Novel pppGpp binding site at the C-terminal region of the Rel enzyme from Mycobacterium smegmatis

Mycobacterium tuberculosis elicits the stringent response under unfavorable growth conditions, such as those encountered by the pathogen inside the host. The hallmark of this response is production of guanosine tetra-and pentaphosphates, collectively termed (p)ppGpp, which have pleiotropic effects on the bacterial physiology. As the stringent response is connected to survival under stress, it is now being targeted for developing inhibitors against bacterial persistence. The Rel enzyme in mycobacteria has two catalytic domains at its N-terminus that are involved in the synthesis and hydrolysis of (p)ppGpp, respectively. However, the function of the C-terminal region of the protein remained unknown. Here, we have identified a binding site for pppGpp in the C-terminal region of Rel. The binding affinity of pppGpp was quantified by isothermal titration calorimetry. The binding site was determined by crosslinking using the nucleotide analog azido-pppGpp, and examining the crosslink product by mass spectrometry. Additionally, mutations in the Rel protein were created to confirm the site of pppGpp binding by isothermal titration calorimetry. These mutants showed increased pppGpp synthesis and reduced hydrolytic activity. We believe that binding of pppGpp to Rel provides a feedback mechanism that allows the protein to detect and adjust the (p)ppGpp level in the cell. Our work suggests that such sites should also be considered while designing inhibitors to target the stringent response.

HuR Displaces Polypyrimidine Tract Binding Protein To Facilitate La Binding to the 3 ` Untranslated Region and Enhances Hepatitis C Virus Replication

HuR is a ubiquitous, RNA binding protein that influences the stability and translation of several cellular mRNAs. Here, we report a novel role for HuR, as a regulator of proteins assembling at the 3' untranslated region (UTR) of viral RNA in the context of hepatitis C virus (HCV) infection. HuR relocalizes from the nucleus to the cytoplasm upon HCV infection, interacts with the viral polymerase (NS5B), and gets redistributed into compartments of viral RNA synthesis. Depletion in HuR levels leads to a significant reduction in viral RNA synthesis. We further demonstrate that the interaction of HuR with the 3' UTR of the viral RNA affects the interaction of two host proteins, La and polypyrimidine tract binding protein (PTB), at this site. HuR interacts with La and facilitates La binding to the 3' UTR, enhancing La-mediated circularization of the HCV genome and thus viral replication. In addition, it competes with PTB for association with the 3' UTR, which might stimulate viral replication. Results suggest that HuR influences the formation of a cellular/viral ribonucleoprotein complex, which is important for efficient initiation of viral RNA replication. Our study unravels a novel strategy of regulation of HCV replication through an interplay of host and viral proteins, orchestrated by HuR. IMPORTANCE Hepatitis C virus (HCV) is highly dependent on various host factors for efficient replication of the viral RNA. Here, we have shown how a host factor (HuR) migrates from the nucleus to the cytoplasm and gets recruited in the protein complex assembling at the 3' untranslated region (UTR) of HCV RNA. At the 3' UTR, it facilitates circularization of the viral genome through interaction with another host factor, La, which is critical for replication. Also, it competes with the host protein PTB, which is a negative regulator of viral replication. Results demonstrate a unique strategy of regulation of HCV replication by a host protein through alteration of its subcellular localization and interacting partners. The study has advanced our knowledge of the molecular mechanism of HCV replication and unraveled the complex interplay between the host factors and viral RNA that could be targeted for therapeutic interventions.

Probabilistic Models for Forecasting Earthquakes in the Northeast Region of India

Northeast India and its adjoining areas are characterized by very high seismic activity. According to the Indian seismic code, the region falls under seismic zone V, which represents the highest seismic-hazard level in the country. This region has experienced a number of great earthquakes, such as the Assam (1950) and Shillong (1897) earthquakes, that caused huge devastation in the entire northeast and adjacent areas by flooding, landslides, liquefaction, and damage to roads and buildings. In this study, an attempt has been made to find the probability of occurrence of a major earthquake (M-w > 6) in this region using an updated earthquake catalog collected from different sources. Thereafter, dividing the catalog into six different seismic regions based on different tectonic features and seismogenic factors, the probability of occurrences was estimated using three models: the lognormal, Weibull, and gamma distributions. We calculated the logarithmic probability of the likelihood function (ln L) for all six regions and the entire northeast for all three stochastic models. A higher value of ln L suggests a better model, and a lower value shows a worse model. The results show different model suits for different seismic zones, but the majority follows lognormal, which is better for forecasting magnitude size. According to the results, Weibull shows the highest conditional probabilities among the three models for small as well as large elapsed time T and time intervals t, whereas the lognormal model shows the lowest and the gamma model shows intermediate probabilities. Only for elapsed time T = 0, the lognormal model shows the highest conditional probabilities among the three models at a smaller time interval (t = 3-15 yrs). The opposite result is observed at larger time intervals (t = 15-25 yrs), which show the highest probabilities for the Weibull model. However, based on this study, the IndoBurma Range and Eastern Himalaya show a high probability of occurrence in the 5 yr period 2012-2017 with >90% probability.

