Genome Sequence of a Nicotine-Degrading Strain of Arthrobacter

We announce a 4.63-Mb genome assembly of an isolated bacterium that is the first sequenced nicotine-degrading Arthrobacter strain. Nicotine catabolism genes of the nicotine-degrading plasmid pAO1 were predicted, but plasmid function genes were not found. These results will help to better illustrate the molecular mechanism of nicotine degradation by Arthrobacter.     

非药物治疗极低出生体重儿喂养不耐受的临床观察

目的:将非药物性干预措施与传统药物方法治疗极低出生体重儿喂养不耐受的临床疗效进行观察比较。方法:选取哈尔滨医科大学附属第二医院2011年1月至2013年4月出生的喂养不耐受极低出生体重儿110例。按入院顺序随机分为药物治疗组(MED)55例、非药物治疗组(NON-MED)55例。药物治疗组采用红霉素;非药物治疗组采用腹部按摩法与非营养性吸吮。结果:两组患儿经治疗后,MED组腹胀消失天数(4.4±0.5)、呕吐天数(2.2±0.5)、每日呕吐次数(3.5±0.8)、胃潴留量占每日喂养量(18.3±0.8)、达全肠道喂养天数(8.2±0.7);NON-MED组腹胀消失天数(3.7±0.1)、呕吐天数(1.9±0.6)、每日呕吐次数(2.8±0.1)、胃潴留量占每日喂养量(12.6±0.4)、达全肠道喂养天数(6.1±0.3)。各项治疗指标的对比中,差异均有统计学意义(P0.05)。MED组治疗有效率76.4%;NON-MED组治疗有效率83.6%。结论:非药物性干预措施可有效改善极低出生体重儿喂养不耐受。     

Effect of a Low-Protein Diet Supplemented with Ketoacids on Skeletal Muscle Atrophy and Autophagy in Rats with Type 2 Diabetic Nephropathy

A low-protein diet supplemented with ketoacids maintains nutritional status in patients with diabetic nephropathy. The activation of autophagy has been shown in the skeletal muscle of diabetic and uremic rats. This study aimed to determine whether a low-protein diet supplemented with ketoacids improves muscle atrophy and decreases the increased autophagy observed in rats with type 2 diabetic nephropathy. In this study, 24-week-old Goto-Kakizaki male rats were randomly divided into groups that received either a normal protein diet (NPD group), a low-protein diet (LPD group) or a low-protein diet supplemented with ketoacids (LPD+KA group) for 24 weeks. Age- and weight-matched Wistar rats served as control animals and received a normal protein diet (control group). We found that protein restriction attenuated proteinuria and decreased blood urea nitrogen and serum creatinine levels. Compared with the NPD and LPD groups, the LPD+KA group showed a delay in body weight loss, an attenuation in soleus muscle mass loss and a decrease of the mean cross-sectional area of soleus muscle fibers. The mRNA and protein expression of autophagy-related genes, such as Beclin-1, LC3B, Bnip3, p62 and Cathepsin L, were increased in the soleus muscle of GK rats fed with NPD compared to Wistar rats. Importantly, LPD resulted in a slight reduction in the expression of autophagy-related genes; however, these differences were not statistically significant. In addition, LPD+KA abolished the upregulation of autophagy-related gene expression. Furthermore, the activation of autophagy in the NPD and LPD groups was confirmed by the appearance of autophagosomes or autolysosomes using electron microscopy, when compared with the Control and LPD+KA groups. Our results showed that LPD+KA abolished the activation of autophagy in skeletal muscle and decreased muscle loss in rats with type 2 diabetic nephropathy.     

A Novel Method for Fast Change-Point Detection on Simulated Time Series and Electrocardiogram Data

Although Kolmogorov-Smirnov (KS) statistic is a widely used method, some weaknesses exist in investigating abrupt Change Point (CP) problems, e.g. it is time-consuming and invalid sometimes. To detect abrupt change from time series fast, a novel method is proposed based on Haar Wavelet (HW) and KS statistic (HWKS). First, the two Binary Search Trees (BSTs), termed TcA and TcD, are constructed by multi-level HW from a diagnosed time series; the framework of HWKS method is implemented by introducing a modified KS statistic and two search rules based on the two BSTs; and then fast CP detection is implemented by two HWKS-based algorithms. Second, the performance of HWKS is evaluated by simulated time series dataset. The simulations show that HWKS is faster, more sensitive and efficient than KS, HW, and T methods. Last, HWKS is applied to analyze the electrocardiogram (ECG) time series, the experiment results show that the proposed method can find abrupt change from ECG segment with maximal data fluctuation more quickly and efficiently, and it is very helpful to inspect and diagnose the different state of health from a patient''s ECG signal.     

Exogenous H2S prevents the nuclear translocation of PDC-E1 and inhibits vascular smooth muscle cell proliferation in the diabetic state

Hydrogen sulphide (H₂S) inhibits vascular smooth muscle cell (VSMC) proliferation induced by hyperglycaemia and hyperlipidaemia; however, the mechanisms are unclear. Here, we observed lower H₂S levels and higher expression of the proliferation-related proteins PCNA and cyclin D1 in db/db mouse aortae and vascular smooth muscle cells treated with 40 mmol/L glucose and 500 μmol/L palmitate, whereas exogenous H₂S decreased PCNA and cyclin D1 expression. The nuclear translocation of mitochondrial pyruvate dehydrogenase complex-E1 (PDC-E1) was significantly increased in VSMCs treated with high glucose and palmitate, and it increased the level of acetyl-CoA and histone acetylation (H3K9Ac). Exogenous H₂S inhibited PDC-E1 translocation from the mitochondria to the nucleus because PDC-E1 was modified by S-sulfhydration. In addition, PDC-E1 was mutated at Cys101. Overexpression of PDC-E1 mutated at Cys101 increased histone acetylation (H3K9Ac) and VSMC proliferation. Based on these findings, H₂S regulated PDC-E1 S-sulfhydration at Cys101 to prevent its translocation from the mitochondria to the nucleus and to inhibit VSMC proliferation under diabetic conditions.     

Suppression of Viral RNA Binding and the Assembly of Infectious Hepatitis C Virus Particles In Vitro by Cyclophilin Inhibitors

Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable component of the HCV replication and assembly machineries. Although its precise mechanism of action is not yet clear, current evidence indicates that its structure and function are regulated by the cellular peptidylprolyl isomerase cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of NS5A, in a distributed fashion, and modulates the structure of the disordered domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA) and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in addition to their well-documented inhibitory effect on RNA replication. Although the interaction between NS5A and other viral proteins is not affected by CPIs, RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is significantly inhibited by CPI treatment, and sensitivity of RNA binding is correlated with previously characterized CyPA dependence or CsA sensitivity of HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic and a full-length replicon of JFH-1 was due, at least in part, to an additional role that CyPA plays in HCV assembly, a conclusion that is supported by experiments with the clinical CPI alisporivir. The host-directed nature and the ability to interfere with more than one step in the HCV life cycle may result in a higher genetic barrier to resistance for this class of HCV inhibitors.