Genetic affinities of the central Indian tribal populations

Background

The central Indian state Madhya Pradesh is often called as ‘heart of India’ and has always been an important region functioning as a trinexus belt for three major language families (Indo-European, Dravidian and Austroasiatic). There are less detailed genetic studies on the populations inhabited in this region. Therefore, this study is an attempt for extensive characterization of genetic ancestries of three tribal populations, namely; Bharia, Bhil and Sahariya, inhabiting this region using haploid and diploid DNA markers.

Methodology/Principal Findings

Mitochondrial DNA analysis showed high diversity, including some of the older sublineages of M haplogroup and prominent R lineages in all the three tribes. Y-chromosomal biallelic markers revealed high frequency of Austroasiatic-specific M95-O2a haplogroup in Bharia and Sahariya, M82-H1a in Bhil and M17-R1a in Bhil and Sahariya. The results obtained by haploid as well as diploid genetic markers revealed strong genetic affinity of Bharia (a Dravidian speaking tribe) with the Austroasiatic (Munda) group. The gene flow from Austroasiatic group is further confirmed by their Y-STRs haplotype sharing analysis, where we determined their founder haplotype from the North Munda speaking tribe, while, autosomal analysis was largely in concordant with the haploid DNA results.

Conclusions/Significance

Bhil exhibited largely Indo-European specific ancestry, while Sahariya and Bharia showed admixed genetic package of Indo-European and Austroasiatic populations. Hence, in a landscape like India, linguistic label doesn''t unequivocally follow the genetic footprints.     

Effect of novel arecoline thiazolidinones as muscarinic receptor 1 agonist in Alzheimer's dementia models

The discovery of cholinergic deficit in Alzheimer's disease (AD) patient's brain has triggered research efforts, using cholinomimetic approaches for their efficacy in AD therapy. Various therapies may be of potential clinical use in AD. Among these are cholinergic agents, which include muscarinic agonists, acetylcholinesterase inhibitors, and acetylcholine releasing agents. One of the muscarinic agonists tested in AD is arecoline and its bioisosters, which are widely explored as muscarinic receptor 1 agonist (M1 receptor agonist) in AD research. In this regard, five-membered heterocyclic ring system attached arecoline basic nucleus (N-methyl tetrahydropyridines) at third position has been extensively researched on. The present research involved synthesis of arecoline thiazolidinones 5(a-j) by using dipolar addition of 3-aminopyridine and alkyl/aryl carboxaldehydes in presence of gamma ferrite as catalyst. The resulting products were methylated and reduced to get desired products. Subsequently the synthesized arecoline thiazolidinones were subjected to in vitro muscarinic receptor binding studies using male Wistar rat brain (cerebral cortex) membrane homogenate and extended this in vitro study to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Four derivatives (5a-5c and 5e) showed considerable M1 receptor binding affinity (in vitro) and elicited beneficial effects in vivo memory and learning models (Rodent memory evaluation, plus and Y maze studies).     

Muscarinic receptor 1 agonist activity of novel N-arylthioureas substituted 3-morpholino arecoline derivatives in Alzheimer's presenile dementia models

As part of our continuing effort aimed at the development of selective, efficacious and centrally active M1 muscarinic agonists for the treatment of Alzheimer's presenile dementia, a series of N-arylthioureas substituted 3-morpholino arecoline derivatives 9(a-j) were synthesized by using N-benzyl amino ethanol coupling with alpha-bromo acetyl pyridine followed by reduction and cyclization to develop a new class of M1 receptor agonists. Subsequently the synthesized compounds were subjected to in vitro radioligand M1 receptor affinity studies, IP3 formation studies and also to in vivo pharmacological evaluation of memory and learning in male Wistar rats. Derivatives with chloro (9f) and methoxy (9c) groups on the para position of the benzene ring attached to the nitrogen of thiourea showed several fold high affinity for the M1 receptor (in vitro) among all the synthesized molecules 9(a-j), and also significantly elevated IP3 levels and as well elicited beneficial effects in vivo in memory and learning models in rats (rodent memory evaluation, plus and Y maze studies).     

Unveiling Chemically Robust Bimetallic Squarate-Based Metal–Organic Frameworks for Electrocatalytic Oxygen Evolution Reaction

Here, this work reports an innovative strategy for the synthesis of chemically robust metal–organic frameworks (MOFs), and applies them as catalysts for the electrocatalytic oxygen evolution reaction (OER). A bimetallic squarate-based MOF (Sq-MOF) with a zbr topology serves as an excellent platform for electrocatalytic OER owing to its open porous structure, high affinity toward water, and presence of catalytically active 1D metal hydroxide strips. By regulating the Ni²⁺ content in a bimetallic squarate MOF system, the electrochemical structural stability toward OER can be improved. The screening of various metal ratios demonstrates that Ni₃Fe₁ and Ni₂Fe₁ Sq- zbr -MOFs show the best performance for electrocatalytic OER in terms of catalytic activity and structural stability. Ni₂Fe₁ Sq- zbr -MOF shows a low overpotential of 230 mV (at 10 mA cm⁻²) and a small Tafel slope of 37.7 mV dec⁻¹, with an excellent long-term electrochemical stability for the OER. Remarkably, these overpotential values of Ni₂Fe₁ Sq- zbr -MOF are comparable with those of the best-performing layered double hydroxide (LDH) systems and outperforms the commercially available noble-metal-based RuO₂ catalyst for OER under identical operational conditions.     

Inhibition of cell growth by cellular differentiation into adipocyte-like cells in dexamethasone sensitive cancer cell lines

The stress responses in human body lead to secretion of cortisol hormone. The present study investigated the cellular responses on cell growth and cellular differentiation into adipocytes by exposure of synthetic stress hormone, dexamethasone (DEX) in various human cancer and normal cells. After prolonged exposure of cells with 1?μg/ml DEX for 2 weeks, population doubling time (PDT) was significantly (P?P?P?β (GRβ) and peroxisome proliferator-activated receptor γ (PPARγ) were significantly (P?P?相似文献   

The Proneural Molecular Signature Is Enriched in Oligodendrogliomas and Predicts Improved Survival among Diffuse Gliomas

The Cancer Genome Atlas Project (TCGA) has produced an extensive collection of ‘-omic’ data on glioblastoma (GBM), resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt), which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium''s expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6), but also among 75 grade II and grade III samples (p = 2.65e-4). This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n = 43, p = 1.25e-4). Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy.     

Strong myotoxic activity of Trimeresurus malabaricus venom: Role of metalloproteases

Host answers to pathogen attacks define the course of pathogenic events and decide about the fate of the host organism. Infection with coxsackievirus B3 (CVB3) can induce severe myocarditis and pancreatitis. The interplay between host factors and virus components is crucial for the fate of the infected host. As we have shown before, expression of the pro-apoptotic host protein Siva is significantly increased after CVB3 infection, and infected cells are removed by programmed cell death. Analysis of Siva expressed in Escherichia coli revealed that this protein binds three zinc ions, suggesting a rather complex three-dimensional structure. By screening a human heart cDNA library we found a new interaction partner of Siva. The peroxisomal membrane protein PMP22 may be involved in the host response against CVB3. Previous investigations showed that Siva interacts with the cytoplasmic C-terminus of CD27, a member of the tumor necrosis factor receptor group, and transmits an apoptotic signal. With the help of directed two-hybrid assays we determined the N-terminal part of Siva as the binding region for CD27.