PLUTO plus : Near-Complete Modeling of Affine Transformations for Parallelism and Locality

Affine transformations have proven to be very powerful for loop restructuring due to their ability to model a very wide range of transformations. A single multi-dimensional affine function can represent a long and complex sequence of simpler transformations. Existing affine transformation frameworks like the Pluto algorithm, that include a cost function for modern multicore architectures where coarse-grained parallelism and locality are crucial, consider only a sub-space of transformations to avoid a combinatorial explosion in finding the transformations. The ensuing practical tradeoffs lead to the exclusion of certain useful transformations, in particular, transformation compositions involving loop reversals and loop skewing by negative factors. In this paper, we propose an approach to address this limitation by modeling a much larger space of affine transformations in conjunction with the Pluto algorithm's cost function. We perform an experimental evaluation of both, the effect on compilation time, and performance of generated codes. The evaluation shows that our new framework, Pluto+, provides no degradation in performance in any of the Polybench benchmarks. For Lattice Boltzmann Method (LBM) codes with periodic boundary conditions, it provides a mean speedup of 1.33x over Pluto. We also show that Pluto+ does not increase compile times significantly. Experimental results on Polybench show that Pluto+ increases overall polyhedral source-to-source optimization time only by 15%. In cases where it improves execution time significantly, it increased polyhedral optimization time only by 2.04x.

Investigations of aerosol black carbon from a semi-urban site in the Indo-Gangetic Plain region

Long-term (2009-2012) data from ground-based measurements of aerosol black carbon (BC) from a semi-urban site, Pantnagar (29.0 degrees N, 79.5 degrees E, 231 m amsl), in the Indo-Gangetic Plain (IGP) near the Himalayan foothills are analyzed to study the regional characterization. Large variations are seen in BC at both diurnal and seasonal scales, associated with the mesoscale and synoptic meteorological processes, and local/regional anthropogenic activities. BC diurnal variations show two peaks (morning and evening) arising from the combined effects of the atmospheric boundary layer (ABL) dynamics and local emissions. The diurnal amplitudes as well as the rates of diurnal evolution are the highest in winter season, followed by autumn, and the lowest in summer-monsoon. BC exhibits nearly an inverse relation with mixing layer depth in all seasons; being strongest in winter (R-2 = 0.89) and weakest (R-2 = 0.33) in monsoon (July-August). Unlike BC, co-located aerosol optical depths (AOD) and aerosol absorption are highest in spring over IGP, probably due to the presence of higher abundances of aerosols (including dust) above the ABL (in the free troposphere). AOD (500 nm) showed annual peak (>0.6) in May-June, dominated by coarse mode, while fine mode aerosols dominated in late autumn and early winter. Aerosols profiles from CALIPSO show highest values close to the surface in winter/autumn, similar to the feature seen in surface BC, whereas at altitudes > 2 km, the extinction is maximum in spring/summer. WRF-Chem model is used to simulate BC temporal variations and then compared with observed BC. The model captures most of the important features of the diurnal and seasonal variations but significantly underestimated the observed BC levels, suggesting improvements in diurnal and seasonal varying BC emissions apart from the boundary layer processes. (C) 2015 Elsevier Ltd. All rights reserved.

Inter-comparison and performance evaluation of chemistry transport models over Indian region

