मैंग्रोव पर्यावरण प्रणाली : भारत में एक निराशाजनक संसाधन

मैंग्रोव पर्यावरण प्रणाली : भारत में एक निराशाजनक संसाध

A Molecular Dynamics Study on RAGE-Aβ42 Interaction and the Influence of G82S RAGE Polymorphism on Aβ Interaction

Interaction of amyloid peptides (Aβ) with receptor for advanced glycation end products (RAGE) elicits an inflammatory response and augments Alzheimer's disease (AD) pathology. The present study was aimed to analyse the interactions of different forms of Aβ42 peptide with ligand binding domain of normal and G82S RAGE and their possible consequences in AD pathology. The structures of RAGE ectodomain (3CJJ), monomeric forms of Aβ42 - 1IYT (apolar) and 1Z0Q (polar) and fibrillar (2BEG) were obtained from PDB. The structure of G82 and S82 RAGE was generated using SWISS MODEL. SIFT and PolyPhen analysis was performed to predict the phenotypic and functional effect of the amino acid substitution. The G82 and S82 variant structures were simulated in GROMACS and the 10 lowest energy structures were docked with different forms of Aβ42 using CLUSPRO in antibody mode. The lowest energy docked structure was further simulated for 5 ns. The structures corresponding to 0-5 ns were taken and the amino acid interactions were generated using PDBSUM. SIFT analysis indicated that G82S SNP had a tolerating effect on the structure of protein but polyphen predicted a probable damaging effect. Highest binding score was obtained with 2BEG docked with both G82 RAGE (-375.84 ± 7.425 Kcal/mol) and G82S variant (-391.09 ± 13.391 Kcal/mol) indicating that the fibrillar form showed better interaction. Compared to G82 RAGE, the S82 variant showed better interaction to all three forms of Aβ42. The results of study indicate that RAGE interacted better with fibrillar form of Aβ42 peptide and G82S mutation enhanced the binding affinity of RAGE towards amyloid peptides leading to enhanced inflammatory response

Spondyloarthropathies That Mimic Ankylosing Spondylitis: A Narrative Review

Ankylosing spondylitis is the most common type of seronegative inflammatory spondyloarthropathy often presenting with low back or neck pain, stiffness, kyphosis and fractures that are initially missed on presentation; however, there are other spondyloarthropathies that may present similarly making it a challenge to establish the correct diagnosis. Here, we will highlight the similarities and unique features of the epidemiology, pathophysiology, presentation, radiographic findings, and management of seronegative inflammatory and metabolic spondyloarthropathies as they affect the axial skeleton and mimic ankylosing spondylitis. Seronegative inflammatory spondyloarthropathies such as psoriatic arthritis, reactive arthritis, noninflammatory spondyloarthropathies such as diffuse idiopathic skeletal hyperostosis, and ochronotic arthritis resulting from alkaptonuria can affect the axial skeleton and present with symptoms similar those of ankylosing spondylitis. These similarities can create a challenge for providers as they attempt to identify a patient’s condition. However, there are characteristic radiographic findings and laboratory tests that may help in the differential diagnosis. Axial presentations of seronegative inflammatory, non-inflammatory, and metabolic spondyloarthropathies occur more often than previously thought. Identification of their associated symptoms and radiographic findings are imperative to effectively diagnose and properly manage patients with these diseases

Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research.

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD

Genetic architecture of Parkinson's disease in the Indian population: harnessing genetic diversity to address critical gaps in Parkinson's disease research

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our “hub-spoke” model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD