03061nas a2200241   4500008004100000022001400041245011700055210006900172260008500241300000900326490000600335520215300341100002002494700002302514700002402537700002402561700002102585700001902606700002002625700002302645700002402668856012702692       2007                        eng d  a1932-620300aAnalysis of mitochondrial DNA sequences in childhood encephalomyopathies reveals new disease-associated variants0 aAnalysis of mitochondrial DNA sequences in childhood encephalomy  a185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USAbPUBLIC LIBRARY SCIENCEcSEP  ae9420 v23 a<p>Background. Mitochondrial encephalomyopathies are a heterogeneous group of clinical disorders generally caused due to mutations in either mitochondrial DNA (mtDNA) or nuclear genes encoding oxidative phosphorylation (OXPHOS). We analyzed the mtDNA sequences from a group of 23 pediatric patients with clinical and morphological features of mitochondrial encephalopathies and tried to establish a relationship of identified variants with the disease. Methodology/Principle Findings. Complete mitochondrial genomes were amplified by PCR and sequenced by automated DNA sequencing. Sequencing data was analyzed by SeqScape software and also confirmed by BLASTn program. Nucleotide sequences were compared with the revised Cambridge reference sequence (CRS) and sequences present in mitochondrial databases. The data obtained shows that a number of known and novel mtDNA variants were associated with the disease. Most of the non-synonymous variants were heteroplasmic (A4136G, A9194G and T11916A) suggesting their possibility of being pathogenic in nature. Some of the missense variants although homoplasmic were showing changes in highly conserved amino acids (T3394C, T3866C, and G9804A) and were previously identified with diseased conditions. Similarly, two other variants found in tRNA genes (G5783A and C8309T) could alter the secondary structure of Cys-tRNA and Lys-tRNA. Most of the variants occurred in single cases; however, a few occurred in more than one case (e. g. G5783A and A10149T). Conclusions and Significance. The mtDNA variants identified in this study could be the possible cause of mitochondrial encephalomyopathies with childhood onset in the patient group. Our study further strengthens the pathogenic score of known variants previously reported as provisionally pathogenic in mitochondrial diseases. The novel variants found in the present study can be potential candidates for further investigations to establish the relationship between their incidence and role in expressing the disease phenotype. This study will be useful in genetic diagnosis and counseling of mitochondrial diseases in India as well as worldwide.</p>1 aWani, Aijaz, A.1 aAhanger, Sajad, H.1 aBapat, Sharmila, A.1 aRangrez, Ashraf, Y.1 aHingankar, Nitin1 aSuresh, C., G.1 aBarnabas, Shama1 aPatole, Milind, S.1 aShouche, Yogesh, S.  uhttp://library.ncl.res.in/content/analysis-mitochondrial-dna-sequences-childhood-encephalomyopathies-reveals-new-disease-002356nas a2200277   4500008004100000022001400041245015900055210006900214260009000283300001200373490000700385520127400392653002401666653002801690653002901718653003401747100002001781700002401801700002001825700002401845700001901869700002001888700002301908700002001931856012701951       2008                        eng d  a1071-576200aAnalysis of reactive oxygen species and antioxidant defenses in complex I deficient patients revealed a specific increase in superoxide dismutase activity0 aAnalysis of reactive oxygen species and antioxidant defenses in   aTELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLANDbINFORMA HEALTHCAREcMAY  a415-4270 v423 a<p>The mechanism of free radical production by complex I deficiency is ill-defined, although it is of significant contemporary interest. This study studied the ROS production and antioxidant defenses in children with mitochondrial NADH dehydrogenase deficiency. ROS production has remained significantly elevated in patients compared to controls. The expression of all antioxidant enzymes significantly increased at mRNA level. However, the enzyme activities did not correlate with high mRNA or protein expression. Only the activity of superoxide dismutase (SOD) was found to correlate with higher mRNA expression in patient derived cell lines. The activities of the enzymes such as glutathione peroxidase (GPx), Catalase (CAT) and glutathione-S-transferase (GST) were significantly reduced in patients (p &lt; 0.05 or p &lt; 0.01). Glutathione reductase (GR) activity and intracellular glutathione (GSH) levels were not changed. Decreased enzyme activities could be due to post-translational or oxidative modification of ROS scavenging enzymes. The information on the status of ROS and marking the alteration of ROS scavenging enzymes in peripheral lymphocytes or lymphoblast cell lines will provide a better way to design antioxidant therapies for such disorders.