Roles of CytR,an anti-activator of cyclic-AMP receptor protein (CRP) on flagellar expression and virulence in uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is a major pathogen that causes urinary tract infection (UTI), a common bacterial infectious disease. This bacterium invades the urinary tract cells, where it aggregates, and subsequently forms multicellular colonies termed intracellular bacterial communities (IBCs). The motility of the bacteria plays a key role in the mechanism of virulence in the host bladder. Here, we show that CytR is a modulator of bacterial internalization and aggregation within the bladder epithelial cells sustained by CRP in UPEC. Mutational analyses and gel-shift assays indicated that CytR represses the expression of flhD, thereby encoding a master regulator for flagellar expression that is responsible for bacterial motility when CRP is present, whereas CRP is an activator of flhD expression. Thus, elevated flagellar expression was involved in promoted virulence in the cytR mutant. These combined observations suggest another regulatory layer of flagellar expression and the role of CytR in UPEC virulence.     

Dependence of Subjective Traverse Length on Velocity of Moving Tactile Stimuli

Two series of experiments were performed to assess the effects of stimulus velocity on human subjects' perception of the distance traversed by a moving tactile stimulus. In all experiments, constant-velocity stimuli were applied to the dorsal surface of the left forearm; velocities ranging between 1.0 and 256 cm/sec were used. In some experiments the stimuli moved from distal to proximal over the skin, and in others they moved from proximal to distal. The length of skin contacted by the moving stimulus was defined by a plate having an aperture of 4.0 × 0.5 cm.

In the first series of experiments, subjects were required to compare the distance traversed by a test stimulus delivered 2 sec after a standard stimulus, and also to report the on-locus and the off-locus of the brushing stimulus. In the second series of experiments, the subjects rated the perceived distance on the skin using a free-magnitude-estimation procedure. The data from both series of experiments defined the same relationship between stimulus velocity and perceived stimulus distance. More specifically, although the length of skin contacted by the stimulus was the same at all velocities, subjects' estimates of stimulus distance decreased with increasing stimulus velocity. In addition, the function relating estimates of stimulus distance to velocity was flat for velocities between 5 and 20 cm/sec, but possessed an appreciable negative slope at lower and higher velocities.

It is interesting that the plateau of the relationship between perceived stimulus distance and velocity occurred within the range of velocities that human subjects employ to scan textured surfaces; it also corresponded precisely with the range of stimulus velocities at which the directional sensitivity of somatosensory cortical neurons and human subjects is optimal.     

Anatomical location of the medial lemniscus and spinothalamic tract at the pons in the human brain: A diffusion tensor tractography study

Abstract

Using diffusion tensor tractography, we investigated the anatomical location of medial lemniscus (ML) and spinothalamic tract (STT) at pons. We recruited 47 healthy volunteers. Evaluation of the anatomical location of ML and STT was performed using the highest probabilistic location at the upper, middle, and lower pons. According to findings, MLs were located around the middle to medial one-third, between midline and lateral boundary of pons in the pontine tegmentum and STTs were located posterolaterally to ML.     

A change in the pattern in circadian running‐wheel activity after lesions of the intergeniculate leaflet and ventral lateral geniculate nucleus in the Syrian hamster

Abstract

The suprachiasmatic nuclei (SCN) contain the endogenous mammalian circadian pacemaker, which generates the circadian rhythm in locomotor activity. In Syrian hamsters with free‐running rhythms, the onset of running‐wheel activity is very precise and predictable while the end (offset) is more variable. From the thalamic intergeniculate leaflet (IGL) and the ventral lateral geniculate nucleus (vLGN) a projection to the SCN originates. Animals with a lesion aimed at the IGL/vLGN and sham‐and unoperated controls were kept in continuous darkness. With linear regression, lines were fitted through 10 successive onsets and offsets of activity and the mean deviation of the onsets and offsets from the fitted lines was determined. Animals with a complete or partial lesion of the IGL/vLGN had a smaller mean deviation of the circadian activity offset from the fitted regression line (0.313 h) compared with the grouped control animals (0.678 h). To test the difference statistically, we compared the sum of the square residuals of the circadian offsets between the groups. This difference was highly significant (F(69,64)=4.16, p<0.0001), which indicates that animals with a lesion of the IGL/ vLGN have a less variable circadian offset of running‐wheel activity. No differences were observed in the variability in the circadian onset of locomotor activity between experimental and control animals. It is concluded that the IGL/vLGN influence the variability of the offset of the circadian running‐wheel activity.     

