Design and Fabrication of a Retractable Bridge

Volume 7 Issue 12 (December 201

Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis

Hepatitis C virus (HCV)-mediated liver diseases are one of the major health issues in the United States and worldwide. HCV infection has been reported to modulate microRNAs (miRNAs) that control various cell surface receptors and gene-regulatory complexes involved in hepatic inflammation and liver diseases. We report here that specific downregulation of miRNA-107 and miRNA-449a following HCV infection in patients with HCV-mediated liver diseases modulates expression of CCL2, an inflammatory chemokine upregulated in patients with chronic liver diseases, by targeting components of the interleukin-6 receptor (IL-6R) complex. Computational analysis for DNA-bound transcription factors in the CCL2 promoter identified adjacent binding sites for CCAAT/CEBPα, spleen focus-forming virus, proviral integration oncogene (SPI1/PU.1), and STAT3. We demonstrate that CEBPα, PU.1, and STAT3 interacted with each other physically to cooperatively bind to the promoter and activate CCL2 expression. Analysis of IL-6R and JAK1 expression in HCV patients by quantitative PCR showed significant upregulation when there was impaired miRNA-107 and miRNA-449a expression, along with upregulation of PU.1 and STAT3, but not CEBPα. miRNA-449a and miRNA-107 target expression of IL-6R and JAK1, respectively, in vitro and also inhibit IL-6 signaling and impair STAT3 activation in human hepatocytes. Taken together, our results demonstrate a novel gene-regulatory mechanism in which HCV-induced changes in miRNAs (miRNA-449a and miRNA-107) regulate CCL2 expression by activation of the IL-6-mediated signaling cascade, which we propose will result in HCV-mediated induction of inflammatory responses and fibrosis. IMPORTANCE Hepatitis C virus (HCV)-induced hepatitis is a major health concern worldwide. HCV infection results in modulation of noncoding microRNAs affecting major cellular pathways, including inflammatory responses. In this study, we have identified a microRNA-regulated pathway for the chemokine CCL2 in HCV-induced hepatitis. Understanding microRNA-mediated transcriptional-regulatory pathways will result in development of noninvasive biomarkers for better disease prediction and development of effective therapeutics

Tectonic structure, evolution, and the nature of oceanic core complexes and their detachment fault zones (13°20′N and 13°30′N, Mid Atlantic Ridge)

Microbathymetry data, in situ observations, and sampling along the 138200N and 138200N oceanic core complexes (OCCs) reveal mechanisms of detachment fault denudation at the seafloor, links between tectonic extension and mass wasting, and expose the nature of corrugations, ubiquitous at OCCs. In the initial stages of detachment faulting and high-angle fault, scarps show extensive mass wasting that reduces their slope. Flexural rotation further lowers scarp slope, hinders mass wasting, resulting in morphologically complex chaotic terrain between the breakaway and the denuded corrugated surface. Extension and drag along the fault plane uplifts a wedge of hangingwall material (apron). The detachment surface emerges along a continuous moat that sheds rocks and covers it with unconsolidated rubble, while local slumping emplaces rubble ridges overlying corrugations. The detachment fault zone is a set of anostomosed slip planes, elongated in the alongextension direction. Slip planes bind fault rock bodies defining the corrugations observed in microbathymetry and sonar. Fault planes with extension-parallel stria are exposed along corrugation flanks, where the rubble cover is shed. Detachment fault rocks are primarily basalt fault breccia at 138200N OCC, and gabbro and peridotite at 138300N, demonstrating that brittle strain localization in shallow lithosphere form corrugations, regardless of lithologies in the detachment zone. Finally, faulting and volcanism dismember the 138300N OCC, with widespread present and past hydrothermal activity (Semenov fields), while the Irinovskoe hydrothermal field at the 138200N core complex suggests a magmatic source within the footwall. These results confirm the ubiquitous relationship between hydrothermal activity and oceanic detachment formation and evolution

