Ishani Deb

Bio: Ishani Deb is an academic researcher from University of Calcutta. The author has contributed to research in topics: Circadian clock & Circadian rhythm. The author has an hindex of 2, co-authored 5 publications receiving 7 citations.

Engineering of Supramolecular β-Sheet and Nontoxic Amyloid Fibrils from Synthetic Oligopeptides Containing γ-Aminobutyric Acid as the N-Terminal Residue.

Abstract: Here we demonstrate that three synthetic tripeptides containing conformationally flexible γ-aminobutyric acid (γ-Abu) as the N-terminal residue form supramolecular β-sheet and nanofibrillar aggregates upon self-association in aqueous medium. Congo red and thioflavin T binding study establish that these nanofibrillar aggregates are amyloidogenic in nature. The MTT cell survival assay suggests that these amyloid-like nanofibrillar aggregates are nontoxic toward cultured Neuro 2A cells. Interestingly, none of these tripeptides bear sequence identity with any amyloid forming proteins or peptides; however upon self-association, they form supramolecular β-sheet and amyloid-like nanofibrils those are nontoxic in nature. The results highlight the self-assembling nature of the conformationally flexible peptides in aqueous environment and support the hypothesis that amyloid formation is the intrinsic property of the polypeptide chain. Also the cytotoxicity is not predictive from amyloid fibril formation alone. Such nontoxic amyloid fibrils can be exploited in future to design functional biomaterials for various biomedical applications.

Oxygen glucose deprivation impairs circadian clock genes expressions in Neuro 2A neuroblastoma cells unlike C6 glioma

Abstract: Cooperative interactions of neuron and glia, are of utmost importance for proper brain functions. However, neurons are more susceptible to stroke damage compared to glial cells. Since the role of c...

Morpho-functional variation and response pattern of microglia through rodent ontogeny showing infant microglia as stable and adaptive than matured.

Abstract: Microglia, myelo-monocytic lineage cells, that enter in the developing brain at early embryonic stages and integrate in CNS, are involved in almost all neuroinflammatory conditions. We studied how microglia change their responses through the development and maturation of brain in normal physiological conditions using an ex situ model to delineate their age-specific morpho-functional responsiveness. Rapidly isolated microglia from different age-matched rats were characterized with Iba1+ /CD11b/c+ /MHCclassII+ , cultured, studied for cell-cycle/proliferative potency, ROS generation and phagocytosis, viability and morphological analysis induced with GMCSF, MCSF, IL-4, IL-6, IL-10, and IFN-γ. The study showed marked differences in cellular properties, stability, and viability of microglia through ontogeny with specific patterns in their studied functions which were coherent with their in situ morpho-functional attributes. Phagocytic behavior showed a notable shift from ROS independence to dependence toward maturation. Perinatal microglia were found persistent in ex situ environment and neonatal microglia qualified as the most potent and versatile responders for morpho-functional variations under cytokine induced conditions. The study identified that microglia from infants were the most stable, adaptive, and better responders, which can perform as an ex situ model system to study microglial biology.

Circadian rhythms and substance use disorders: A bidirectional relationship.

Abstract: The circadian system organizes circadian rhythms (biological cycles that occur around 24 h) that couple environmental cues (zeitgebers) with internal functions of the organism. The misalignment between circadian rhythms and external cues is known as chronodisruption and contributes to the development of mental, metabolic and other disorders, including cancer, cardiovascular diseases and addictive disorders. Drug addiction represents a global public health concern and affects the health and well-being of individuals, families and communities. In this manuscript, we reviewed evidence indicating a bidirectional relationship between the circadian system and the development of addictive disorders. We provide information on the interaction between the circadian system and drug addiction for each drug or drug class (alcohol, cannabis, hallucinogens, psychostimulants and opioids). We also describe evidence showing that drug use follows a circadian pattern, which changes with the progression of addiction. Furthermore, clock gene expression is also altered during the development of drug addiction in many brain areas related to drug reward, drug seeking and relapse. The regulation of the glutamatergic and dopaminergic neurocircuitry by clock genes is postulated to be the main circadian mechanism underlying the escalation of drug addiction. The bidirectional interaction between the circadian system and drug addiction seems to be mediated by the effects caused by each drug or class of drugs of abuse. These studies provide new insights on the development of successful strategies aimed at restoring/stabilizing circadian rhythms to reduce the risk for addiction development and relapse.

W4-3 Dimerization and Nuclear Entry of mPER Proteins in Mammalian Cells

Abstract: Nuclear entry of circadian oscillatory gene products is a key step for the generation of a 24-hr cycle of the biological clock. We have examined nuclear import of clock proteins of the mammalian period gene family and the effect of serum shock, which induces a synchronous clock in cultured cells. Previously, mCRY1 and mCRY2 have been found to complex with PER proteins leading to nuclear import. Here we report that nuclear translocation of mPER1 and mPER2 (1) involves physical interactions with mPER3, (2) is accelerated by serum treatment, and (3) still occurs in mCry1/mCry2 double-deficient cells lacking a functional biological clock. Moreover, nuclear localization of endogenous mPER1 was observed in cultured mCry1/mCry2 double-deficient cells as well as in the liver and the suprachiasmatic nuclei (SCN) of mCry1/mCry2 double-mutant mice. This indicates that nuclear translocation of at least mPER1 also can occur under physiological conditions (i.e., in the intact mouse) in the absence of any CRY protein. The mPER3 amino acid sequence predicts the presence of a cytoplasmic localization domain (CLD) and a nuclear localization signal (NLS). Deletion analysis suggests that the interplay of the CLD and NLS proposed to regulate nuclear entry of PER in Drosophila is conserved in mammals, but with the novel twist that mPER3 can act as the dimerizing partner.

Supramolecular Antiparallel β-Sheet Formation by Tetrapeptides Based on Amyloid Sequence

Abstract: Self-assembly of short peptides has emerged as an interesting research field for a wide range of applications. Recently, several truncated fragments of long-chain peptides or proteins responsible for different neurodegenerative diseases were studied to understand whether they can mimic the property and function of native peptides or not. It was reported that such a kind of peptide adopts a β-sheet structure in the disease state. It was observed that aromatic amino acid-rich peptide fragments possess a high tendency to adopt a β-sheet conformation. In this article, we are first time reporting the crystal structure of two tetrapeptides: Boc-GAII-OMe (Peptide 1) and Boc-GGVV-OMe (Peptide 2), composed of aliphatic amino acids, and the sequences are similar to the Aβ-peptide fragments Aβ29-32 and Aβ37-40 , respectively. In the solid-state, they are self-assembled in an antiparallel β-sheet fashion. The peptide units are connected by the strong amide hydrogen-bonding (N-H···O) interactions. Apart from that, other noncovalent interactions are also present, which help to stabilize the cross-β-sheet arrangement. Interestingly, in the crystal structure of Peptide 1, noncovalent C···C interaction between the electron-deficient carbonyl carbon, and the electron-rich sp3-carbon atom is observed, which is quite rare in the literature. The calculated torsion angles for these peptides are lying in the β-sheet region of the Ramachandran plot. FT-IR studies also indicate the formation of an antiparallel β-sheet structure in the solid-state. Circular dichroism of the peptides in the aqueous solution also suggests the presence of predominantly β-sheet-like conformation in the aqueous solution. Under cross-polarized light, Congo Red stained both peptides showed green-gold color due to birefringence indicating their amyloidogenic nature. This result indicates that the short peptide composed of aliphatic amino acid is capable of forming a β-sheet structure in the absence of aromatic amino acid and also can mimic the function of the native amyloid peptide.