Cyclin-dependent kinase 4 is a novel target in micoRNA-195-mediated cell cycle arrest in bladder cancer cells

AbstractmiRNAs are a class of small-noncoding RNAs capable of negatively regulating gene expression. Here, we found that miR-195 is down-regulated in human bladder cancer tissue versus normal adjacent tissue. To better characterize the role of miR-195 in bladder cancer, we conducted gain of function analysis by transfecting bladder cancer cell line T24 with chemically synthesized miR-195 mimic. We identified CDK4, an early G1 cell cycle regulator, as a novel target of miR-195. Selective over-expression of miR-195 could induce G1-phase arrest in T24 cells, and subsequently inhibit T24 cell growth. These findings indicate that miR-195 could be a potential tumor suppressor in bladder cancer

Applicability of Interpretation II concerning the Insurance Law to the Limitation of Action with Regard to Subrogation Rights in Marine Insurance

杨运福，广东恒福律师事务所主任、执行和高级合伙人，海事律师，仲裁员，法律硕士。 吴星奎，广东恒福律师事务所副主任、合伙人，海事律师，法学硕士。【中文摘要】《最高人民法院关于适用若干问题的解释(二)》(以下简称“《保险司法解释(二)》”)第16条规定：保险人代位求偿权的诉讼时效期间应自其取得代位求偿权之日起算。目前，对于上述规定是否可以适用于海上保险代位求偿权，即保险人就货物运输保险合同对承运人的诉讼时效，是按照上述司法解释的规定从其取得代位求偿权开始计算，还是从被保险人对承运人诉讼时效的起算点即从承运人交付或者应当交付货物之日起算，海事司法实践和理论上存在很大的争议。笔者认为 ,《保险法司法解释(二)》的规定并不能适用于海上货物运输保险代位诉讼中诉讼时效的起算。 【Abstract】Article 16 of Interpretation II of the Supreme People's Court on Several Issues concerning the Application of the Insurance Law of the People's Republic of China (hereinafter “Interpretation II”) provides for the following: the time limitation for an insurer's subrogation right shall be calculated from the date when it acquires such a right. Currently, maritime jurisprudents and juridical practitioners are embroiled in controversy over the question of whether this provision may be applied to subrogation rights in marine insurance. That is, should the limitation of action by the insurer against the carrier based on the cargo transportation insurance contract start from the date when the insurer acquired its subrogation right, as stipulated in the juridical interpretation above, or from the day on which the goods were delivered or should have been delivered by the carrier (the starting time of limitation of action by the insured against the carrier)? The authors assert that the provisions of Interpretation II do not apply to the calculation of time limitation of subrogation claims for insurers in respect to carriage of goods by sea

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

Explosive growth in the study of microbial epigenetics has revealed a diversity of chemical structures and biological functions of DNA modifications in restriction-modification (R-M) and basic genetic processes. Here, we describe the discovery of shared consensus sequences for two seemingly unrelated DNA modification systems, [superscript 6m]A methylation and phosphorothioation (PT), in which sulfur replaces a nonbridging oxygen in the DNA backbone. Mass spectrometric analysis of DNA from Escherichia coli B7A and Salmonella enterica serovar Cerro 87, strains possessing PT-based R-M genes, revealed d(G[subscript PS] [superscript 6m]A) dinucleotides in the G[subscript PS] [superscript 6m]AAC consensus representing ∼5% of the 1,100 to 1,300 PT-modified d(G[subscript PS] A) motifs per genome, with [superscript 6m]A arising from a yet-to-be-identified methyltransferase. To further explore PT and 6m A in another consensus sequence, G[subscript PS] [superscript 6m]ATC, we engineered a strain of E. coli HST04 to express Dnd genes from Hahella chejuensis KCTC2396 (PT in G[subscript PS] ATC) and Dam methyltransferase from E. coli DH10B ( [superscript 6m] A in G [superscript 6m] ATC). Based on this model, in vitro studies revealed reduced Dam activity in G PS ATC-containing oligonucleotides whereas single-molecule real-time sequencing of HST04 DNA revealed [superscript 6m] A in all 2,058 G[subscript PS] ATC sites (5% of 37,698 total GATC sites). This model system also revealed temperature-sensitive restriction by DndFGH in KCTC2396 and B7A, which was exploited to discover that [superscript 6m] A can substitute for PT to confer resistance to restriction by the DndFGH system. These results point to complex but unappreciated interactions between DNA modification systems and raise the possibility of coevolution of interacting systems to facilitate the function of each

