The putative role of some conserved water molecules in the structure and function of human transthyretin

Human transthyretin (hTTR) is a multifunctional protein that is involved in several neurodegenerative diseases. Besides the transportation of thyroxin and vitamin A, it is also involved in the proteolysis of apolipoprotein A1 and A beta peptide. Extensive analyses of 32 high-resolution X-ray and neutron diffraction structures of hTTR followed by molecular-dynamics simulation studies using a set of 15 selected structures affirmed the presence of 44 conserved water molecules in its dimeric structure. They are found to play several important roles in the structure and function of the protein. Eight water molecules stabilize the dimeric structure through an extensive hydrogen-bonding network. The absence of some of these water molecules in highly acidic conditions (pH <= 4.0) severely affects the interfacial hydrogen-bond network, which may destabilize the native tetrameric structure, leading to its dissociation. Three pairs of conserved water molecules contribute to maintaining the geometry of the ligand-binding cavities. Some other water molecules control the orientation and dynamics of different structural elements of hTTR. This systematic study of the location, absence, networking and interactions of the conserved water molecules may shed some light on various structural and functional aspects of the protein. The present study may also provide some rational clues about the conserved water-mediated architecture and stability of hTTR.

On the detection of human influence in extreme precipitation over India

Climate change is expected to influence extreme precipitation which in turn might affect risks of pluvial flooding. Recent studies on extreme rainfall over India vary in their definition of extremes, scales of analyses and conclusions about nature of changes in such extremes. Fingerprint-based detection and attribution (D&A) offer a formal way of investigating the presence of anthropogenic signals in hydroclimatic observations. There have been recent efforts to quantify human effects in the components of the hydrologic cycle at large scales, including precipitation extremes. This study conducts a D&A analysis on precipitation extremes over India, considering both univariate and multivariate fingerprints, using a standardized probability-based index (SPI) from annual maximum one-day (RX1D) and five-day accumulated (RX5D) rainfall. The pattern-correlation based fingerprint method is used for the D&A analysis. Transformation of annual extreme values to SPI and subsequent interpolation to coarser grids are carried out to facilitate comparison between observations and model simulations. Our results show that in spite of employing these methods to address scale and physical processes mismatch between observed and model simulated extremes, attributing changes in regional extreme precipitation to anthropogenic climate change is difficult. At very high (95%) confidence, no signals are detected for RX1D, while for the RX5D and multivariate cases only the anthropogenic (ANT) signal is detected, though the fingerprints are in general found to be noisy. The findings indicate that model simulations may underestimate regional climate system responses to increasing human forcings for extremes, and though anthropogenic factors may have a role to play in causing changes in extreme precipitation, their detection is difficult at regional scales and not statistically significant. (C) 2015 Elsevier B.V. All rights reserved.

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions

Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long-term survival of engrafting cells in the body, not only do the cells have to execute liver-specific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and hepatocyte-like cells (day 21) from human embryonic stem cells (hESCs). Day 5, 15 and 21 cells were stimulated with IFN-alpha and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-alpha treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs - LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. (C) 2015 The Authors. Published by Elsevier B.V.

Appraisal of groundwater resource in Holocene soil deposits by resistivity, hydrochemical and granulomerial studies in the Gulf of Mannar Coast from Southern India

This article is aimed to delineate groundwater sources in Holocene deposits area in the Gulf of Mannar Coast from Southern India. For this purpose 2-D electrical resistivity tomography (ERT), hydrochemical and granulomerical studies were carried out and integrated to identify hydrogeological structures and portable groundwater resource in shallow depths which in general appears in the coastal tracts. The 2-D ERT was used to determine the two-dimensional subsurface geological formations by multicore cable with Wenner array. Low resistivity of 1-5 Omega m for saline water appeared due to calcite at the depth of about 5 m below the ground level (bgl). Sea water intrusion was observed around the maximum resistivity as 5 Omega m at the 8 m depth, bgl in the calcite environs, but the calcareous sandstone layer shows around 15-64 Omega m at the 6 m depth, bgl. The hydrochemical variation of TDS, HCO3-, Cl-, Na+, K+, Ca2+, and Mg2+ concentrations was observed for the saline and sea water intrusion in the groundwater system. The granulometic analysis shows that the study area was under the sea between 5400 and 3000 year ago. The events of ice melting an unnatural ice-stone rain/hail among 5000-4000 years ago resulted in the inundation of sea over the area and deposits of late Holocene marine transgression formation up to Puthukottai quartzite region for a stretch of around 17 km.

Biochemical and Behavioral Evaluation of Human MAPT Mutations in Transgenic Drosophila melanogaster

Mutations in the human microtubule-associated protein tau (hMAPT) gene including R406W and V337M result in autosomal dominant neurodegenerative disorder. These mutations lead to hyperphosphorylation and aggregation of Tau protein which is a known genetic factor underlying development of Alzheimer's disease (AD). In the present study, transgenic Drosophila models of AD expressing wild-type and mutant forms of hMAPT exhibit a progressive neurodegeneration which was manifested in the form of early death and impairment of cognitive ability. Moreover, they were also found to have significantly decreased activity of neurotransmitter enzymes accompanied by decreased cellular endogenous antioxidant profile. The extent of neurodegeneration, memory impairment, and biochemical profiles was different in the tau transgenic strains which indicate multiple molecular and cellular responses underlie each particular form of hMAPT.