Spatial patterns of transcriptional activity in the chromosome of Escherichia coli

BACKGROUND: Although genes on the chromosome are organized in a fixed order, the spatial correlations in transcription have not been systematically evaluated. We used a combination of genomic and signal processing techniques to investigate the properties of transcription in the genome of Escherichia coli K12 as a function of the position of genes on the chromosome. RESULTS: Spectral analysis of transcriptional series revealed the existence of statistically significant patterns in the spatial series of transcriptional activity. These patterns could be classified into three categories: short-range, of up to 16 kilobases (kb); medium-range, over 100-125 kb; and long-range, over 600-800 kb. We show that the significant similarities in gene activities extend beyond the length of an operon and that local patterns of coexpression are dependent on DNA supercoiling. Unlike short-range patterns, the formation of medium and long-range transcriptional patterns does not strictly depend on the level of DNA supercoiling. The long-range patterns appear to correlate with the patterns of distribution of DNA gyrase on the bacterial chromosome. CONCLUSIONS: Localization of structural components in the transcriptional signal revealed an asymmetry in the distribution of transcriptional patterns along the bacterial chromosome. The demonstration that spatial patterns of transcription could be modulated pharmacologically and genetically, along with the identification of molecular correlates of transcriptional patterns, offer for the first time strong evidence of physiologically determined higher-order organization of transcription in the bacterial chromosome

Potassium-competitive Acid Blockers: A New Therapeutic Strategy for Helicobacter pylori Eradication

The escalating prevalence of clarithromycin resistance in cases of Helicobacter pylori, insufficient acid suppression, and pharmacodynamic variations secondary to inter-individual differences in CYP2C19 polymorphism collectively contribute to suboptimal eradication rates observed with proton pump inhibitor (PPI)-based therapy. Compared with PPIs, potassium-competitive acid blockers (PCABs) produce rapid, potent, and long-lasting suppression of gastric acid through reversible inhibition of gastric H+, K+-ATPase. PCAB-based therapy results in significant inhibition of acid secretion and has therefore emerged as a novel and effective approach for H. pylori eradication. In this study, we review the efficacy and safety profile of PCAB-based eradication regimens comprising vonoprazan, tegoprazan, and fexuprazan

Retrospective Analysis of Peripheral Blood Stem Cell Transplantation for the Treatment of High-Risk Neuroblastoma

Disease relapse after autologous peripheral blood stem cell transplantation (APBSCT) is the main cause of treatment failure in high-risk neuroblastoma (NBL). To reduce relapse, various efforts have been made such as CD34+ selection and double APBSCT. Here the authors reviewed the clinical features and outcomes of high-risk NBL patients and analyzed their survival. The medical records of 36 patients with stage III or IV NBL who underwent APBSCT at Seoul National University Children's Hospital between May 1996 and May 2004 were reviewed. Total 46 APBSCTs were performed in 36 patients. Disease free survival (DFS) and overall survival of all patients were 47.7% and 68.8%, respectively. The patients were allocated to three groups according to the APBSCT type. The DFS of CD34+ non-selected single APBSCT patients (N=13), CD34+ selected single APBSCT patients (N=14), and CD34+ selected double APBSCT patients (N=9) were 55.6%, 40.6%, and 50.0%, respectively, which were not significantly different. Thus the survival was not found to be affected by CD34+ selection or transplantation number. To improve long-term survival, various efforts should be made such as chemotherapy dose intensification, more effective tumor purging, and control of minimal residual disease via the use of differentiating and immune-modulating agents

Ultrasound features of secondary appendicitis in pediatric patients

Purpose The purpose of this study was to evaluate the ultrasonographic findings of secondary appendicitis (SA) and to discuss the differential findings compared with primary appendicitis. Methods In this study, we analyzed the ultrasonographic findings of 94 patients under 15 years old of age treated at our institution from May 2005 to May 2014 who had bowel inflammation and an inflamed appendix with a maximal outer diameter >6 mm that improved with nonsurgical treatment (the SA group). Ninety-nine patients with pathologically proven acute appendicitis (the primary appendicitis [PA] group) from June 2013 to May 2014 and 44 patients with pathologically negative appendectomy results from May 2005 to May 2014 were also included to compare the ultrasonographic features of these conditions. A retrospective review of the ultrasonographic findings was performed by two radiologists. The clinical and laboratory findings were also reviewed. The results were statically analyzed using analysis of variance, the Pearson chi-square test, and the two-tailed Fisher exact test. Results Compared with PA, cases of SA had a smaller diameter (9.8 mm vs. 6.6 mm, P<0.001), and were less likely to show periappendiceal fat inflammation (98% vs. 6%, P<0.001) or an appendicolith (34% vs. 11%, P<0.001). SA showed mural hyperemia on color Doppler ultrasonography as frequently as PA (P=0.887). Conclusion The ultrasonographic features of SA included an increased diameter compared to a healthy appendix and the same level of hyperemia as in PA. However, the diameter was commonly in the equivocal range (mean diameter, 6.6 mm), and periappendiceal fat inflammation was rarely present in SA

