Base extrusion is found at helical junctions between right- and left-handed forms of DNA and RNA

Base extrusion is a major structural feature at the junction between B- and Z-DNA (the B–Z junction) where a base pair is broken, and the two bases are extruded from the double helix. Despite the demonstration of base extrusion at the B–Z junction, it is not clear whether a similar base extrusion occurs at other types of junctions involving the left-handed Z conformation. Here, we investigate structural changes of bases at three Z-form junctions: DNA B–Z and Z–Z and RNA A–Z junctions. By monitoring fluorescently labeled duplex nucleic acids using 2-aminopurines at various positions relative to the junction point, we show that base extrusion occurs not only at the DNA B–Z junction, but also at the RNA A–Z and DNA Z–Z junctions. Our data suggest that base extrusion is a general feature of Z-form nucleic-acid junctions.Korean Science and Engineering Foundation (grant NRL-2006-02287)Korea (South). Ministry of Science and Technology (21C Frontier Functional Proteomics Program FPR08B2-270)Korean Science and Engineering Foundation (Ubiquitome Research Program M105 33010001-05N3301-00100)Korea Research Foundation (MOEHRD, Basic Research Promotion Fund; KRF-2005-070-C00078

Effect of blood pressure and glycemic control on the plasma cell-free DNA in hemodialysis patients

AbstractBackgroundThe plasma levels of cell-free DNA (cfDNA) are known to be elevated under inflammatory or apoptotic conditions. Increased cfDNA levels have been reported in hemodialysis (HD) patients. The aim of this study was to investigate the clinical significance of cfDNA in HD patients.MethodsA total of 95 patients on HD were enrolled. We measured their predialysis cfDNA levels using real-time EIF2C1 gene sequence amplification and analyzed its association with certain clinical parameters.ResultsThe mean plasma cfDNA level in the HD patients was 3,884 ± 407 GE/mL, and the mean plasma cfDNA level in the control group was 1,420 ± 121 GE/mL (P < 0.05). Diabetic patients showed higher plasma cfDNA levels compared with nondiabetic patients (P < 0.01). Patients with cardiovascular complications also showed higher plasma cfDNA levels compared with those without cardiovascular complication (P < 0.05). In univariable analysis, the cfDNA level was associated with 3-month mean systolic blood pressure (SBP), white blood cell, serum albumin, creatinine (Cr), normalized protein catabolic rate in HD patients. In diabetic patients, it was significantly correlated with SBP, hemoglobin A1c, and serum albumin. In multivariate analysis, SBP was the independent determinant for the cfDNA level. In diabetic patients, cfDNA level was independently associated with hemoglobin A1c and SBP.ConclusionsIn patients with HD, cfDNA is elevated in diabetic patients and patients with cardiovascular diseases. Uncontrolled hypertension and poor glycemic control are independent determinants for the elevated cfDNA. Our data suggest that cfDNA might be a marker of vascular injury rather than proinflammatory condition in HD patients

Identification of DNA methylation changes associated with human gastric cancer

<p>Abstract</p> <p>Background</p> <p>Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.</p> <p>Methods</p> <p>We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm.</p> <p>Results</p> <p>We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the <it>HOX </it>and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (<it>MDM2</it>, <it>DYRK2</it>, and <it>LYZ</it>) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.</p> <p>Conclusions</p> <p>Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.</p

Practice Pattern of Gastroenterologists for the Management of GERD Under the Minimal Influence of the Insurance Reimbursement Guideline: A Multicenter Prospective Observational Study

The objective of the study was to document practice pattern of gastroenterologists for the management of gastroesophageal reflux disease (GERD) under the minimal influence of the insurance reimbursement guideline. Data on management for 1,197 consecutive patients with typical GERD symptoms were prospectively collected during 16 weeks. In order to minimize the influence of reimbursement guideline on the use of proton pump inhibitors (PPIs), rabeprazole was used for the PPI treatment. A total of 861 patients (72%) underwent endoscopy before the start of treatment. PPIs were most commonly prescribed (87%). At the start of treatment, rabeprazole 20 mg daily was prescribed to 94% of the patients who received PPI treatment and 10 mg daily to the remaining 6%. At the third visits, rabeprazole 20 mg daily was prescribed to 70% of those who were followed and 10 mg daily for the remaining 30%. Continuous PPI treatment during the 16-week period was performed in 63% of the study patients. In conclusion, a full-dose PPI is preferred for the initial and maintenance treatment of GERD under the minimal influence of the insurance reimbursement guideline, which may reflect a high proportion of GERD patients requiring a long-term treatment of a full-dose PPI

Bilateral Spontaneous Perirenal Hemorrhage due to Initial Presentation of Polyarteritis Nodosa

Spontaneous perirenal hemorrhage (SPH) is uncommon but can be a life-threatening condition which is associated with flank or abdominal pain and hypovolemia. The etiologies of SPH include tumor, vascular disease, and infection. Among the vascular diseases, polyarteritis nodosa (PAN) is common cause of the SPH. However, patients with PAN usually complain of nonspecific symptoms and the incidence of PAN is relatively rare. So, diagnosis is difficult even though tissue biopsy and angiography help to confirm the PAN. Particularly bilateral perirenal hemorrhage is very rare complication in patients with PAN. We reported a case of bilateral perirenal hemorrhage in the patients with PAN who have continued to take exogenous sex hormone

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure