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Search Results: 1 - 10 of 858 matches for " Raina Dua "
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Cellular phosphatases facilitate combinatorial processing of receptor-activated signals
Dhiraj Kumar, Raina Dua, Ravichandran Srikanth, Shilpi Jayaswal, Zaved Siddiqui, Kanury VS Rao
BMC Research Notes , 2008, DOI: 10.1186/1756-0500-1-81
Abstract: To address the above question we, in the present study, examined the dynamics of signaling from the B cell antigen receptor (BCR) under conditions where individual cellular phosphatases were selectively depleted by siRNA. Results from such experiments revealed a highly enmeshed structure for the signaling network where each signaling node was linked to multiple phosphatases on the one hand, and each phosphatase to several nodes on the other. This resulted in a configuration where individual signaling intermediates could be influenced by a spectrum of regulatory phosphatases, but with the composition of the spectrum differing from one intermediate to another. Consequently, each node differentially experienced perturbations in phosphatase activity, yielding a unique fingerprint of nodal signals characteristic to that perturbation. This heterogeneity in nodal experiences, to a given perturbation, led to combinatorial manipulation of the corresponding signaling axes for the downstream transcription factors.Our cumulative results reveal that it is the tight integration of phosphatases into the signaling network that provides the plasticity by which perturbation-specific information can be transmitted in the form of a multivariate output to the downstream transcription factor network. This output in turn specifies a context-defined response, when translated into the resulting gene expression profile.Reciprocal regulation of protein phosphorylation by kinases and phosphatases represents a key aspect of signal transduction [1-6]. Although information on the role of phosphatases in regulating individual signaling modules continues to accumulate, a larger perspective on how these various interactions integrate to contribute towards signal processing is lacking [7-9]. To explore this we examined the dynamics of signaling from the B cell antigen receptor (BCR) under conditions where individual cellular phosphatases were selectively depleted by siRNA. We found that each phosphat
Defining the antigen receptor-dependent regulatory network that induces arrest of cycling immature B-lymphocytes
Mohammad Jamal, Srikanth Ravichandran, Noor Jailkhani, Samrat Chatterjee, Raina Dua, Kanury VS Rao
BMC Systems Biology , 2010, DOI: 10.1186/1752-0509-4-169
Abstract: Here we employed a systems biology approach that combined extensive experimentation with in silico methodologies to chart the network of receptor-activated pathways that mediated the arrest of immature B cells in the G1 phase of the cell cycle. Interestingly, we found that only a sparse network of signaling intermediates was recruited upon engagement of the antigen receptor. This then led to the activation of a restricted subset of transcription factors, with the consequent induction of genes primarily involved in the cell death pathway. Subsequent experiments revealed that the weak initiation of intracellular signaling pathways derived from desensitization of the receptor-proximal protein tyrosine kinase Lyn, to receptor-dependent activation. Intriguingly, the desensitization was a result of the constitutive activation of this kinase in unstimulated cells, which was likely maintained through a regulatory feedback loop involving the p38 MAP kinase. The high basal activity then attenuated the ability of the antigen receptor to recruit Lyn, and thereby also the downstream signaling intermediates. Finally, integration of these results into a mathematical model provided further substantiation to the novel finding that the ground state of the intracellular signaling machinery constitutes an important determinant of the outcome of receptor-induced cellular responses.Our results identify the global events leading to the G1 arrest and subsequent apoptosis in immature B cells upon receptor activation.Cellular responses to environmental cues are mediated through activation of the signal transduction machinery. This machinery is best represented as a complex network that, in turn, governs the decision-making capabilities of the cell [1,2]. Engagement of a cell surface receptor induces activation of signal transduction cascades that involve a series of phosphorylation/dephosphorylation events. These phosphorylation-dependent signaling events eventually transduce signal to trans
Integration of a Phosphatase Cascade with the MAP Kinase Pathway provides for a Novel Signal Processing Function
Virendra K. Chaudhri,Dhiraj Kumar,Manjari Misra,Raina Dua,Kanury V. S. Rao
Quantitative Biology , 2009, DOI: 10.1074/jbc.M109.055863
Abstract: We mathematically modeled the receptor-activated MAP kinase signaling by incorporating the regulation through cellular phosphatases. Activation induced the alignment of a phosphatase cascade in parallel with the MAP kinase pathway. A novel regulatory motif was thus generated, providing for the combinatorial control of each MAPK intermediate. This ensured a non-linear mode of signal transmission with the output being shaped by the balance between the strength of input signal, and the activity gradient along the phosphatase axis. Shifts in this balance yielded modulations in topology of the motif, thereby expanding the repertoire of output responses. Thus we identify an added dimension to signal processing, wherein the output response to an external stimulus is additionally filtered through indicators that define the phenotypic status of the cell.
Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen
Shilpi Jayaswal,Md. Azhar Kamal,Raina Dua,Shashank Gupta,Tanmay Majumdar,Gobardhan Das,Dhiraj Kumar ,Kanury V. S. Rao
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1000839
Abstract: The stable infection of host macrophages by Mycobacterium tuberculosis (Mtb) involves, and depends on, the attenuation of the diverse microbicidal responses mounted by the host cell. This is primarily achieved through targeted perturbations of the host cellular signaling machinery. Therefore, in view of the dependency of the pathogen on host molecules for its intracellular survival, we wanted to test whether targeting such factors could provide an alternate route for the therapeutic management of tuberculosis. To first identify components of the host signaling machinery that regulate intracellular survival of Mtb, we performed an siRNA screen against all known kinases and phosphatases in murine macrophages infected with the virulent strain, H37Rv. Several validated targets could be identified by this method where silencing led either to a significant decrease, or enhancement in the intracellular mycobacterial load. To further resolve the functional relevance of these targets, we also screened against these identified targets in cells infected with different strains of multiple drug-resistant mycobacteria which differed in terms of their intracellular growth properties. The results obtained subsequently allowed us to filter the core set of host regulatory molecules that functioned independently of the phenotypic variations exhibited by the pathogen. Then, using a combination of both in vitro and in vivo experimentation, we could demonstrate that at least some of these host factors provide attractive targets for anti-TB drug development. These results provide a “proof-of-concept” demonstration that targeting host factors subverted by intracellular Mtb provides an attractive and feasible strategy for the development of anti-tuberculosis drugs. Importantly, our findings also emphasize the advantage of such an approach by establishing its equal applicability to infections with Mtb strains exhibiting a range of phenotypic diversifications, including multiple drug-resistance. Thus the host factors identified here may potentially be exploited for the development of anti-tuberculosis drugs.
miR-24-2 controls H2AFX expression regardless of gene copy number alteration and induces apoptosis by targeting antiapoptotic gene BCL-2: a potential for therapeutic intervention
Niloo Srivastava, Siddharth Manvati, Archita Srivastava, Ranjana Pal, Ponnusamy Kalaiarasan, Shilpi Chattopadhyay, Sailesh Gochhait, Raina Dua, Rameshwar NK Bamezai
Breast Cancer Research , 2011, DOI: 10.1186/bcr2861
Abstract: Changes in gene copy number and mRNA/miR expression were estimated using real-time polymerase chain reaction assays in two mammalian cell lines, MCF-7 and HeLa, and in a set of sporadic breast cancer tissues. In silico analysis was performed to find the putative target for miR-24-2. MCF-7 cells were transfected with precursor miR-24-2 oligonucleotides, and the gene expression levels of BRCA1, BRCA2, ATM, MDM2, TP53, CHEK2, CYT-C, BCL-2, H2AFX and P21 were examined using TaqMan gene expression assays. Apoptosis was measured by flow cytometric detection using annexin V dye. A luciferase assay was performed to confirm BCL-2 as a valid cellular target of miR-24-2.It was observed that H2AX gene expression was negatively correlated with miR-24-2 expression and not in accordance with the gene copy number status, both in cell lines and in sporadic breast tumor tissues. Further, the cells overexpressing miR-24-2 were observed to be hypersensitive to DNA damaging drugs, undergoing apoptotic cell death, suggesting the potentiating effect of mir-24-2-mediated apoptotic induction in human cancer cell lines treated with anticancer drugs. BCL-2 was identified as a novel cellular target of miR-24-2.mir-24-2 is capable of inducing apoptosis by modulating different apoptotic pathways and targeting BCL-2, an antiapoptotic gene. The study suggests that miR-24-2 is more effective in controlling H2AX gene expression, regardless of the change in gene copy number. Further, the study indicates that combination therapy with miR-24-2 along with an anticancer drug such as cisplatin could provide a new avenue in cancer therapy for patients with tumors otherwise resistant to drugs.Copy number variations (CNVs) are ubiquitous in nature and have been identified in diverse species, including humans [1], monkeys [2], rats [3], mice [4] and Drosophila [5]. Advancement in DNA array technology has led to the discovery of CNVs that are now believed to cover at least 10% of the total human genome [6]. In