Down-regulation of phosphoglucomutase 3 mediates sulforaphane-induced cell death in LNCaP prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables that exerts anti-oxidant, anti-inflammatory, anti-cancer and radio-sensitizing activities. Nonetheless, the mechanism responsible for SFN-induced cell death is not fully understood. In the present study, anti-cancer mechanism of SFN was elucidated in LNCaP prostate cancer cells.</p> <p>Results</p> <p>SFN exerted cytotoxicity and increased TUNEL positive cells in a concentration-dependent manner in LNCaP cells. Proteomics study revealed that levels of nine proteins including tubulin β-2, phosphoglucomutase-3 (PGM3), melanoma-derived leucine zipper containing extra-nuclear factor, activin A type I receptor precursor, smoothelin-A, KIA0073, hypothetical protein LOC57691 and two unnamed proteins were changed over 8 folds in SFN treated LNCaP cells compared to untreated control. We have further confirmed that SFN reduced PGM3 expression with western blotting and showed that PGM3 siRNA enhanced cytotoxicity demonstrated by cell morphology and TUNEL assays in LNCaP cells.</p> <p>Conclusion</p> <p>Taken together, these findings suggest that PGM3 plays a role in mediating SFN-induced cell death in LNCaP cells, and is a potential molecular therapeutic target for prostate cancer.</p

Cyr61 Expression is associated with prognosis in patients with colorectal cancer

BACKGROUND: Cysteine-rich 61 (Cyr61), a member of the CCN protein family, possesses diverse functionality in cellular processes such as adhesion, migration, proliferation, and survival. Cyr61 can also function as an oncogene or a tumour suppressor, depending on the origin of the cancer. Only a few studies have reported Cyr61 expression in colorectal cancer. In this study, we assessed the Cyr61 expression in 251 colorectal cancers with clinical follow up. METHODS: We examined Cyr61 expression in 6 colorectal cancer cell lines (HT29, Colo205, Lovo, HCT116, SW480, SW620) and 20 sets of paired normal and colorectal cancer tissues by western blot. To validate the association of Cyr61 expression with clinicopathological parameters, we assessed Cyr61 expression using tissue microarray analysis of primary colorectal cancer by immunohistochemical analysis. RESULTS: We verified that all of the cancer cell lines expressed Cyr61; 2 cell lines (HT29 and Colo205) demonstrated Cyr61 expression to a slight extent, while 4 cell lines (Lovo, HCT116, SW480, SW620) demonstrated greater Cyr61 expression than HT29 and Colo205 cell lines. Among the 20 cases of paired normal and tumour tissues, greater Cyr61 expression was observed in 16 (80%) tumour tissues than in normal tissues. Furthermore, 157 out of 251 cases (62.5%) of colorectal cancer examined in this study displayed strong Cyr61 expression. Cyr61 expression was found to be associated with pN (p = 0.018). Moreover, Cyr61 expression was associated with statistically significant cancer-specific mortality (p = 0.029). The duration of survival was significantly lesser in patients with Cyr61 high expression than in patients with Cyr61 low expression (p = 0.001). These results suggest that Cyr61 expression plays several important roles in carcinogenesis and may also be a good prognostic marker for colorectal cancer. CONCLUSIONS: Our data confirmed that Cyr61 was expressed in colorectal cancers and the expression was correlated with worse prognosis of colorectal cancers

Phenotyping of rice in salt stress environment using high-throughput infrared imaging

Phenotyping of rice (Oryza sativa L. cv. Donggin) in salt stress environment using infrared imaging was conducted. Results were correlated with the most frequently used physiological parameters such as stomatal conductance, relative water content and photosynthetic parameters. It was observed that stomatal conductance (R2 = –0.618) and relative water content (R2 = –0.852) were significantly negatively correlated with average plant temperature (thermal images), while dark-adapted quantum yield (Fv/Fm, R2 = –0.325) and performance index (R2 = –0.315) were not consistent with plant temperature. Advantages of infrared thermography and utilization of this technology for the selection of stress tolerance physiotypes are discussed in detail