Transcription of the human microsomal epoxide hydrolase gene (EPHX1) is regulated by an HNF-4α/CAR/RXR/PSF complex

Microsomal epoxide hydrolase (mEH) is a bifunctional protein that plays a central role in the metabolism of numerous xenobiotics as well as mediating the sodium-dependent transport of bile acids into hepatocytes where they are involved in cholesterol excretion and metabolism, lipid digestion and regulating numerous signaling pathways. Previous studies have demonstrated the critical role of GATA-4 and a C/EBPα–NF/Y complex in the regulation of the mEH gene (EPHX1). In this study we show that HNF-4α and CAR/RXR also bind to the proximal promoter region and regulate EPHX1 expression. Bile acids, which inhibit the expression of HNF-4α also decrease the expression of EPHX1. Studies also established that the binding of HNF-4α was essential for the activation of EPHX1 activity by CAR suggesting the formation of a complex between these adjacent factors. The nature of this regulatory complex was further explored using a biotinylated oligonucleotide of this region in conjunction with BioMag beads and mass spectrometric analysis which demonstrated the presence of an additional inhibitory factor (PSF), confirmed by co-immunoprecipitation and ChIP analyses, which interacted with DNA-bound CAR/RXR/HNF-4α forming a 4-component regulatory complex.     

血清PCT联合痰培养检测在呼吸道感染疾病中的应用

目的:研究血清降钙素原(PCT)联合痰培养检测在呼吸道感染疾病中的应用价值。方法:选择2012年1月至2014年12月在我院接受治疗的呼吸道感染患者100例进行研究。分析痰培养菌群的分布情况以及PCT的检测结果,对比痰培养细菌感染者及真菌感染者的菌种分类及PCT检测结果。结果:检出病原菌的患者PCT水平均分别显著高于正常菌群及未见细菌生长的患者,差异均有统计学意义(均P0.05)。细菌感染PCT阳性比例与真菌感染相比,差异无统计学意义(P0.05)。细菌感染中,革兰氏阳性菌的PCT水平(0.74±0.33μg/L)与革兰氏阴性菌(0.72±0.24μg/L)对比,差异无统计学意义(P0.05)。真菌感染中,白假丝酵母菌及烟曲霉菌的PCT阳性比例最高,分别为60.00%及80.00%。结论:血清PCT与痰培养检测应用于评价有呼吸道感染的患者病情,具有一定的反馈意义,但无法确定患者的呼吸道感染究竟是细菌感染亦或是真菌感染。     

Spatial separation of replisome arrest sites influences homologous recombination quality at a Tus/Ter-mediated replication fork barrier

The Escherichia coli replication fork arrest complex Tus/Ter mediates site-specific replication fork arrest and homologous recombination (HR) on a mammalian chromosome, inducing both conservative “short tract” gene conversion (STGC) and error-prone “long tract” gene conversion (LTGC) products. We showed previously that bidirectional fork arrest is required for the generation of STGC products at Tus/Ter-stalled replication forks and that the HR mediators BRCA1, BRCA2 and Rad51 mediate STGC but suppress LTGC at Tus/Ter-arrested forks. Here, we report the impact of Ter array length on Tus/Ter-induced HR, comparing HR reporters containing arrays of 6, 9, 15 or 21 Ter sites—each targeted to the ROSA26 locus of mouse embryonic stem (ES) cells. Increasing Ter copy number within the array beyond 6 did not affect the magnitude of Tus/Ter-induced HR but biased HR in favor of LTGC. A “lock”-defective Tus mutant, F140A, known to exhibit higher affinity than wild type (wt)Tus for duplex Ter, reproduced these effects. In contrast, increasing Ter copy number within the array reduced HR induced by the I-SceI homing endonuclease, but produced no consistent bias toward LTGC. Thus, the mechanisms governing HR at Tus/Ter-arrested replication forks are distinct from those governing HR at an enzyme-induced chromosomal double strand break (DSB). We propose that increased spatial separation of the 2 arrested forks encountering an extended Tus/Ter barrier impairs the coordination of DNA ends generated by the processing of the stalled forks, thereby favoring aberrant LTGC over conservative STGC.     

绍兴地区2型糖尿病尿路感染病原菌及其耐药性分析

摘要：目的 回顾分析本院2型糖尿病伴尿路感染患者的病原菌分布特点及其耐药性,为指导临床用药提供参考。方法 收集2013年1月至2014年1月2型糖尿病合并尿路感染患者186例,留取中段尿分离培养病原菌,用VITEK-2细菌鉴定仪鉴定,纸片扩散法（K-B）测定药物敏感性。结果 186例患者中段尿共培养出病原菌137株,其中革兰阴性菌102株（74.45%）,革兰阳性菌21株（15.33%）,真菌14株（10.22%）。革兰阴性菌以大肠埃希菌为主,检出79株占57.66%,对青霉素类,头孢菌素类,喹诺酮类抗菌药耐药率较高均＞50.00%,对头霉素类药物如头孢替坦、含酶抑制剂复合物如哌拉西林/他唑巴坦以及碳青霉烯类药物敏感率均达100.00%;革兰阳性球菌以无乳链球菌为主,检出10株占7.30%,对克林霉素及红霉素耐药率较高,耐药率＞50.00%,而对氯霉素、呋喃妥因、利奈唑烷、替加环素、万古霉素敏感率均达100.00%。除1株光滑假丝酵母菌对氟康唑和伊曲康唑中介,其余13株真菌对两性霉素B、5-氟胞嘧啶、伏立康唑、氟康唑、伊曲康唑这5种抗真菌药物均敏感。结论 2型糖尿病患者发生尿路感染的病原菌以大肠埃希菌为主,且有较高的耐药率。