4,207 research outputs found
Structure and dynamics of hemimethylated GATC sites Implications for DNA-SeqA recognition
No full textDNA methylation occurs in most organisms from bacteria to mammals and provides a mechanism for epigenetic control of a variety of cellular processes. In Escherichia coli, most of the N-6 positions in adenines found in the sequence GATC are methylated by DNA adenine methyltransferase. After DNA replication, the GATC sites exist transiently in the hemimethylated state, and the specific recognition of these hemimethylated GATC sites is essential for several processes, including sequestration of the site of replication initiation by the SeqA protein, strand discrimination in DNA mismatch repair by the MutH protein, and transcription of several genes. Here, we characterize the solution structure and dynamics of two dodecamer DNA duplexes that each contains a single GATC site in either unmethylated or hemimethylated state. We found that the N-6-methylated adenine of a hemimethylated GATC site undergoes a slow trans-cis interconversion. The release of a tightly bound cation from hemimethylated DNA explains the instability of this structure. In addition, quantitative structural analysis revealed that hemimethylated DNA has unusual backbone structures and a remarkably narrow major groove. These dynamic and structural features provide insights into the specific recognition of hemimethylated GATC sites by the SeqA protein
Shear Behavior and Performance of Deep Beams Reinforced with a Honeycomb Steel Mesh
No full text An experimental study was conducted to investigate the structural behavior and performance of deep beams reinforced in shear with a honeycomb steel mesh (HSM). A series of four-point loading tests on five simply supported deep beams were carried out. The control beam was substantially deficient in shear strength, another beam was fully reinforced in shear by stirrups, and four other beams were reinforced with various configurations of HSM. The primary variables were the diagonal cell width and welding condition of the HSM. The shear behavior and performance of deep beams reinforced with various configurations of HSM were compared with those of the control beam and the beam reinforced in shear by stirrups. In this study, all of the tested deep beams failed in shear. Crack patterns and failure modes of the specimens were explained on the basis of the arch action. It was found from the test results that HSM was effective in reinforcing deep beams in shear. Further, the butt- welded HSM with a diagonal cell width of 100 mm was shown to be most effective in terms of stiffness, load carrying, and energy absorption capacities. </jats:p
Behavior and performance of RC T-section deep beams externally strengthened in shear with CFRP sheets
No full textA series of experimental tests were carried out to investigate the behavior and performance of reinforced concrete (RC) T-section deep beams strengthened in shear with CFRP sheets Key variables evaluated in this study were strengthening length, fiber direction combination of CFRP sheets, and an anchorage using U-wrapped CFRP sheets A total of 14 RC T-section deep beams were designed to be deficient in shear with a shear span-to-effective depth ratio (aid) of 1 22 Crack patterns and behavior of the tested deep beams were observed during four-point loading tests Except the CS-FL-HP specimen almost all strengthened deep beams showed a shear-compression failure due to partial delamination of the CFRP sheets From the load-displacement (p-u) curves the effects of key variables on the shear performance of the strengthened deep beams were addressed It was concluded from the test results that the key variables of strengthening length fiber direction combination and anchorage have significant influence on the shear performance of strengthened deep beams In addition a series of comparative studies between the present experimental data and theoretical results in accordance with the commonly applied design codes were made to evaluate the shear strength of a control beam and deep beams strengthened with CFRP sheets (C) 2010 Elsevier Ltd All rights reserve
Structural features of an influenza virus promoter and their implications for viral RNA synthesis
No full textThe influenza A virus, a severe pandemic pathogen, has a segmented RNA genome consisting of eight single-stranded RNA molecules. The 5 ' and 3 ' ends of each RNA segment recognized by the influenza A virus RNA-dependent RNA polymerase direct both transcription and replication of the virus's RNA genome. Promoter binding by the viral RNA polymerase and formation of an active open complex are prerequisites for viral replication and proliferation. Here, we describe the solution structure of this promoter as solved by multidimensional, heteronuclear magnetic resonance spectroscopy. Our studies show that the viral promoter has a significant dynamic nature and reveal an unusual displacement of an adenosine that forms a novel (A-A).U motif and a C-A mismatch stacked in a, helix. The characterized structural features of the promoter imply that the specificity of polymerase binding results from an internal RNA loop. In addition, an unexpected bending (46 +/- 10 degrees) near the initiation site suggests the existence of a promoter recognition mechanism similar to that of DNA-dependent,RNA polymerase and a possible regulatory function for the terminal structure during open complex formation
