222 research outputs found

    Investigating the impact of land-use land-cover change on Indian summer monsoon daily rainfall and temperature during 1951–2005 using a regional climate model

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    Daily moderate rainfall events, which constitute a major portion of seasonal summer monsoon rainfall over central India, have decreased significantly during the period 1951 through 2005. On the other hand, mean and extreme near-surface daily temperature during the monsoon season have increased by a maximum of 1–1.5 °C. Using simulations made with a high-resolution regional climate model (RegCM4) and prescribed land cover of years 1950 and 2005, it is demonstrated that part of the changes in moderate rainfall events and temperature have been caused by land-use/land-cover change (LULCC), which is mostly anthropogenic. Model simulations show that the increase in seasonal mean and extreme temperature over central India coincides with the region of decrease in forest and increase in crop cover. Our results also show that LULCC alone causes warming in the extremes of daily mean and maximum temperatures by a maximum of 1–1.2 °C, which is comparable with the observed increasing trend in the extremes. Decrease in forest cover and simultaneous increase in crops not only reduces the evapotranspiration over land and large-scale convective instability, but also contributes toward decrease in moisture convergence through reduced surface roughness. These factors act together in reducing significantly the moderate rainfall events and the amount of rainfall in that category over central India. Additionally, the model simulations are repeated by removing the warming trend in sea surface temperatures over the Indian Ocean. As a result, enhanced warming at the surface and greater decrease in moderate rainfall events over central India compared to the earlier set of simulations are noticed. Results from these additional experiments corroborate our initial findings and confirm the contribution of LULCC in the decrease in moderate rainfall events and increase in daily mean and extreme temperature over India. Therefore, this study demonstrates the important implications of LULCC over India during the monsoon season. Although, the regional climate model helps in better resolving land–atmosphere feedbacks over the Indian region, the inferences do depend on the fidelity of the model in capturing the features of Indian monsoon realistically. It is proposed that similar studies using a suite of climate models will further enrich our understanding about the role of LULCC in the Indian monsoon climate

    Can Molecular Motors Drive Distance Measurements in Injured Neurons?

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    Injury to nerve axons induces diverse responses in neuronal cell bodies, some of which are influenced by the distance from the site of injury. This suggests that neurons have the capacity to estimate the distance of the injury site from their cell body. Recent work has shown that the molecular motor dynein transports importin-mediated retrograde signaling complexes from axonal lesion sites to cell bodies, raising the question whether dynein-based mechanisms enable axonal distance estimations in injured neurons? We used computer simulations to examine mechanisms that may provide nerve cells with dynein-dependent distance assessment capabilities. A multiple-signals model was postulated based on the time delay between the arrival of two or more signals produced at the site of injury–a rapid signal carried by action potentials or similar mechanisms and slower signals carried by dynein. The time delay between the arrivals of these two types of signals should reflect the distance traversed, and simulations of this model show that it can indeed provide a basis for distance measurements in the context of nerve injuries. The analyses indicate that the suggested mechanism can allow nerve cells to discriminate between distances differing by 10% or more of their total axon length, and suggest that dynein-based retrograde signaling in neurons can be utilized for this purpose over different scales of nerves and organisms. Moreover, such a mechanism might also function in synapse to nucleus signaling in uninjured neurons. This could potentially allow a neuron to dynamically sense the relative lengths of its processes on an ongoing basis, enabling appropriate metabolic output from cell body to processes

    Application of frequency ratio, statistical index, and weights-of-evidence models and their comparison in landslide susceptibility mapping in Central Nepal Himalaya

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    The Mugling–Narayanghat road section falls within the Lesser Himalaya and Siwalik zones of Central Nepal Himalaya and is highly deformed by the presence of numerous faults and folds. Over the years, this road section and its surrounding area have experienced repeated landslide activities. For that reason, landslide susceptibility zonation is essential for roadside slope disaster management and for planning further development activities. The main goal of this study was to investigate the application of the frequency ratio (FR), statistical index (SI), and weights-of-evidence (WoE) approaches for landslide susceptibility mapping of this road section and its surrounding area. For this purpose, the input layers of the landslide conditioning factors were prepared in the first stage. A landslide inventory map was prepared using earlier reports, aerial photographs interpretation, and multiple field surveys. A total of 438 landslide locations were detected. Out these, 295 (67 %) landslides were randomly selected as training data for the modeling using FR, SI, and WoE models and the remaining 143 (33 %) were used for the validation purposes. The landslide conditioning factors considered for the study area are slope gradient, slope aspect, plan curvature, altitude, stream power index, topographic wetness index, lithology, land use, distance from faults, distance from rivers, and distance from highway. The results were validated using area under the curve (AUC) analysis. From the analysis, it is seen that the FR model with a success rate of 76.8 % and predictive accuracy of 75.4 % performs better than WoE (success rate, 75.6 %; predictive accuracy, 74.9 %) and SI (success rate, 75.5 %; predictive accuracy, 74.6 %) models. Overall, all the models showed almost similar results. The resultant susceptibility maps can be useful for general land use planning

    Meta-analysis indicates that common variants at the DISC1 locus are not associated with schizophrenia

