Institute for Stem Cell Biology and Regenerative Medicine inStem

Bangalore, India

Institute for Stem Cell Biology and Regenerative Medicine inStem

Bangalore, India
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Raj S.B.,University of Iowa | Raj S.B.,Lawson State Community College | Ramaswamy S.,University of Iowa | Ramaswamy S.,Institute for Stem Cell Biology and Regenerative Medicine inSTEM | Plapp B.V.,University of Iowa
Biochemistry | Year: 2014

Yeast (Saccharomyces cerevisiae) alcohol dehydrogenase I (ADH1) is the constitutive enzyme that reduces acetaldehyde to ethanol during the fermentation of glucose. ADH1 is a homotetramer of subunits with 347 amino acid residues. A structure for ADH1 was determined by X-ray crystallography at 2.4 Å resolution. The asymmetric unit contains four different subunits, arranged as similar dimers named AB and CD. The unit cell contains two different tetramers made up of "back-to-back" dimers, AB:AB and CD:CD. The A and C subunits in each dimer are structurally similar, with a closed conformation, bound coenzyme, and the oxygen of 2,2,2-trifluoroethanol ligated to the catalytic zinc in the classical tetrahedral coordination with Cys-43, Cys-153, and His-66. In contrast, the B and D subunits have an open conformation with no bound coenzyme, and the catalytic zinc has an alternative, inverted coordination with Cys-43, Cys-153, His-66, and the carboxylate of Glu-67. The asymmetry in the dimeric subunits of the tetramer provides two structures that appear to be relevant for the catalytic mechanism. The alternative coordination of the zinc may represent an intermediate in the mechanism of displacement of the zinc-bound water with alcohol or aldehyde substrates. Substitution of Glu-67 with Gln-67 decreases the catalytic efficiency by 100-fold. Previous studies of structural modeling, evolutionary relationships, substrate specificity, chemical modification, and site-directed mutagenesis are interpreted more fully with the three-dimensional structure. © 2014 American Chemical Society.

Rumman M.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Rumman M.,Manipal University India | Dhawan J.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Dhawan J.,CSIR - Central Electrochemical Research Institute | And 3 more authors.
Stem Cells | Year: 2015

Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim of this review is to provide an update regarding the biological mechanisms of ASC quiescence and their role in tissue regeneration. © 2015 AlphaMed Press.

Eipper-Mains J.E.,University of Connecticut Health Center | Kiraly D.D.,University of Connecticut Health Center | Palakodeti D.,University of Connecticut Health Center | Palakodeti D.,Institute for Stem Cell Biology and Regenerative Medicine inStem | And 3 more authors.
RNA | Year: 2011

MicroRNAs (miRNAs) are small RNAs that modulate gene expression by binding target mRNAs. The hundreds of miRNAs expressed in the brain are critical for synaptic development and plasticity. Drugs of abuse cause lasting changes in the limbic regions of the brain that process reward, and addiction is viewed as a form of aberrant neuroplasticity. Using next-generation sequencing, we cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes. The miR-8 family, known for its roles in cancer, is highly enriched and cocaine regulated at striatal synapses, where its members may affect expression of cell adhesion molecules. Synaptically enriched cocaine-regulated miRNAs may contribute to long-lasting drug-induced plasticity through fine-tuning regulatory pathways that modulate the actin cytoskeleton, neurotransmitter metabolism, and peptide hormone processing. Published by Cold Spring Harbor Laboratory Press. Copyright © 2011 RNA Society.

Plapp B.V.,University of Iowa | Ramaswamy S.,University of Iowa | Ramaswamy S.,Institute for Stem Cell Biology and Regenerative Medicine InSTEM
Biochemistry | Year: 2012

Structures of horse liver alcohol dehydrogenase complexed with NAD + and unreactive substrate analogues, 2,2,2-trifluoroethanol or 2,3,4,5,6-pentafluorobenzyl alcohol, were determined at 100 K at 1.12 or 1.14 Å resolution, providing estimates of atomic positions with overall errors of ∼0.02 Å, the geometry of ligand binding, descriptions of alternative conformations of amino acid residues and waters, and evidence of a strained nicotinamide ring. The four independent subunits from the two homodimeric structures differ only slightly in the peptide backbone conformation. Alternative conformations for amino acid side chains were identified for 50 of the 748 residues in each complex, and Leu-57 and Leu-116 adopt different conformations to accommodate the different alcohols at the active site. Each fluoroalcohol occupies one position, and the fluorines of the alcohols are well-resolved. These structures closely resemble the expected Michaelis complexes with the pro-R hydrogens of the methylene carbons of the alcohols directed toward the re face of C4N of the nicotinamide rings with a C-C distance of 3.40 Å. The oxygens of the alcohols are ligated to the catalytic zinc at a distance expected for a zinc alkoxide (1.96 Å) and participate in a low-barrier hydrogen bond (2.52 Å) with the hydroxyl group of Ser-48 in a proton relay system. As determined by X-ray refinement with no restraints on bond distances and planarity, the nicotinamide rings in the two complexes are slightly puckered (quasi-boat conformation, with torsion angles of 5.9° for C4N and 4.8° for N1N relative to the plane of the other atoms) and have bond distances that are somewhat different compared to those found for NAD(P)+. It appears that the nicotinamide ring is strained toward the transition state on the path to alcohol oxidation. © 2012 American Chemical Society.

