非酒精性脂肪肝大鼠PPARα基因表达及脂代谢和胰岛素水平的变化

目的观察非酒精性脂肪肝（NAFLD）大鼠肝组织中PPARα基因的表达,并用PPARct激动剂进行干预,探讨其与胰岛素抵抗、脂代谢紊乱的关系。方法大鼠随机分为①正常对照组、②高脂模型组、③PPARα激动剂干预组,利用高脂饮食建立大鼠非酒精性脂肪肝模型。12周后,检测大鼠血脂、肝功能、血糖、胰岛素水平及胰岛素抵抗指数;RT-PCR法分析PPARα基因的表达;观察肝脏的形态学改变。结果PPARa激动剂可降低NAFLD大鼠转氨酶、血脂水平及胰岛素抵抗指数,可促进NAFLD大鼠中PPARa基因的表达;肝脏形态学明显改善。结论PPARα激动剂能改善NAFLD大鼠脂质代谢紊乱,有明显的保肝降酶作用,具有适度的胰岛素增敏作用。PPARα及其配体在NAFLD发病机制及治疗中的进一步深入研究,将为临床防治NAFLD提供新的思路。     

SD雌性大鼠性发育早期性器官等脏器和性激素的动态变化

目的探讨正常SD雌性大鼠性成熟前不同日龄段的脏器与促黄体生成素（LH）、促卵泡素（FSH）、雌二醇（E2）等性激素的变化及其关系。方法从生产群中取出60窝密度状态一致的SD大鼠,在不同日龄随机选取雌性大鼠,检测15、25、32、40日龄时大鼠体重、主要脏器指数,子宫、卵巢组织变化和15、25、32、40、60日龄大鼠血清LH、FSH、E2水平。结果记录了SD雌性大鼠性成熟前各脏器指数和卵巢、子宫组织变化,结果显示大鼠卵巢、子宫的增长速度大于体重的增长,而其他脏器增速大都小于体重的增长。本研究还记录了血清LH、FSH、E2水平在不同日龄段的变化规律,表明血清LH、E2浓度在32日龄时出现较为明显升高。结论不同日龄大鼠脏器指数的动态变化提示大鼠性器官在性发育早期得到机体的优先发育。血清LH、E2水平在32日龄时有了明显升高,提示性腺轴功能已经激活。60日龄大鼠血清性激素水平的波动类似于动情周期的规律性变化,推测大鼠在60日龄前即已进入性成熟,这些结果将为大鼠性发育的相关研究提供重要的参考数据。     

Developing human laboratory models of smoking lapse behavior for medication screening

Use of human laboratory analogues of smoking behavior can provide an efficient, cost-effective mechanistic evaluation of a medication signal on smoking behavior, with the result of facilitating translational work in medications development. Although a number of human laboratory models exist to investigate various aspects of smoking behavior and nicotine dependence phenomena, none have yet modeled smoking lapse behavior. The first instance of smoking during a quit attempt (i.e. smoking lapse) is highly predictive of relapse and represents an important target for medications development. Focusing on an abstinence outcome is critical for medication screening as the US Food and Drug Administration approval for cessation medications is contingent on demonstrating effects on smoking abstinence. This paper outlines a three-stage process for the development of a smoking lapse model for the purpose of medication screening. The smoking lapse paradigm models two critical features of lapse behavior: the ability to resist the first cigarette and subsequent ad libitum smoking. Within the context of the model, smokers are first exposed to known precipitants of smoking relapse (e.g. nicotine deprivation, alcohol, stress), and then presented their preferred brand of cigarettes. Their ability to resist smoking is then modeled and once smokers 'give in' and decide to smoke, they participate in a tobacco self-administration session. Ongoing and completed work developing and validating these models for the purpose of medication screening is discussed.     

