Amit Singh

Bio: Amit Singh is an academic researcher from National Institute of Technology, Patna. The author has contributed to research in topics: Digital watermarking & Watermark. The author has an hindex of 57, co-authored 640 publications receiving 13795 citations. Previous affiliations of Amit Singh include Ithaca College & Center for Infectious Disease Research and Policy.

Phe28B10 Induces Channel-Forming Cytotoxic Amyloid Fibrillation in Human Neuroglobin, the Brain-Specific Hemoglobin

Abstract: Since its discovery, neuroglobin (Ngb), a neuron-specific oxygen binding hemoglobin, distinct from the classical myoglobin and blood hemoglobin, has attracted attention as an endogenous neuroprotectant. Recent reports suggest that Ngb protects neurons from brain stroke, ischemic stress-induced degeneration, and other brain disorders. Proteins with a specific role in neuroprotection are often associated with neurodegeneration, as well, depending on the cellular environment or specific cellular triggers that tilt the balance one way or the other. This investigation explored the potential role of Ngb in amyloid fibril-related neuronal disorder. Ngb was capable of amyloid formation in vitro at neutral pH and ambient temperature, in both apo and holo forms, albeit at a slower rate in the holo form, unlike other hemoglobins that exhibit such behavior exclusively in the apo states. Elevated temperature enhanced the rate of fibril formation significantly. The B-helix, which is known to play a major role in Ngb ligand binding kinetics, was found to be amyloidogenic with the Phe28B10 amino acid side chain as the key inducer of fibrillation. The Ngb amyloid fibril was also significantly cytotoxic to neuroblastoma cell lines, compared to those obtained from reference hemoglobins. The Ngb fibril probably promoted toxicity by inducing channel formation in the cell membrane, as investigated here using synthetic lipid bilayer membranes and the propidium iodide uptake assay. These findings imply that Ngb plays a role in neurodegenerative disorders in vivo, for which there seems to be indirect evidence by association. Ngb thus presents a novel prospect for understanding amyloid-related brain disorders beyond the limited set of proteins currently investigated for such diseases.

The future of drug delivery in cancer treatment

Abstract: Impact of nanotechnology for anticancer therapy has been projected with great promises for the past two decades and has been followed with thousands of research publications and preclinical success stories, but relatively poor clinical outcomes. Nanoparticles have served as excellent delivery vectors for drugs that have poor biological stability and significantly improved their pharmacokinetic profile, but their impact on the course of disease treatment has been relatively insignificant. The failures clearly suggest that the approach toward nanoparticle drug development is flawed and full of assumptions that are unrealistic and should be revisited. This chapter focuses on a critical reevaluation of these overgeneralizations to delineate the truth from misconceptions and identify key physiological, biological, design, and regulatory challenges in the development of nanotherapeutics that should be focused on for better clinical translation.

Taxifolin inhibits GTP binding in wild Apo and mutant (V12G) Apo forms of Ras: Molecular docking and molecular dynamics simulation study

Abstract: Ras proteins, the inner plasma membrane localized small G proteins, are involved in the transduction of external stimuli to its main effector Raf kinase. Point mutation in the H-Ras p21 (G12V) leads to loss of intrinsic GTPase activity so that Ras-GTP complex continuously relay signal which is associated with human cancers. Activation of oncogenic receptor tyrosine kinases also a prominent cause of continuous signal transduction through wild Ras. Taxifolin, a plant originated polyphenol, is a principal active component of several plants such as Larix gmelini. Molecular docking revealed that taxifolin captured GTP binding site in apo Ras (wild/mutant). This interaction might be valuable to target newly synthesized nucleotide unbound Ras. Molecular dynamic simulation revealed that binding of taxifolin was stable at GTP binding site of different Ras forms and may lead to improper functioning of Ras in cancer cells for cancer chemotherapeutics.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Pattern Recognition and Machine Learning

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Shape‐Controlled Synthesis of Metal Nanocrystals: Simple Chemistry Meets Complex Physics?

Abstract: Nanocrystals are fundamental to modern science and technology. Mastery over the shape of a nanocrystal enables control of its properties and enhancement of its usefulness for a given application. Our aim is to present a comprehensive review of current research activities that center on the shape-controlled synthesis of metal nanocrystals. We begin with a brief introduction to nucleation and growth within the context of metal nanocrystal synthesis, followed by a discussion of the possible shapes that a metal nanocrystal might take under different conditions. We then focus on a variety of experimental parameters that have been explored to manipulate the nucleation and growth of metal nanocrystals in solution-phase syntheses in an effort to generate specific shapes. We then elaborate on these approaches by selecting examples in which there is already reasonable understanding for the observed shape control or at least the protocols have proven to be reproducible and controllable. Finally, we highlight a number of applications that have been enabled and/or enhanced by the shape-controlled synthesis of metal nanocrystals. We conclude this article with personal perspectives on the directions toward which future research in this field might take.