Kusumi A.,Kyoto University | Fujiwara T.K.,Kyoto University | Morone N.,Kyoto University | Yoshida K.J.,Kyoto University | And 6 more authors.
Seminars in Cell and Developmental Biology | Year: 2012

Virtually all biological membranes on earth share the basic structure of a two-dimensional liquid. Such universality and peculiarity are comparable to those of the double helical structure of DNA, strongly suggesting the possibility that the fundamental mechanisms for the various functions of the plasma membrane could essentially be understood by a set of simple organizing principles, developed during the course of evolution. As an initial effort toward the development of such understanding, in this review, we present the concept of the cooperative action of the hierarchical three-tiered meso-scale (2-300. nm) domains in the plasma membrane: (1) actin membrane-skeleton-induced compartments (40-300. nm), (2) raft domains (2-20. nm), and (3) dynamic protein complex domains (3-10. nm). Special attention is paid to the concept of meso-scale domains, where both thermal fluctuations and weak cooperativity play critical roles, and the coupling of the raft domains to the membrane-skeleton-induced compartments as well as dynamic protein complexes. The three-tiered meso-domain architecture of the plasma membrane provides an excellent perspective for understanding the membrane mechanisms of signal transduction. © 2012 .

Lalitha K.,SASTRA University | Muthusamy K.,SASTRA University | Prasad Y.S.,SASTRA University | Vemula P.K.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Nagarajan S.,SASTRA University
Carbohydrate Research | Year: 2015

In the last few years, considerable progress has been made in the synthesis of C-glycosides. Despite its challenging chemistry, due to its versatility, C-glycosides play a pivotal role in developing novel materials, surfactants and bioactive molecules. In this review, we present snapshots of various synthetic methodologies developed for C-glycosides in the recent years and the potential application of C-glycosides derived from β-C-glycosidic ketones © 2014 Elsevier Ltd. All rights reserved..

Rao R.A.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Rao R.A.,SASTRA University | Dhele N.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Cheemadan S.,Center for Stem Cell Research | And 4 more authors.
Scientific Reports | Year: 2015

Factor induced reprogramming of fibroblasts is an orchestrated but inefficient process. At the epigenetic level, it results in drastic chromatin changes to erase the existing somatic "memory" and to establish the pluripotent state. Accordingly, alterations of chromatin regulators including Ezh2 influence iPSC generation. While the role of individual transcription factors in resetting the chromatin landscape during iPSC generation is increasingly evident, their engagement with chromatin modulators remains to be elucidated. In the current study, we demonstrate that histone methyl transferase activity of Ezh2 is required for mesenchymal to epithelial transition (MET) during human iPSC generation. We show that the H3K27me3 activity favors induction of pluripotency by transcriptionally targeting the TGF-β signaling pathway. We also demonstrate that the Ezh2 negatively regulates the expression of pro-EMT miRNA's such as miR-23a locus during MET. Unique association of Ezh2 with c-Myc was required to silence the aforementioned circuitry. Collectively, our findings provide a mechanistic understanding by which Ezh2 restricts the somatic programme during early phase of cellular reprogramming and establish the importance of Ezh2 dependent H3K27me3 activity in transcriptional and miRNA modulation during human iPSC generation.

Anand T.,Madurai Kamaraj University | Sivaraman G.,Madurai Kamaraj University | Sivaraman G.,Institute for Stem Cell Biology and Regenerative Medicine inStem | Iniya M.,Madurai Kamaraj University | And 2 more authors.
Analytica Chimica Acta | Year: 2015

Chemosensors based on aminobenzohydrazide Schiff bases bearing pyrene/anthracene as fluorophores have been designed and synthesized for F- ion recognition. The addition of fluoride ions to the receptors causes a dramatically observable colour change from pale yellow to brown/red. 1H NMR studies confirm that the F- ion facilitates its recognition by forming hydrogen bond with hydrogens of amide and amine groups. Moreover these sensors have also been successfully applied to detection of fluoride ion in commercial tooth paste solution. © 2015 Elsevier B.V..

Krishna S.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Nair A.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Cheedipudi S.,Institute for Stem Cell Biology and Regenerative Medicine InStem | Cheedipudi S.,Max Planck Institute for Heart and Lung Research | And 4 more authors.
Nucleic Acids Research | Year: 2013

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem-loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping-pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration. © 2012 The Author(s). Published by Oxford University Press.

Vemula P.K.,Institute for Stem Cell Biology and Regenerative Medicine inStem | Wiradharma N.,Harvard-MIT Division of Health Sciences and Technology | Ankrum J.A.,Harvard-MIT Division of Health Sciences and Technology | Miranda O.R.,Harvard-MIT Division of Health Sciences and Technology | And 2 more authors.
Current Opinion in Biotechnology | Year: 2013

Prodrug-based self-assembled hydrogels represent a new class of active biomaterials that can be harnessed for medical applications, in particular the design of stimuli responsive drug delivery devices. In this approach, a promoiety is chemically conjugated to a known-drug to generate an amphiphilic prodrug that is capable of forming self-assembled hydrogels. Prodrug-based self-assembled hydrogels are advantageous as they alter the solubility of the drug, enhance drug loading, and eliminate the use of harmful excipients. In addition, self-assembled prodrug hydrogels can be designed to undergo controlled drug release or tailored degradation in response to biological cues. Herein we review the development of prodrug-based self-assembled hydrogels as an emerging class of biomaterials that overcome several common limitations encountered in conventional drug delivery. © 2013 .

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