Simultaneous fMRI and Electrophysiology in the Rodent Brain

To examine the neural basis of the blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) signal, we have developed a rodent model in which functional MRI data and in vivo intracortical recording can be performed simultaneously. The combination of MRI and electrical recording is technically challenging because the electrodes used for recording distort the MRI images and the MRI acquisition induces noise in the electrical recording. To minimize the mutual interference of the two modalities, glass microelectrodes were used rather than metal and a noise removal algorithm was implemented for the electrophysiology data. In our studies, two microelectrodes were separately implanted in bilateral primary somatosensory cortices (SI) of the rat and fixed in place. One coronal slice covering the electrode tips was selected for functional MRI. Electrode shafts and fixation positions were not included in the image slice to avoid imaging artifacts. The removed scalp was replaced with toothpaste to reduce susceptibility mismatch and prevent Gibbs ringing artifacts in the images. The artifact structure induced in the electrical recordings by the rapidly-switching magnetic fields during image acquisition was characterized by averaging all cycles of scans for each run. The noise structure during imaging was then subtracted from original recordings. The denoised time courses were then used for further analysis in combination with the fMRI data. As an example, the simultaneous acquisition was used to determine the relationship between spontaneous fMRI BOLD signals and band-limited intracortical electrical activity. Simultaneous fMRI and electrophysiological recording in the rodent will provide a platform for many exciting applications in neuroscience in addition to elucidating the relationship between the fMRI BOLD signal and neuronal activity.Download video file.^{(95M, mp4)}     

Differences in Reporting of Violence and Deliberate Self Harm Related Injuries to Health and Police Authorities,Rawalpindi, Pakistan

Background

The aim of study was to assess differences in reporting of violence and deliberate self harm (DSH) related injuries to police and emergency department (ED) in an urban town of Pakistan.

Methods/Principal Findings

Study setting was Rawalpindi city of 1.6 million inhabitants. Incidences of violence and DSH related injuries and deaths were estimated from record linkage of police and ED data. These were then compared to reported figures in both datasets. All persons reporting violence and DSH related injury to the police station, the public hospital''s ED, or both in Rawalpindi city from July 1, 2007 to June 30, 2008 were included. In Rawalpindi city, 1 016 intentional injury victims reported to police whereas 3 012 reported to ED. Comparing violence related fatality estimates (N = 56, 95% CI: 46–64), police reported 75.0% and ED reported 42.8% of them. Comparing violence related injury estimates (N = 7 990, 95% CI: 7 322–8 565), police reported 12.1% and ED reported 33.2% of them. Comparing DSH related fatality estimates (N = 17, 95% CI: 4–30), police reported 17.7% and ED reported 47.1% of them. Comparing DSH related injury estimates (N = 809, 95% CI: 101–1 516), police reported 0.5% and ED reported 39.9% of them.

Conclusion

In Rawalpindi city, police records were more likely to be complete for violence related deaths as compared to injuries due to same mechanism. As compared to ED, police reported DSH related injuries and deaths far less than those due to other types of violence.     

Identification of virulence factors in Vibrio cholerae isolated from Iraq during the 2007-2009 outbreak