Aerosol loading over the South Asian region has the potential to affect the monsoon rainfall, Himalayan glaciers and regional air-quality, with implications for the billions in this region. While field campaigns and network observations provide primary data, they tend to be location/season specific. Numerical models are useful to regionalize such location-specific data. Studies have shown that numerical models underestimate the aerosol scenario over the Indian region, mainly due to shortcomings related to meteorology and the emission inventories used. In this context, we have evaluated the performance of two such chemistry-transport models: WRF-Chem and SPRINTARS over an India-centric domain. The models differ in many aspects including physical domain, horizontal resolution, meteorological forcing and so on etc. Despite these differences, both the models simulated similar spatial patterns of Black Carbon (BC) mass concentration, (with a spatial correlation of 0.9 with each other), and a reasonable estimates of its concentration, though both of them under-estimated vis-a-vis the observations. While the emissions are lower (higher) in SPRINTARS (WRF-Chem), overestimation of wind parameters in WRF-Chem caused the concentration to be similar in both models. Additionally, we quantified the under-estimations of anthropogenic BC emissions in the inventories used these two models and three other widely used emission inventories. Our analysis indicates that all these emission inventories underestimate the emissions of BC over India by a factor that ranges from 1.5 to 2.9. We have also studied the model simulations of aerosol optical depth over the Indian region. The models differ significantly in simulations of AOD, with WRF-Chem having a better agreement with satellite observations of AOD as far as the spatial pattern is concerned. It is important to note that in addition to BC, dust can also contribute significantly to AOD. The models differ in simulations of the spatial pattern of mineral dust over the Indian region. We find that both meteorological forcing and emission formulation contribute to these differences. Since AOD is column integrated parameter, description of vertical profiles in both models, especially since elevated aerosol layers are often observed over Indian region, could be also a contributing factor. Additionally, differences in the prescription of the optical properties of BC between the models appear to affect the AOD simulations. We also compared simulation of sea-salt concentration in the two models and found that WRF-Chem underestimated its concentration vis-a-vis SPRINTARS. The differences in near-surface oceanic wind speeds appear to be the main source of this difference. In-spite of these differences, we note that there are similarities in their simulation of spatial patterns of various aerosol species (with each other and with observations) and hence models could be valuable tools for aerosol-related studies over the Indian region. Better estimation of emission inventories could improve aerosol-related simulations. (C) 2015 Elsevier Ltd. All rights reserved.

Region-of-interest diffuse optical tomography system

Diffuse optical tomography (DOT) using near-infrared light is a promising tool for non-invasive imaging of deep tissue. This technique is capable of quantitative reconstruction of absorption (mu(a)) and scattering coefficient (mu(s)) inhomogeneities in the tissue. The rationale for reconstructing the optical property map is that the absorption coefficient variation provides diagnostic information about metabolic and disease states of the tissue. The aim of DOT is to reconstruct the internal tissue cross section with good spatial resolution and contrast from noisy measurements non-invasively. We develop a region-of-interest scanning system based on DOT principles. Modulated light is injected into the phantom/tissue through one of the four light emitting diode sources. The light traversing through the tissue gets partially absorbed and scattered multiple times. The intensity and phase of the exiting light are measured using a set of photodetectors. The light transport through a tissue is diffusive in nature and is modeled using radiative transfer equation. However, a simplified model based on diffusion equation (DE) can be used if the system satisfies following conditions: (a) the optical parameter of the inhomogeneity is close to the optical property of the background, and (b) mu(s) of the medium is much greater than mu(a) (mu(s) >> mu(a)). The light transport through a highly scattering tissue satisfies both of these conditions. A discrete version of DE based on finite element method is used for solving the inverse problem. The depth of probing light inside the tissue depends on the wavelength of light, absorption, and scattering coefficients of the medium and the separation between the source and detector locations. Extensive simulation studies have been carried out and the results are validated using two sets of experimental measurements. The utility of the system can be further improved by using multiple wavelength light sources. In such a scheme, the spectroscopic variation of absorption coefficient in the tissue can be used to arrive at the oxygenation changes in the tissue. (C) 2016 AIP Publishing LLC.

Anthropogenic aerosol fraction over the Indian region: model simulations versus multi-satellite data analysis

Anthropogenic aerosols play a crucial role in our environment, climate, and health. Assessment of spatial and temporal variation in anthropogenic aerosols is essential to determine their impact. Aerosols are of natural and anthropogenic origin and together constitute a composite aerosol system. Information about either component needs elimination of the other from the composite aerosol system. In the present work we estimated the anthropogenic aerosol fraction (AF) over the Indian region following two different approaches and inter-compared the estimates. We espouse multi-satellite data analysis and model simulations (using the CHIMERE Chemical transport model) to derive natural aerosol distribution, which was subsequently used to estimate AF over the Indian subcontinent. These two approaches are significantly different from each other. Natural aerosol satellite-derived information was extracted in terms of optical depth while model simulations yielded mass concentration. Anthropogenic aerosol fraction distribution was studied over two periods in 2008: premonsoon (March-May) and winter (November-February) in regard to the known distinct seasonality in aerosol loading and type over the Indian region. Although both techniques have derived the same property, considerable differences were noted in temporal and spatial distribution. Satellite retrieval of AF showed maximum values during the pre-monsoon and summer months while lowest values were observed in winter. On the other hand, model simulations showed the highest concentration of AF in winter and the lowest during pre-monsoon and summer months. Both techniques provided an annual average AF of comparable magnitude (similar to 0.43 +/- 0.06 from the satellite and similar to 0.48 +/- 0.19 from the model). For winter months the model-estimated AF was similar to 0.62 +/- 0.09, significantly higher than that (0.39 +/- 0.05) estimated from the satellite, while during pre-monsoon months satellite-estimated AF was similar to 0.46 +/- 0.06 and the model simulation estimation similar to 0.53 +/- 0.14. Preliminary results from this work indicate that model-simulated results are nearer to the actual variation as compared to satellite estimation in view of general seasonal variation in aerosol concentrations.

