nacional de Tucumán. Facultad de Psicología; ArgentinaFil: Sal, Francisco Javier. Universidad del Norte Santo Tomás de Aquino. Facultad de Ciencias de la Salud; ArgentinaFil: Fernandez, N.. Universidad del Norte Santo Tomás de Aquino. Facultad de Ciencias de la Salud; ArgentinaFil: Diaz, Y.. Universidad del Norte Santo Tomás de Aquino. Facultad de Ciencias de la Salud; ArgentinaFil: Filgueira, Josefina Maria. Universidad del Norte Santo Tomás de Aquino. Facultad de Ciencias de la Salud; ArgentinaFil: Alé, M.. Universidad del Norte Santo Tomás de Aquino. Facultad de Ciencias de la Salud; Argentina18º Reunion de Investigación en Ciencias de la SaludSan Miguel de TucumánArgentinaUniversidad Nacional de Tucumán. Facultad de Medicina. Departamento de Investigació

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory

VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l. in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design, construction techniques and data acquisition system of the HAWC observatory. HAWC is an air-shower array currently under construction at the same site of VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water Cherenkov detectors and two different data acquisition systems. It was in operation between October 2011 and May 2012 with an average live time of 30%. Besides the scientific verification purposes, the eight months of data were used to obtain the results presented in this paper: the detector response to the Forbush decrease of March 2012, and the analysis of possible emission, at energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages, 10 figures). Corresponding authors: A.Marinelli and D.Zaboro

Coulomb excitation of the ∣Tz∣=12,A=23|T_z|=12, A=23 mirror pair

Background: Electric-quadrupole ($E2$) strengths relate to the underlying quadrupole deformation of a nucleus and present a challenge for many nuclear theories. Mirror nuclei in the vicinity of the line of $N=Z$ represent a convenient laboratory for testing deficiencies in such models, making use of the isospin-symmetry of the systems. Purpose: Uncertainties associated with literature $E2$ strengths in \textsuperscript{23}Mg are some of the largest in $T_z=\left|\frac{1}{2}\right|$ nuclei in the $sd$-shell. The purpose of the present work is to improve the precision with which these values are known, to enable better comparison with theoretical models. Methods: Coulomb-excitation measurements of $^{23}$Mg and $^{23}$Na were performed at the TRIUMF-ISAC facility using the TIGRESS spectrometer. They were used to determine the $E2$ matrix elements of mixed $E2$/$M1$ transitions. Results: Reduced $E2$ transition strengths, $B(E2)$, were extracted for \textsuperscript{23}Mg and \textsuperscript{23}Na. Their precision was improved by factors of approximately six for both isotopes, while agreeing within uncertainties with previous measurements. Conclusions: A comparison was made with both shell-model and {\it ab initio} valence-space in-medium similarity renormalization group calculations. Valence-space in-medium similarity-renormalization-group calculations were found to underpredict the absolute $E2$ strength - in agreement with previous studies

Modeling complex metabolic reactions, ecological systems, and financial and legal networks with MIANN models based on Markov-Wiener node descriptors

[Abstract] The use of numerical parameters in Complex Network analysis is expanding to new fields of application. At a molecular level, we can use them to describe the molecular structure of chemical entities, protein interactions, or metabolic networks. However, the applications are not restricted to the world of molecules and can be extended to the study of macroscopic nonliving systems, organisms, or even legal or social networks. On the other hand, the development of the field of Artificial Intelligence has led to the formulation of computational algorithms whose design is based on the structure and functioning of networks of biological neurons. These algorithms, called Artificial Neural Networks (ANNs), can be useful for the study of complex networks, since the numerical parameters that encode information of the network (for example centralities/node descriptors) can be used as inputs for the ANNs. The Wiener index (W) is a graph invariant widely used in chemoinformatics to quantify the molecular structure of drugs and to study complex networks. In this work, we explore for the first time the possibility of using Markov chains to calculate analogues of node distance numbers/W to describe complex networks from the point of view of their nodes. These parameters are called Markov-Wiener node descriptors of order kth (Wk). Please, note that these descriptors are not related to Markov-Wiener stochastic processes. Here, we calculated the Wk(i) values for a very high number of nodes (>100,000) in more than 100 different complex networks using the software MI-NODES. These networks were grouped according to the field of application. Molecular networks include the Metabolic Reaction Networks (MRNs) of 40 different organisms. In addition, we analyzed other biological and legal and social networks. These include the Interaction Web Database Biological Networks (IWDBNs), with 75 food webs or ecological systems and the Spanish Financial Law Network (SFLN). The calculated Wk(i) values were used as inputs for different ANNs in order to discriminate correct node connectivity patterns from incorrect random patterns. The MIANN models obtained present good values of Sensitivity/Specificity (%): MRNs (78/78), IWDBNs (90/88), and SFLN (86/84). These preliminary results are very promising from the point of view of a first exploratory study and suggest that the use of these models could be extended to the high-throughput re-evaluation of connectivity in known complex networks (collation)