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    Several polymorphisms in the Disrupted-in-Schizophrenia-1 (DISC1) gene are reported to be associated with schizophrenia. However, to date, there has been little effort to evaluate the evidence for association systematically. We carried out an imputation-driven meta-analysis, the most comprehensive to date, using data collected from 10 candidate gene studies and three genome-wide association studies containing a total of 11 626 cases and 15 237 controls. We tested 1241 single-nucleotide polymorphisms in total, and estimated that our power to detect an effect from a variant with minor allele frequency >5% was 99% for an odds ratio of 1.5 and 51% for an odds ratio of 1.1. We find no evidence that common variants at the DISC1 locus are associated with schizophrenia

    Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: A hypothesis

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    BACKGROUND: Regular, "moderate", physical exercise is an established non-pharmacological form of treatment for depressive disorders. Brain lateralization has a significant role in the progress of depression. External stimuli such as various stressors or exercise influence the higher functions of the brain (cognition and affect). These effects often do not follow a linear course. Therefore, nonlinear dynamics seem best suited for modeling many of the phenomena, and putative global pathways in the brain, attributable to such external influences. HYPOTHESIS: The general hypothesis presented here considers only the nonlinear aspects of the effects produced by "moderate" exercise and "chronic" stressors, but does not preclude the possibility of linear responses. In reality, both linear and nonlinear mechanisms may be involved in the final outcomes. The well-known neurotransmitters serotonin (5-HT), dopamine (D) and norepinephrine (NE) all have various receptor subtypes. The article hypothesizes that 'Stress' increases the activity/concentration of some particular subtypes of receptors (designated nt(s)) for each of the known (and unknown) neurotransmitters in the right anterior (RA) and left posterior (LP) regions (cortical and subcortical) of the brain, and has the converse effects on a different set of receptor subtypes (designated nt(h)). In contrast, 'Exercise' increases nt(h )activity/concentration and/or reduces nt(s )activity/concentration in the LA and RP areas of the brain. These effects may be initiated by the activation of Brain Derived Neurotrophic Factor (BDNF) (among others) in exercise and its suppression in stress. CONCLUSION: On the basis of this hypothesis, a better understanding of brain neurodynamics might be achieved by considering the oscillations caused by single neurotransmitters acting on their different receptor subtypes, and the temporal pattern of recruitment of these subtypes. Further, appropriately designed and planned experiments will not only corroborate such theoretical models, but also shed more light on the underlying brain dynamics

    Consanguinity and reproductive health among Arabs

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    Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity

    ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

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    Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic in fluences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children,N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic in fluences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors in fluencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic in fluences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptom

    Negative Regulation of Interferon-β Gene Expression during Acute and Persistent Virus Infections

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    The production of type I interferons (IFNs) in response to viral infections is critical for antiviral immunity. However, IFN production is transient, and continued expression can lead to inflammatory or autoimmune diseases. Thus, understanding the mechanisms underlying the negative regulation of IFN expression could lead to the development of novel therapeutic approaches to the treatment of these diseases. We report that the transcription factor IRF3 plays a central role in the negative regulation of interferon-β (IFNβ) expression during both acute and persistent (chronic) virus infections. We show that the degradation of IRF3 during acute infections, rather than the activation of transcriptional repressors, leads to the down regulation of IFNβ expression. We also show that the block to IFNβ expression in mouse embryonic fibroblasts that are persistently infected with Sendai virus (SeV) correlates with the absence of transcriptionally active IRF3. Remarkably, ongoing protein synthesis and viral replication are required to maintain repression of the IFNβ gene in persistently infected cells, as the gene can be activated by the protein synthesis inhibitor cycloheximide, or by the antiviral drug ribavirin. Finally, we show that the SeV V protein inhibits IRF3 activity in persistently infected cells. Thus, in conjunction with the known interference with STAT1 by the SeV C protein, both IFN activation and its signaling pathways are blocked in persistently infected cells. We conclude that the transcription factor IRF3 is targeted for turnover and inactivation through distinct mechanisms from both the host cells and virus, leading to the inhibition of IFNβ gene expression during acute and persistent viral infections. These observations show that IRF3 plays a critical role, not only in the activation of the IFNβ gene, but also in the controlling the duration of its expression. (284 words

    IL-10 transcription is negatively regulated by BAF180, a component of the SWI/SNF chromatin remodeling enzyme

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    <p>Abstract</p> <p>Background</p> <p>SWI/SNF chromatin remodeling enzymes play a critical role in the development of T helper lymphocytes, including Th2 cells, and directly program chromatin structure at Th2 cytokine genes. Different versions of SWI/SNF complexes, including BAF and PBAF, have been described based on unique subunit composition. However, the relative role of BAF and PBAF in Th cell function and cytokine expression has not been reported.</p> <p>Results</p> <p>Here we examine the role of the PBAF SWI/SNF complex in Th cell development and gene expression using mice deficient for a PBAF-specific component, BAF180. We find that T cell development in the thymus and lymphoid periphery is largely normal when the BAF180 gene is deleted late in thymic development. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus.</p> <p>Conclusions</p> <p>These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.</p
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