</p>10aantioxidant enzymes10amitochondrial complex I10amitochondrial myopathies10aReactive Oxygen Species (ROS)1 aWani, Aijaz, A.1 aRangrez, Ashraf, Y.1 aKumar, Himanshu1 aBapat, Sharmila, A.1 aSuresh, C., G.1 aBarnabas, Shama1 aPatole, Milind, S.1 aShouche, Yogesh  uhttp://library.ncl.res.in/content/analysis-reactive-oxygen-species-and-antioxidant-defenses-complex-i-deficient-patients-002071nas a2200205   4500008004100000022001500041245010100056210006900157260000800226300001400234490000800248520136500256100002201621700001901643700001901662700001901681700002501700700002101725856011901746       2018                        eng d  a 0141-813000aActivation of HRI is mediated by Hsp90 during stress through modulation of the HRI-Hsp90 complex0 aActivation of HRI is mediated by Hsp90 during stress through mod  cOCT  a1604-16130 v1183 aHeme Regulated Inhibitor (HRI) is known to get activated in various stresses such as heme deficiency, heat shock, heavy metal toxicity etc. Heat shock protein 90 (Hsp90), a ubiquitous cytoplasmic protein interacts with HRI in order to regulate protein synthesis. However, it still remains to establish this interaction of HRI and Hsp90 at cellular levels and how this modulation of HRI activity is mediated by Hsp90 during stress. In the present report, using co-immunoprecipitation analysis we show that HRI interacts with Hsp90 and this association is independent of other co-chaperones in in vitro conditions. Further, analysis using truncated domains of HRI revealed that the K1 subdomain is essential for HRI - Hsp90 complex formation. Our in silico protein - protein interaction studies also indicated interaction of Hsp90 with K1 subdomain of HRI. Mammalian two hybrid assay validated this HRI - Hsp90 interaction at cellular levels. When the in vitro kinase assay was carried out with the co-immunoprecipitated complex of HRI - Hsp90, an increase in the kinase activity was observed resulting elevated levels of eIF2 alpha phosphorylation upon heavy metal stress and heat shock. Thus, our results clearly indicate modulation of HRI kinase activity with simultaneous Hsp90 association under stress conditions. (C) 2018 Elsevier B.V. All rights reserved.1 aBerwal, Sunil, K.1 aBhatia, Varsha1 aBendre, Arneya1 aSuresh, C., G.1 aChatterjee, Sangeeta1 aPal, Jayanta, K.  uhttp://library.ncl.res.in/content/activation-hri-mediated-hsp90-during-stress-through-modulation-hri-hsp90-complex01871nas a2200157   4500008004100000245009900041210006900140260000800209300001200217490000800229520128800237100002201525700002601547700001901573856012101592       2018                        eng d00aAnalysis of Kunitz inhibitors from plants for comprehensive structural and functional insights0 aAnalysis of Kunitz inhibitors from plants for comprehensive stru  cJUL  a933-9430 v1133 aLegume Kunitz type trypsin inhibitor (KTI) family is one of the most versatile families of proteins. A typical KTI features a single peptide folded in beta-trefoil manner, with the molecular weight about 20-22 kDa and two disulphide bonds. The members are known to inhibit a wide range of serpins proteases at the same time many of them possess unique features. Copaifera langsdoiffii Trypsin inhibitor (CTI) has a beta-trefoil fold made up of two non-covalently bound polypeptide chains with only a single disulfide bridge. Delonix regia Trypsin inhibitor (DrTI) has one amino acid insertion between P1 and P2 of the reactive site distorting its conformation. Bauhinia bauhinioides Cruzipain inhibitor (BbCI) has a conservative beta-trefoil fold but lacks disulfide bonds. Such subtle differences in structures make Kunitz inhibitors different from other inhibitor families. Most of the studies on these inhibitors are focused towards their proposed role in defense from insect pests and wounding but their exact physiological role in nature is still uncharted. Thus, it would be very interesting to closely analyze the structural details of these inhibitors in order to ascertain their biological role and other fascinating applications. (C) 2018 Elsevier B.V. All rights reserved.1 aBendre, Ameya, D.1 aRamasamy, Sureshkumar1 aSuresh, C., G.  uhttp://library.ncl.res.in/content/analysis-kunitz-inhibitors-plants-comprehensive-structural-and-functional-insights