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排序方式: 共有1131条查询结果,搜索用时 281 毫秒
81.
Wagner Sabrina Manickam Ravikumar Brotto Marco Tipparaju Srinivas M. 《Molecular and cellular biochemistry》2022,477(6):1829-1848
Molecular and Cellular Biochemistry - The nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor, involved in various physiological and molecular processes, including energy... 相似文献
82.
83.
Mukund A. Prabhu Narayanan Namboodiri Srinivas Prasad BV S.P. Abhilash Anees Thajudeen Kumar V.K. Ajith 《Indian pacing and electrophysiology journal》2015,15(6):286-290
Background
Electrical storm (ES) is a life threatening emergency. There is little data available regarding acute outcome of ES.Aims
The study aimed to analyze the acute outcome of ES, various treatment modalities used, and the factors associated with mortality.Methods
This is a retrospective observational study involving patients admitted with ES at our centre between 1/1/2007 and 31/12/2013.Results
41 patients (mean age 54.61 ± 12.41 years; 86.7% males; mean ejection fraction (EF) 44.51 ± 16.48%) underwent treatment for ES. Hypokalemia (14.63%) and acute coronary syndrome (ACS) (14.63%) were the commonest identifiable triggers. Only 9 (21.95%) patients already had an ICD implanted. Apart from antiarrhythmic drugs (100%), deep sedation (87.8%), mechanical ventilation (24.39%) and neuraxial modulation using left sympathetic cardiac denervation (21.95%) were the common treatment modalities used. Thirty-three (80.49%) patients could be discharged after a mean duration of 14.2 ± 2.31 days. Eight (19.5%) patients died in hospital. The mortality was significantly higher in those with EF < 35% compared to those with a higher EF (8 (42.11% vs 0 (0%), p = 0.03)). There was no significant difference in mortality between those with versus without a structural heart disease (8 (21.1% vs 0 (0%), p = 0.32)). Comparison of mortality an ACS with ES versus ES of other aetiologies (3 (50%) vs 5 (14.29) %, p = 0.076)) showed a trend towards significance.Conclusion
With comprehensive treatment, there is reasonable acute survival rate of ES. Hypokalemia and ACS are the commonest triggers of ES. Patients with low EF and ACS have higher mortality. 相似文献84.
Stuckey DW Clements M Di-Gregorio A Senner CE Le Tissier P Srinivas S Rodriguez TA 《Development (Cambridge, England)》2011,138(8):1521-1530
During development, the growth of the embryo must be coupled to its patterning to ensure correct and timely morphogenesis. In the mouse embryo, migration of the anterior visceral endoderm (AVE) to the prospective anterior establishes the anterior-posterior (A-P) axis. By analysing the distribution of cells in S phase, M phase and G2 from the time just prior to the migration of the AVE until 18 hours after its movement, we show that there is no evidence for differential proliferation along the A-P axis of the mouse embryo. Rather, we have identified that as AVE movements are being initiated, the epiblast proliferates at a much higher rate than the visceral endoderm. We show that these high levels of proliferation in the epiblast are dependent on Nodal signalling and are required for A-P establishment, as blocking cell division in the epiblast inhibits AVE migration. Interestingly, inhibition of migration by blocking proliferation can be rescued by Dkk1. This suggests that the high levels of epiblast proliferation function to move the prospective AVE away from signals that are inhibitory to its migration. The finding that initiation of AVE movements requires a certain level of proliferation in the epiblast provides a mechanism whereby A-P axis development is coordinated with embryonic growth. 相似文献
85.
G. R. Rao Arun K. Shanker I. Srinivas G. R. Korwar B. Venkateswarlu 《Trees - Structure and Function》2011,25(4):725-734
A thorough and extensive wild germplasm exploration survey was undertaken and 50 high yielding candidate plus trees (CPTs)
of Pongamia pinnata (L.) Pierre from different locations from a latitudinal and longitudinal spread between 12°41′ and 22°E longitude and 77°
and 84°40′N latitude covering 11 locations in an area spread of 150,000 km2 were collected for evaluating genetic association and variability in seed and growth characters. There were significant differences
observed in seed morphology and oil content as was in plant height, and number of branches in the progeny trial. Plant height
and number of branches exhibited much higher values of both phenotypic and genotypic variance than observed in the seed characters.
Among seed characters oil content exhibited highest broad sense heritability of more than 93% followed by seed length (90.0%).
In contrast seed width showed the second highest genetic advance of 5.64% following the highest genetic advance of 10.15%
exhibited by oil content. Hierarchical clustering by Ward’s Minimum Variance Cluster Analysis method showed phylogeographic
patterns of genetic diversity. K means clustering revealed that trees from different geographic regions were grouped together
in a cluster and as were trees from the same geographical area placed in different clusters suggesting that geographical diversity
did not go hand in hand with genetic diversity. In addition clustering identified promising accessions with favourable traits
for future establishment of orchards. 相似文献
86.
Jackson RW LaPorte MG Herbertz T Draper TL Gaboury JA Rippin SR Patel R Chunduru SK Benetatos CA Young DC Burns CJ Condon SM 《Bioorganic & medicinal chemistry letters》2011,21(11):3227-3231
We describe the structure-activity relationship of the C7-position of pyrano[3,4-b]indole-based inhibitors of HCV NS5B polymerase. Further exploration of the allosteric binding site led to the discovery of the significantly more potent compounds 13 and 14. 相似文献
87.
McGuigan C Madela K Aljarah M Gilles A Battina SK Ramamurty CV Srinivas Rao C Vernachio J Hutchins J Hall A Kolykhalov A Henson G Chamberlain S 《Bioorganic & medicinal chemistry letters》2011,21(19):6007-6012
We have previously reported the power of combining a 5'-phosphoramidate ProTide, phosphate pro-drug, motif with a 6-methoxy purine pro-drug entity to generate highly potent anti-HCV agents, leading to agents in clinical trial. We herein extend this work with the disclosure that a variety of alternative 6-substituents are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads, and in almost every case the ProTide is several orders of magnitude more potent than the parent nucleoside. We also demonstrate that these agents act as pro-drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use of hepatocyte cell lysate as an ex vivo model for ProTide metabolism. 相似文献
88.
Fan X Zhang FH Al-Safi RI Zeng LF Shabaik Y Debnath B Sanchez TW Odde S Neamati N Long YQ 《Bioorganic & medicinal chemistry》2011,19(16):4935-4952
HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well mechanistically different. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC(50)=5 μM) with more than 40-fold selectivity for the strand transfer over the 3'-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC(50) value of 8 μM. Using molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. Furthermore, the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site on IN. This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors. 相似文献
89.
Mollapour M Tsutsumi S Truman AW Xu W Vaughan CK Beebe K Konstantinova A Vourganti S Panaretou B Piper PW Trepel JB Prodromou C Pearl LH Neckers L 《Molecular cell》2011,41(6):672-681
Heat shock protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by cochaperones but also by distinct posttranslational modifications. We report here that casein kinase 2 phosphorylates a conserved threonine residue (T22) in α helix-1 of the yeast Hsp90 N-domain both in?vitro and in?vivo. This α helix participates in?a hydrophobic interaction with the catalytic loop in Hsp90's middle domain, helping to stabilize the chaperone's ATPase-competent state. Phosphomimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function and impacts interaction with the cochaperones Aha1 and Cdc37. Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants. 相似文献
90.
Shivaji S Pratibha MS Sailaja B Hara Kishore K Singh AK Begum Z Anarasi U Prabagaran SR Reddy GS Srinivas TN 《Extremophiles : life under extreme conditions》2011,15(1):1-22
Three 16S rRNA gene clone libraries (P1L, P4L and P8L) were constructed using three soil samples (P1S, P4S and P8S) collected
near Pindari glacier, Himalayas. The three libraries yielded a total of 703 clones. Actinobacteria, Firmicutes and Proteobacteria were common to the three libraries. In addition to the above P1L and P8L shared the phyla Acidobacteria, Bacteroidetes, Gemmatimonadetes and Planctomycetes. Phyla Chlamydiae, Chlorobi, Chloroflexi, Dictyoglomi, Fibrobacteres, Nitrospirae, Verrucomicrobia, candidate division SPAM and candidate TM7s TM7a phylum were present only in P1L. Rarefaction analysis indicated that the
bacterial diversity in P4S and P8S soil samples was representative of the sample. Principal component analysis (PCA) revealed
that P1S and P8S were different from P4S soil sample. PCA also indicated that arsenic content, pH, Cr and altitude influence
the observed differences in the percentage of specific OTUs in the three 16S rRNA gene clone libraries. The observed bacterial
diversity was similar to that observed for other Himalayan and non-polar cold habitats. A total of 40 strains of bacteria
were isolated from the above three soil samples and based on the morphology 20 bacterial strains were selected for further
characterization. The 20 bacteria belonged to 12 different genera. All the isolates were psychro-, halo- and alkalitolerant.
Amylase and urease activities were detected in majority of the strains but lipase and protease activities were not detected.
Long chain, saturated, unsaturated and branched fatty acids were predominant in the psychrotolerant bacteria. 相似文献