Load-Unload Response Ratio and Accelerating Moment/Energy Release Critical Region Scaling and Earthquake Prediction

The main idea of the Load-Unload Response Ratio (LURR) is that when a system is stable, its response to loading corresponds to its response to unloading, whereas when the system is approaching an unstable state, the response to loading and unloading becomes quite different. High LURR values and observations of Accelerating Moment/Energy Release (AMR/AER) prior to large earthquakes have led different research groups to suggest intermediate-term earthquake prediction is possible and imply that the LURR and AMR/AER observations may have a similar physical origin. To study this possibility, we conducted a retrospective examination of several Australian and Chinese earthquakes with magnitudes ranging from 5.0 to 7.9, including Australia's deadly Newcastle earthquake and the devastating Tangshan earthquake. Both LURR values and best-fit power-law time-to-failure functions were computed using data within a range of distances from the epicenter. Like the best-fit power-law fits in AMR/AER, the LURR value was optimal using data within a certain epicentral distance implying a critical region for LURR. Furthermore, LURR critical region size scales with mainshock magnitude and is similar to the AMR/AER critical region size. These results suggest a common physical origin for both the AMR/AER and LURR observations. Further research may provide clues that yield an understanding of this mechanism and help lead to a solid foundation for intermediate-term earthquake prediction.

Diagnostico de hemoparasitos en equinos en la region del Pacifico de Nicaragua utilizando frotis sanguineo

Con el objetivo de conocer la presencia de agentes Etiológicos causantes de homoparásitosis en equinos se realizó un estudio en la faja del Pacifico de Nicaragua durante los meses de Abril a Noviembre del 2006, en los Departamentos de Carazo, Chinandega, Granada, León, Managua, Masaya y Rivas. Esta zona geográfica del país presenta una temperatura media anual en el rango de 30ºC a 32ºC y una humedad relativa de 76% ± 78 5%; precipitación pluvial media anual en el rango de 1483.9 a 1970.0 mm; la altitud osciló entre 82.97 msnm a 580.13 msnm. Se realizo un muestreo de 150 equinos mayores de dos años, correspondiente al 1.30 % de la población muestradas, en los cuales se tomo 3cc de sangre de la vena yugular, mediante una punción, a las muestras de sangre se les realizo dos frotis sanguíneos, y se obtuvo el hematocrito de la misma , tiñéndose los frotis sanguíneos por el método de Giemsa, posteriormente se observaron los frotis sanguíneos por cada equino muestrado, se utilizo microscopia óptica de inmersión para identificar lo hemoparásitos haciendo uso de los parámetros morfológicos de sus clasificación taxonómica. Se encontraron 58 equinos positivos de Babesia ssp correspondiente al 38.66 % de los 150 equinos muestrados y 92 casos de equinos negativos de Babesia ssp correspondiente al 61.33 % de los 150 equinos muestrados. Además se encontró prevalencia de Babesia de 5.92% en toda la faja del pacifico, encontrando para cada uno de los Departamentos muestrados son: a Managua con un 7.14 %, Masaya 6.43%, Granada 5.71%, Rivas 7.14%, Carazo 3,57%, León 3,57%, Chinandega 7,86% de Babesia ssp.