A single-nucleotide natural variation (U4 to C4) in an influenza A virus promoter exhibits a large structural change: implications for differential viral RNA synthesis by RNA-dependent RNA polymerase
No full textThe influenza A virus promoter is recognized by the influenza A virus RNA-dependent RNA polymerase, and directs both transcription and replication of the viral RNA genome. Within the sequence of this promoter, flu strains exhibit a natural, unique variation, either a U or a C, at the fourth position from the 3' end. Promoters that contain a C residue (C4 promoter), which are invariably found in genome segments that encode the three RNA polymerase subunits (PB1, PB2 and PA), down-regulate transcription but activate genome replication. Here, we have determined the structure of the C4 promoter by NMR spectroscopy and compared it with the structure of the U4 promoter, which was determined previously. The structure of the internal loop in the C4 promoter is similar to that of the U4 promoter. However, the terminal stem of the C4 promoter is strikingly different from that of the U4 promoter. These structural data suggest that the internal loop is important for polymerase binding to the promoter, and the terminal stem is crucial for differential regulation of transcription and replication
Fatty liver, insulin resistance and obesity: relationships with increase in coronary artery calcium over time
No full textBackground: Non alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and obesity frequently co-exist with type 2 diabetes but it is uncertain whether these risk factors for vascular disease contribute to a change in at herosclerosis over time, independently of diabetes status. We tested whether the combination of fatty liver, IR and obesity was associated with an increase in coronary artery calcium (CAC) score over time, independently of diabetes status, other cardiovascular risk factors and medications. Methods: Data were analysed from a South Korean occupational cohort of 2175 people. The outcome was increase in cardiac computed tomography (CT) CAC score between baseline and follow up. IR was defined by HOMA-IR?75th centile and fatty liver by ultrasound. Hazard ratios (HR) [95% confidence intervals (CIs)] were estimated using Cox proportional hazards regression. Results: There were 592 (27.2%) participants in whom CAC score increased from baseline (mean±SD age at baseline 44.8±5.5 years) and 1583 subjects in whom CAC did not change or improved during follow up (mean±SD age 41.6± 5.6 years). Diabetes, HOMA-IR, fatty liver and obesity prevalence were all higher (all p<0.001), in participants in whom CAC score increased from baseline. Adjusting for diabetes and potential confounders, the combination of IR, obesity and fatty liver was independently associated with increase in CAC score over time [(HR 2.46, (95%CIs 1.50,4.03)]. Conclusions: The combination of fatty liver, IR and obesity is associated with progression of atherosclerosis over time independently of diabetes, cardiovascular risk factors, and all medications for cardiovascular disease and diabete
Wellesly Sh. W. to Mr. James Meredith (2 October 1962)
No full textSigned by Wellesly Sh. W.https://egrove.olemiss.edu/mercorr_pro/1531/thumbnail.jp
A comparative study of perchlorate degradation in acute toxicity and chronic toxicity
No full textSince the discovery of perchlorate in water system, the public has been concerned about its human health effect. In practice it was reported that chronic exposure to perchlorate may lead to damage in thyroid hormone activity. This study introduced a method of perchlorate reduction, using autotrophic bacteria which utilise hydrogen as an electron donor. Two experiments were conducted to compare the effects of acute and chronic perchlorate toxicity on bacterial perchlorate reduction potential. One was a batch-fed operation generating acute toxicity and another was a continuous-fed operation generating chronic toxicity. Acclimation period of the batch-fed operation was 14 days while that of the continuous-fed operation was 31 days as commensurate with double. Lots of batch tests using the mixed culture passing through acclimation were conducted to figure out kinetics of biological perchlorate reduction. The maximum perchlorate utilisation rate (qmax) of the mixed culture acclimated by acute toxicity was 2.92 mg ClO4−/mg dry-weight (DW)/d, while that of chronic toxicity was 0.27 mg ClO4−/mg DW/d. Half-maximum rate constants (Ks) of acute and chronic toxicity were 567.3 and 25.6 mg ClO4−/L respectively. This result showed that acute toxicity acclimated the mixed culture more rapidly and produced a higher activity for biological perchlorate reduction than chronic toxicity.</jats:p
Gamma glutamyl transferase is associated with mortality outcomes independently of fatty liver
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