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Anuradha Kalani Pradip K. Kamat Michael J. Voor Suresh C. Tyagi Neetu Tyagi 《Molecular and cellular biochemistry》2014,393(1-2):89-98
The studies into the pathophysiology of viral miRNAs are still in infancy; the interspecies regulation at the miRNA level fuels the spark of the investigation into the repertoire of virus–host interactions. Reports pertaining to the viral miRNAs role in modulating/evading the host immune response are surging up; we initiated this in silico study to speculate the role of human cytomegalovirus (HCMV)-encoded miRNAs on human antiviral mechanisms such as apoptosis and autophagy. The results indicate that both the above mechanisms were targeted by the HCMV miRNAs, located in the unique long region of the HCMV genome. The proapoptotic genes MOAP1, PHAP, and ERN1 are identified to be the potential targets for the miR-UL70-3p and UL148D, respectively. The ERN1 gene plays a role in the initiation of Endoplasmic reticulum stress-induced apoptosis as well as autophagosome formation. This study shows that HCMV employs its miRNA repertoire for countering the cellular apoptosis and autophagy, particularly the mitochondrial-dependent intrinsic pathway of apoptosis. In addition, the homology studies reveal no HCMV miRNA bears sequence homology with human miRNAs. 相似文献
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ARRY‐334543 Reverses Multidrug Resistance by Antagonizing the Activity of ATP‐Binding Cassette Subfamily G Member 2
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Background: The fatty-acid profile of the vegetable oils determines its properties and nutritional value. Palm-oil obtained from the
African oil-palm [Elaeis guineensis Jacq. (Tenera)] contains 44% palmitic acid (C16:0), but, palm-oil obtained from the American oilpalm
[Elaeis oleifera] contains only 25% C16:0. In part, the b-ketoacyl-[ACP] synthase II (KASII) [EC: 2.3.1.179] protein is responsible
for the high level of C16:0 in palm-oil derived from the African oil-palm. To understand more about E. guineensis KASII (EgKASII)
and E. oleifera KASII (EoKASII) proteins, it is essential to know its structures. Hence, this study was undertaken. Objective: The
objective of this study was to predict three-dimensional (3D) structure of EgKASII and EoKASII proteins using molecular
modelling tools. Materials and Methods: The amino-acid sequences for KASII proteins were retrieved from the protein database of
National Center for Biotechnology Information (NCBI), USA. The 3D structures were predicted for both proteins using homology
modelling and ab-initio technique approach of protein structure prediction. The molecular dynamics (MD) simulation was
performed to refine the predicted structures. The predicted structure models were evaluated and root mean square deviation
(RMSD) and root mean square fluctuation (RMSF) values were calculated. Results: The homology modelling showed that EgKASII
and EoKASII proteins are 78% and 74% similar with Streptococcus pneumonia KASII and Brucella melitensis KASII, respectively. The
EgKASII and EoKASII structures predicted by using ab-initio technique approach shows 6% and 9% deviation to its structures
predicted by homology modelling, respectively. The structure refinement and validation confirmed that the predicted structures
are accurate. Conclusion: The 3D structures for EgKASII and EoKASII proteins were predicted. However, further research is
essential to understand the interaction of EgKASII and EoKASII proteins with its substrates. 相似文献
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Andrew S. Cutting Yvette Del Rosario Rong Mu Anthony Rodriguez Andreas Till Suresh Subramani Roberta A. Gottlieb Kelly S. Doran 《The Journal of biological chemistry》2014,289(52):35711-35723
Bacterial meningitis occurs when bloodborne pathogens invade and penetrate the blood-brain barrier (BBB), provoking inflammation and disease. Group B Streptococcus (GBS), the leading cause of neonatal meningitis, can enter human brain microvascular endothelial cells (hBMECs), but the host response to intracellular GBS has not been characterized. Here we sought to determine whether antibacterial autophagy, which involves selective recognition of intracellular organisms and their targeting to autophagosomes for degradation, is activated in BBB endothelium during bacterial infection. GBS infection resulted in increased punctate distribution of GFP-microtubule-associated protein 1 light chain 3 (LC3) and increased levels of endogenous LC3-II and p62 turnover, two hallmark indicators of active autophagic flux. Infection with GBS mutants revealed that bacterial invasion and the GBS pore-forming β-hemolysin/cytolysin (β-h/c) trigger autophagic activation. Cell-free bacterial extracts containing β-h/c activity induced LC3-II conversion, identifying this toxin as a principal provocative factor for autophagy activation. These results were confirmed in vivo using a mouse model of GBS meningitis as infection with WT GBS induced autophagy in brain tissue more frequently than a β-h/c-deficient mutant. Elimination of autophagy using Atg5-deficient fibroblasts or siRNA-mediated impairment of autophagy in hBMECs led to increased recovery of intracellular GBS. However, electron microscopy revealed that GBS was rarely found within double membrane autophagic structures even though we observed GBS-LC3 co-localization. These results suggest that although autophagy may act as a BBB cellular defense mechanism in response to invading and toxin-producing bacteria, GBS may actively thwart the autophagic pathway. 相似文献
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Taras Y. Nazarko Katharine Ozeki Andreas Till Geetha Ramakrishnan Pouya Lotfi Mingda Yan Suresh Subramani 《The Journal of cell biology》2014,206(4):541-557
Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3′,5′-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 105 GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces “molecule noise.” Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons. 相似文献