The International Center for Genetic Engineering and Biotechnology

Delhi, India

The International Center for Genetic Engineering and Biotechnology

Delhi, India
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PubMed | the International Center for Genetic Engineering and Biotechnology, Jamia Millia Islamia University and Indian Institute of Science
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015

Redox signaling plays a crucial role in the pathogenesis of human immunodeficiency virus type-1 (HIV-1). The majority of HIV redox research relies on measuring redox stress using invasive technologies, which are unreliable and do not provide information about the contributions of subcellular compartments. A major technological leap emerges from the development of genetically encoded redox-sensitive green fluorescent proteins (roGFPs), which provide sensitive and compartment-specific insights into redox homeostasis. Here, we exploited a roGFP-based specific bioprobe of glutathione redox potential (E(GSH); Grx1-roGFP2) and measured subcellular changes in E(GSH) during various phases of HIV-1 infection using U1 monocytic cells (latently infected U937 cells with HIV-1). We show that although U937 and U1 cells demonstrate significantly reduced cytosolic and mitochondrial E(GSH) (approximately -310 mV), active viral replication induces substantial oxidative stress (E(GSH) more than -240 mV). Furthermore, exposure to a physiologically relevant oxidant, hydrogen peroxide (H2O2), induces significant deviations in subcellular E(GSH) between U937 and U1, which distinctly modulates susceptibility to apoptosis. Using Grx1-roGFP2, we demonstrate that a marginal increase of about 25 mV in E(GSH) is sufficient to switch HIV-1 from latency to reactivation, raising the possibility of purging HIV-1 by redox modulators without triggering detrimental changes in cellular physiology. Importantly, we show that bioactive lipids synthesized by clinical drug-resistant isolates of Mycobacterium tuberculosis reactivate HIV-1 through modulation of intracellular E(GSH). Finally, the expression analysis of U1 and patient peripheral blood mononuclear cells demonstrated a major recalibration of cellular redox homeostatic pathways during persistence and active replication of HIV.


Malara A.,University of Pavia | Malara A.,IRCCS San Matteo Foundation | Gruppi C.,University of Pavia | Celesti G.,Humanitas Clinical and Research Center | And 7 more authors.
Stem Cells | Year: 2016

Fibronectin (FN) is a major extracellular matrix protein implicated in cell adhesion and differentiation in the bone marrow (BM) environment. Alternative splicing of FN gene results in the generation of protein variants containing an additional EIIIA domain that sustains cell proliferation or differentiation during physiological or pathological tissue remodeling. To date its expression and role in adult hematopoiesis has not been explored. In our research, we demonstrate that during physiological hematopoiesis a small fraction of BM derived FN contains the EIIIA domain and that mice constitutively including (EIIIA+/+) or excluding (EIIIA−/−) the EIIIA exon present comparable levels of hematopoietic stem cells, myeloid and lymphoid progenitors within BM. Moreover, only minor alterations were detected in blood parameters and in hematopoietic frequencies of BM granulocytes/monocytes and B cells. As opposed to other tissues, unique compensatory mechanisms, such as increased FN accumulation and variable expression of the EIIIA receptors, Toll like receptor-4 and alpha9 integrin subunit, characterized the BM of these mice. Our data demonstrate that FN is a fundamental component of the hematopoietic tissue and that the EIIIA exon may play a key role in modulating hematopiesis in conditions of BM stress or diseases. Stem Cells 2016;34:2263–2268. © 2016 AlphaMed Press


PubMed | Humanitas Clinical and Research Center, National Diagnostics, University of Pavia, The International Center for Genetic Engineering and Biotechnology and Apheresis and Cell Therapy Unit
Type: Journal Article | Journal: Stem cells (Dayton, Ohio) | Year: 2016

Fibronectin (FN) is a major extracellular matrix protein implicated in cell adhesion and differentiation in the bone marrow (BM) environment. Alternative splicing of FN gene results in the generation of protein variants containing an additional EIIIA domain that sustains cell proliferation or differentiation during physiological or pathological tissue remodeling. To date its expression and role in adult hematopoiesis has not been explored. In our research, we demonstrate that during physiological hematopoiesis a small fraction of BM derived FN contains the EIIIA domain and that mice constitutively including (EIIIA(+/+) ) or excluding (EIIIA(-/-) ) the EIIIA exon present comparable levels of hematopoietic stem cells, myeloid and lymphoid progenitors within BM. Moreover, only minor alterations were detected in blood parameters and in hematopoietic frequencies of BM granulocytes/monocytes and B cells. As opposed to other tissues, unique compensatory mechanisms, such as increased FN accumulation and variable expression of the EIIIA receptors, Toll like receptor-4 and alpha9 integrin subunit, characterized the BM of these mice. Our data demonstrate that FN is a fundamental component of the hematopoietic tissue and that the EIIIA exon may play a key role in modulating hematopiesis in conditions of BM stress or diseases. Stem Cells 2016;34:2263-2268.