BoBBLE: ocean-atmosphere interaction and its impact on the South Asian monsoon

The Bay of Bengal (BoB) plays a fundamental role in controlling the weather systems that make up the South Asian summer monsoon system. In particular,the southern BoB has cooler sea surface temperature (SST) that influence ocean-atmosphere interaction and impact on the monsoon. Compared to the southeast, the southwestern BoB is cooler, more saline, receives much less rain, and is influenced by the Summer Monsoon Current(SMC). To examine the impact of these features on the monsoon, the BoB Boundary Layer Experiment (BoBBLE) was jointly undertaken by India and the UK during June–July 2016. Physical and bio-geochemical observations were made using a CTD, five ocean gliders, a uCTD, a VMP, two ADCPs, Argo floats, drifting buoys, meteorological sensors and upper air radiosonde balloons. The observations were made along a zonal section at 8◦N between 85.3◦E and 89◦E with a 10-day time series at 89◦E, 8◦N. This paper presents the new observed features of the southern BoB from the BoBBLE field program, supported by satellite data. Key results from the BoBBLE field campaign show the Sri Lanka Dome and the SMC in different stages of their seasonal evolution and two freshening events during which salinity decreased in the upper layer leading to the formation of thick barrier layers. BoBBLE observations were taken during a suppressed phase of the intraseasonal oscillation; they captured in detail the warming of the ocean mixed layer and preconditioning of the atmosphere to convection

Perspectives in visual imaging for marine biology and ecology: from acquisition to understanding

Durden J, Schoening T, Althaus F, et al. Perspectives in Visual Imaging for Marine Biology and Ecology: From Acquisition to Understanding. In: Hughes RN, Hughes DJ, Smith IP, Dale AC, eds. Oceanography and Marine Biology: An Annual Review. 54. Boca Raton: CRC Press; 2016: 1-72

Anastomotic leak management after a low anterior resection leading to recurrent abdominal compartment syndrome: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Low anterior resection is usually the procedure of choice for rectal cancer, but a series of complications often accompany this procedure. This case report describes successful management of an intricate anastomotic leak after a low anterior resection.</p> <p>Case presentation</p> <p>A 66-year-old Caucasian man was admitted to our hospital and diagnosed with a low rectal adenocarcinoma. He underwent a low anterior resection but subsequently developed fecal peritonitis due to an anastomotic leak. He was operated on again but developed abdominal compartment syndrome, multi-organ failure and sepsis. He was aggressively treated in the intensive care unit and in the operating room. Overall, the patient underwent four laparotomies and stayed in the intensive care unit for 75 days. He was discharged after 3 months of hospitalization.</p> <p>Conclusion</p> <p>Abdominal compartment syndrome may present as a devastating complication of damage control laparotomy. Prompt recognition and goal-directed management are the cornerstones of treatment.</p

SYNTHESIS, CHARACTERISATION AND EVALUATION OF SOME 1,5-BENZODIAZEPINE QUINOLIN-2-ONE DERIVATIVES AS POSSIBLE HYPNOTIC AGENTS.

A series of novel 3-(2-(phenyl/substituted phenyl)-1H-benzo[b] [1,5]-diazepin-4-yl)-4-methoxy-1-phenyl/methylquinolin-2(1H)-one [IV-a(1-6)/IV-b(1-6)] derivatives were synthesised by condensation of 3-substituted cinnamoyl-4-methoxy-1-phenyl/methylquinolin-2(1H)-one [III-a(1-6)/III-b(1-6)] with o-phenylenediamine. The results of the docking studies revealed that the synthesised compounds exhibited well conserved hydrogen bonding with one or more amino acid residues in the active pocket of alpha1beta3gamma2L GABA(A) Receptor (PDB ID: 6HUO) using Molegro Virtual Docker Software (MVD-2013, 6.0). The title compounds exhibited Mol Dock Score in the range of -124.502 to -149.448 with score more or comparable to the standard ligand score of -127.4127 and better than the standard drug -92.3878. All the synthesized compounds were satisfactorily characterized by spectral analysis and were tested for in vivo hypnotic activity based on the potentiation of barbiturate (phenobarbitone) sleeping time in miceusing diazepam as reference standard. All the compounds, except 4-methoxy-1-methyl-3-(2-(3-nitrophenyl)-1H-benzo[b][1,5]-diazepin-4-yl) quinolin-2(1H)-one (IV-b4), significantly decreased the sleep latency, prolonged the duration of sleep and also showed good muscle relaxation property. Among the synthesised compounds, 4-methoxy-3-(2-(3-methoxyphenyl)-1H-benzo[b][1,5]-diazepin-4-yl)-1-phenylquinolin-2(1H)-one (IV-a3) was found to be the most potenthypnotic agentwith sleep latency of 26.67 ± 2.629 min and sleeping time of 111.00 ± 6.028 minutesand matches with pharmacophore mapping of the designed molecule with the MolDock score