Understanding the Physiological Role of Electroneutral Na+-Coupled HCO3− Cotransporter and Its Therapeutic Implications

Acid–base homeostasis is critical for proper physiological function and pathology. The SLC4 family of HCO3− transmembrane cotransporters is one of the HCO3− transmembrane transport carriers responsible for cellular pH regulation and the uptake or secretion of HCO3− in epithelial cells. NBCn1 (SLC4A7), an electroneutral Na+/HCO3− cotransporter, is extensively expressed in several tissues and functions as a cotransporter for net acid extrusion after cellular acidification. However, the expression and activity level of NBCn1 remain elusive. In addition, NBCn1 has been involved in numerous other cellular processes such as cell volume, cell death/survival balance, transepithelial transport, as well as regulation of cell viability. This review aims to give an inclusive overview of the most recent advances in the research of NBCn1, emphasizing the basic features, regulation, and tissue-specific physiology as well as the development and application of potent inhibitors of NBCn1 transporter in cancer therapy. Research and development of targeted therapies should be carried out for NBCn1 and its associated pathways

The Development and Application of Numerical Packages Based on NetSolve

Abstract. NetSolve is a kind of grid middleware used for high performance compute. In this article, the architecture and operational principle of NetSolve are first analyzed. This paper mainly discusses the implementation of the server with several numerical packages and numerical experiment is given. At last, we point out the limitations of the Netsolve.

The Chronic and Short-Term Effects of Gefinitib on Airway Remodeling and Inflammation in a Mouse Model of Asthma

Background: Asthma is a complex and heterogeneous chronic inflammatory disorder which is characterized by airway remodeling and airway inflammation, including goblet cell and airway smooth muscle cell hyperplasia, mucus hypersecretion and eosinophils infiltration. Epidermal growth factor receptor (EGFR) plays an important role in goblet cell hyperplasia and mucus hypersecretion. We aimed to investigate the effects of gefitinib, an EGFR inhibitor, on ovalbumin (OVA)-induced airway remodeling and inflammation of a mouse model of asthma. Methods: Pathological changes of OVA sensitization of BALB/c mice were measured by H&E and PAS staining; pEGFR, Bcl-2 and Bax expression was measured by western blot; ELISA was used to measure the level of muc5ac, IL-13 and IFN-γ; TUNEL staining was used to detect goblet cell apoptosis. Results: At the present study, H&E and PAS staining showed that mice pretreated with gefinitib developed fewer pathological changes compared with asthmatic mice and gefinitib treatment asthmatic mice, such as a remarkable reduction in airway inflammation, goblet cell and airway smooth muscle cell hyperplasia. Chronic gefitinib treatment or short-term gefitinib treatment significant down-regulate the expression of pEGFR compared with asthma group. Also, chronic gefitinib treatment markedly decreased the levels of muc5ac and IL-13 in BALF, whereas the level of IFN-γ did not change obviously. TUNEL staining showed that the goblet cell apoptosis rate was much higher in the short-term gefinitib treatment group compared with the asthma and chronic gefitinib treatment group which was accompanied by a decrease in Bcl-2 levels and an increase in Bax expression in goblet cells. Conclusion: In summary, our results suggested that gefinitib may have a potential role in airway remodeling and inflammation, and may be an effective pharmacotherapy for asthma

Correction: Bacterial community and arsenic functional genes diversity in arsenic contaminated soils from different geographic locations.

[This corrects the article DOI: 10.1371/journal.pone.0176696.]