Miorin L.,The International Center for Genetic Engineering and Biotechnology | Albornoz A.,The International Center for Genetic Engineering and Biotechnology | Baba M.M.,The International Center for Genetic Engineering and Biotechnology | D'Agaro P.,University of Trieste | Marcello A.,The International Center for Genetic Engineering and Biotechnology
Virus Research | Year: 2012

Interferons are key mediators of the innate antiviral response of the cell against viral infections. Viruses on the other hand have evolved various strategies to delay innate immunity in order to establish a productive infection. In this work we analyzed the pathway of interferon induction by the tick-borne encephalitis virus. We initially observed a consistent delay of interferon induction following virus replication. RIG-I, but not MDA5, and nuclear translocation of IRF3 were eventually required for interferon activation pointing to a defect in pattern recognition receptor's signaling. However, viral proteins could not directly inhibit the pathway suggesting an indirect mechanism. We found that dsRNA replication intermediates and replicated viral RNA localized to membrane-defined perinuclear compartments that resisted RNAse treatment. Thus, initial escape from innate immunity involved the formation of replication vesicles that may function as a barrier to pattern recognition receptors. © 2011 Elsevier B.V.


Sharma E.,Govind Ballabh Pant University of Agriculture & Technology | Pandey S.,The International Center for Genetic Engineering and Biotechnology | Gaur A.K.,Govind Ballabh Pant University of Agriculture & Technology
Acta Physiologiae Plantarum | Year: 2016

In higher plants, two pathways are implicated in the synthesis of isoprenoids: the mevalonate pathway and methyl-d-erythritol 4-phosphate (MEP) pathway. In MEP pathway, 1-deoxy-d-xylulose-5-phosphate synthase (DXS) enzyme catalyzes the first committed step and it is recognized as a rate-limiting enzyme. In this study, a partial cDNA encoding DXS1 domain isolated from Aconitum balfourii Stapf. was cloned and characterized (AbDXS1). Analysis of DXS domain was performed and we found that AbDXS1 had extensive similarities to other DXS1 proteins. It comprised highly conserved DRAG and PSD domains. A comparative analysis of expression patterns for AbDXS1 using the already existing transcriptome profiles of model plants suggests its role in primary metabolism which needs to be validated further through functional genomics. These data would be helpful for exploring the functions of DXS and its isoforms in MEP pathway of Aconitum balfourii Stapf. © 2016, Franciszek Górski Institute of Plant Physiology, Polish Academy of Sciences, Kraków.


PubMed | the International Center for Genetic Engineering and Biotechnology, University of Udine, University of Buenos Aires and From the Laboratorio Nazionale del Consorzio Interuniversitario per le Biotecnologie
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015

MageB2 belongs to the melanoma antigen gene (MAGE-I) family of tumor-specific antigens. Expression of this gene has been detected in human tumors of different origins. However, little is known about the protein function and how its expression affects tumor cell phenotypes. In this work, we found that human MageB2 protein promotes tumor cell proliferation in a p53-independent fashion, as observed both in cultured cells and growing tumors in mice. Gene expression analysis showed that MageB2 enhances the activity of E2F transcription factors. Mechanistically, the activation of E2Fs is related to the ability of MageB2 to interact with the E2F inhibitor HDAC1. Cellular distribution of MageB2 protein includes the nucleoli. Nevertheless, ribotoxic drugs rapidly promote its nucleolar exit. We show that MageB2 counteracts E2F inhibition by ribosomal proteins independently of Mdm2 expression. Importantly, MageB2 plays a critical role in impairing cell cycle arrest in response to Actinomycin D. The data presented here support a relevant function for human MageB2 in cancer cells both under cycling and stressed conditions, presenting a distinct functional feature with respect to other characterized MAGE-I proteins.


PubMed | the International Center for Genetic Engineering and Biotechnology
Type: | Journal: Biosensors & bioelectronics | Year: 2013

Integrated biochips exploit a multi-disciplinary approach to produce portable point-of-care medical diagnostic systems that uncouple diagnosis from centralized laboratories. These portable devices are cost effective and have several advantages including broader accessibility to health care worldwide. Fluorescence detection of a disease-specific probe excited by an optical source is one of the most diffused methods for quantitative analysis on biochips. Here we designed and characterized a miniaturized biochip based on a novel deep-blue organic light-emitting diode. The molecular design of the diode was optimized to excite a fluorophore-conjugated antibody and tested on a protein microarray configuration with good sensitivity and specificity. These findings will be instrumental for the development of next generation point-of-care biochips.


PubMed | the International Center for Genetic Engineering and Biotechnology and All India Institute of Medical Sciences
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2016

Elucidating the molecular mechanisms of the host-parasite interaction during red cell invasion by Plasmodium is important for developing newer antimalarial therapeutics. Recently, we have characterized a Plasmodium vivax tryptophan-rich antigen PvTRAg38, which is expressed by its merozoites, binds to host erythrocytes, and interferes with parasite growth. Interaction of this parasite ligand with the host erythrocyte occurs through its two regions present at amino acid positions 167-178 (P

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