Fuzzy vs. Probabilistic Techniques to Address Uncertainty for Radial Distribution Load Flow Simulation  [PDF]
Roma Raina, Mini Thomas
Energy and Power Engineering (EPE) , 2012, DOI: 10.4236/epe.2012.42014
Abstract: For Power distribution system the most important task for distribution engineer is to efficiently simulate the system and address the uncertainty using a suitable mathematical method. This paper presents a comparison of two methods used in analyzing uncertainties. The first method is Montecarlo simulation (MCS) that considers input parameters as random variables and second one is fuzzy alpha cut method (FAC) in which uncertain parameters are treated as fuzzy numbers with given membership functions. Both techniques are tested on a typical Load flow solution simulation, where connected loads are considered as uncertain. In order to provide a basis for comparison between above two approaches, the shapes of the membership function used in the fuzzy method is taken same as the shape of the probability density function used in the Monte Carlo simulations. For more than one uncertain input variable, simulation result indicates that MCS method provides better output results compared to FAC, however takes more time due to number of runs. FAC provides an alternate method to MCS when addressing single or limited input variables and is fast.
Elderly vaccination—The glass is half full  [PDF]
Chandini Raina MacIntyre
Health (Health) , 2013, DOI: 10.4236/health.2013.512A011

The shifting global demography and ageing of populations worldwide brings with new challenges for the health care, and an imperative for healthy ageing and preventive health strategies for adults. Immunization is the low hanging fruit for healthy ageing, and yet under-utilized for various reasons, including waning immunity in the elderly, lack of RCT data in this age group, and lack of provider confidence in vaccines for the elderly. The elderly people have a higher incidence of infection and more severe and serious consequences of infection. Diseases such as influenza, pneumococcal disease and herpes zoster have long been recognized as causing a high burden in the elderly, but evidence is also emerging for other infections such as pertussis being a major cause of the morbidity in this age group. Now, there are several vaccines which can prevent major infectious diseases in the elderly. To improve uptake of these vaccines, elderly vaccination should be viewed through a different lens to pediatric vaccination, accepting that vaccines are less immunogenic in the elderly. The population health impact of vaccines in the elderly, despite of immunosenescence and lower immunogenicity, is still likely to be high given the increased disease incidence. Vaccination is an important and readily available means of prevention in the elderly.

Impact Of Chlorpyriphos On The Morphological Parameters Of Cauliflower, Tomato And Okra
Mosmi Raina,Anil Raina
Indian Streams Research Journal , 2012,
Abstract: The present study has been conducted to work out the effect of a wide spectrum organophosphorous insecticide, chlorpyriphos (O, O-Diethyl O- 3, 5, 6-trichloro-2-pyridyl phosphorothioate) on the morphological features of three commonly grown vegetables in the study area i.e. Cauliflower (Brassica oleracea L. var. botrytis, Variety: Snowball 16), Tomato (Lycopersicon esculentum Mill., Variety: Pusa Ruby) and Okra (Abelmoschus esculentus L., Variety: Pusa Sawani). Results revealed that on an average, the impact of chlorpyriphos on various morphological parameters of all the three vegetables have been statistically insignificant (using t- Test) except for height of the plants in cauliflower treated with double the recommended dose which exhibited a significant decrease and weight of the head in cauliflower treated with recommended dose of chlorpyriphos which showed a significant increase. Also in okra total number of flowers/plant at treatment with both the dosages along with total number of fruits/plant at treatment with the recommended dose has exhibited statistically significant increase.
El mito político de la RDA
Raina Zimmering
Revista mexicana de ciencias políticas y sociales , 2001,
Presidential address
Raina V
Journal of Indian Association of Pediatric Surgeons , 2009,
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