Caracterizacion del comportamiento de la estomatitis vesicular en animales domesticos de pezuña hendida en la sexta region (Jinotega y Matagalpa) en el periodo 2008

El presente trabajo se realizó con el fin de contribuir al conocimiento dando a conocer la Caracterización del comportamiento de la estomatitis Vesicular en animales domésticos de pezuña hendida en la región VI (Jinotega y Matagalpa) en el periodo 2008, debido a su gran poder de difusión considerando que en Nicaragua no existe un programa de erradicación o control de la estomatitis vesicular, aunque los humanos también pueden contraer estomatitis vesicular. Se hizo necesario realizar un monitoreo de la enfermedad en esta región, determinar el tipo de cepa que es mas prevalente en la especie de pezuña hendida y el lugar anatómico que más afecta , se tomaron muestras en conjunto con técnicos del MAGFOR y fueron enviadas al Laboratorio de Diagnóstico de Enfermedades Vesiculares (LADIVES) ,localizado en Panamá, se llevó a cabo un análisis estadístico descriptivo, para este análisis se utilizó la información que se colectó en los casos atendidos entre el mes de Julio a Diciembre 2008 y la información retrospectiva de Enero a Junio, con apoyo de la base de datos de Enfermedades Vesiculares que lleva la oficina del Convenio Bilateral Antiaftosa (CAB) del MAGFOR Se elaboraron distribuciones de frecuencia, para las variables; diagnóstico, prevalencia, especie animal y región anatómica, lo que nos accedió informarnos sobre los valores concretos que adoptaron las variables a analizar y sobre el número(o porcentaje) de veces que se repite cada uno de esos valores y nos permitió construir los diagramas con los resultados, concluyendo que de un total de 132 muestras enviadas al laboratorio 82 resultaron positivas a Estomatitis Vesicular, 44 de ellas resultaron al serotipo New Jersey en la zona de Matagalpa y 33 en Jinotega, 5 resultaron positivas al serotipo Indian a en Matagalpa y en la región de Jinotega no se presentó ninguna positiva a este serotipo, la especie más afectada fue el bovino, de las 132 muestras enviadas 129 fueron tomadas en esta especie, siendo las pezuñas el lugar anatómico de mayor predilección para el virus, del total de muestras 91 se tomaran esta región, manifestándose con mayor frecuencia en épocas de lluvia sobre todo en los meses de mayo a octubre.

Fluctuacion poblacional de la broca del fruto del cafeto hypothenemus hampei Ferr. (Coleoptera: Scolytidae) en tres localidades de la VI region, Nicaragua

Durante el período de los meses de junio 1989 a febrero 1990, se estudió la fluctuación poblacional de la broca del fruto del cafeto Hypothenemus hampei Ferr. en alturas de 950,1000 y 11SO m.s.n.m en la Región VI de Nicaragua. La temperatura en las localidades del estudio oscila entre 18 y 212 C. Las mayores precipitaciones se registran de junio a noviembre y la menor de diciembre a febrero. Los niveles máximos de infestación de broca oscilaron entre 0.5 y 1.55% de frutos brocados encontrandose mayores niveles en las menores alturas donde se observa que el incremento de la población ocurre entre los 107 y 246 días después de la floración principal (ddfp). En las alturas superiores a 1000 m.s.n.m las infestaciones comienzan incrementarse en fechas tardías (141 ddfp). Sin embargo, dichos niveles decrecen al momento de la cosecha. El desarrollo de los diferentes estadíos de H. hampei resultó diferentes en las localidades estudiadas. La producción de huevos se inicia más temprano en las zonas de menor altitude (78 ddfp) en comparación con zonas de mayor altitud (141 ddfp). Las poblaciones de huevos, larvas y pupas aumentan posteriormente con al número de adultos, alcanzando los máximos valores durante la maduración del fruto y disminuyendo al momento final de la cosecha. H. hampei se reproduce en frutos semiconsistentes, consistentes y maduros, sin embargo, se puede encontrar adultos de broca en los canales de penetración en los frutos en estado lechoso.

Determinacion de la relacion entre la satisfaccion hidrica y los rendimientos del maiz (Zea mays L.) en la cuarta region

El presente trabajo de investigación se llevó a cabo en la IV región del pais con el fin de obtener una relación entre los diferentes grados de abastecimiento hídrico y los rendimientos del cultivo del maiz, variedad NB-6, para asi poder dar un mejor uso de los recursos hidricos (en nuestro caso las precipitaciones) mediante la determinación de fechas de siembra con el menor riesgo posible de pérdidas económicas. Nos encontramos con la limitante de trabajar con un número no muy grande de muestras debido a perdida de información (registros incompletos) y además de trabajar con solamente un ciclo de producción disminuyendo esto la variabilidad de los datos. Se logró validar efectivamente un modelo de balance hidríco para las condiciones especificas del año en estudio < 1989) y se encontró una relación clara, aunque no rígida, entre el indice de satisfacción hidrica del cultivo y los rendimientos obtenidos en ese año. Sin embargo, se recomienda utilizar modelos mas precisos para este tipo de investigación y repetirlo sobre una serie mayor de años. Por ahora, solo contamos con esta relación obtenida y de utilización reservada.