Thousands of people were infected with Vibrio cholerae during the outbreak in Iraq in 2007-2009. Vibrio cholerae was shown to be variable in its content of virulence determinants and in its antibiotic sensitivity. This study was designed to isolate and characterize clinical and environmental V.?cholerae isolates and to determine antibiotic sensitivity, enzyme and toxin production, and the presence of virulence genes. Eighty clinical and five environmental bacterial isolates were collected and diagnosed by subjecting them to microscopic, biochemical, serological, and molecular analysis. The results revealed that 55% of clinical isolates belonged to the Inaba serotype, 32.5% to the Ogawa serotypes, and 12.5% to the Non-O1 serotype. All environmental V.?cholerae isolates belonged to the Non-O1 serotype. All environmental isolates were sensitive to all examined antimicrobial agents, while all clinical isolates showed a high sensitivity (100%) to ampicillin, gentamicin, cephalothin, tetracycline, erythromycin, and ciprofloxacin, and a high resistance (97.5%) to co-trimoxazole, nalidixic acid, and chloramphenicol. It was found that all V.?cholerae (O1) isolates were resistant to the Vibrio static O129 and all Non-O1 V.?cholerae isolates were sensitive to the Vibrio static O129. All clinical and environmental isolates produced hemolysin (100%) and lecithinase (100%), while they showed various production rates of protease (90% of clinical and 60% of environmental) and lipase (50% of clinical and 20% of environmental). The ompW gene was amplified in all the clinical and environmental V.?cholerae isolates, but not in other related and nonrelated bacteria. Multiplex PCR analysis showed that the toxR gene was amplified in all clinical and environmental isolates, while ctxA, ctxB, tcpA genes were amplified only in clinical (O1) isolates. This study indicates the differences in the production of some enzymes and toxins and in the content of virulence genes between clinical and environmental isolates in Iraq during the outbreak (2007-2009).     

Harmonised Australian Reference Intervals for Serum PINP and CTX in Adults

Bone turnover markers (BTMs) are classified as either formation or resorption markers. Their concentrations in blood or urine of adults are considered to reflect the rate of bone remodelling and may be of use in the management of patients with bone disease. Major inter-method differences exist for BTMs, and harmonisation of methods is currently being pursued at an international level. Based on published data, this article describes age- and sex-specific Australian consensus reference intervals for adults for serum procollagen type I amino-terminal propeptide (s-PINP) and serum β-isomerised carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX).     

中国内蒙古缨齿藓属(紫萼藓科)1新变种——缨齿藓菱形变种

报道了内蒙古清水河黄土丘陵地区发现的紫萼藓科1新变种——缨齿藓菱形变种[Jaffueliobryum wrightii(Sull.)Thér.var.rhombicumX.L.BaiSarula],该变种与干旱山地岩面生境中的原变种缨齿藓[Jaffueliobryum wrightii(Sull.)Thér.]相似,生境的变化导致其形态发生变化,主要表现在上部细胞菱形和细胞壁背部强烈加厚,未分化的叶上部边缘细胞、中肋横切面细胞不分化,叶片长0.7~0.8mm,毛尖长0.8~1.3mm。文中对缨齿藓及其新变种的形态学特征,分布和生境进行了描述,并提供了显微照片,另外,列出了缨齿藓属5个种的检索表。     

Distinct Sets of Rab6 Effectors Contribute to ZW10‐ and COG‐Dependent Golgi Homeostasis

The organization of the Golgi apparatus is determined in part by the interaction of Rab proteins and their diverse array of effectors. Here, we used multiple approaches to identify and characterize a small subset of effectors that mimicked the effects of Rab6 on Golgi ribbon organization. In a visual‐based, candidate protein screen, we found that the individual depletion of any of three Rab6 effectors, myosin IIA (MyoIIA), Kif20A and Bicaudal D (BicD), was sufficient to suppress Golgi ribbon fragmentation/dispersal coupled to retrograde tether proteins in a manner paralleling Rab6. MyoIIA and Kif20A depletions were pathway selective and suppressed ZW10‐dependent Golgi ribbon fragmentation/dispersal only whereas BicD depletion, like Rab6, suppressed both ZW10‐ and COG‐dependent Golgi ribbon fragmentation. The MyoIIA effects could be produced in short‐term assays by the reversible myosin inhibitor, blebbistatin. At the electron microscope level, the effects of BicD‐depletion mimicked many of those of Rab6‐depletion: longer and more continuous Golgi cisternae and a pronounced accumulation of coated vesicles. Functionally, BicD‐depleted cells were inhibited in transport of newly synthesized VSV‐G protein to the cell surface. In summary, our results indicate small, partially overlapping subsets of Rab6 effectors are differentially important to two tether‐dependent pathways essential to Golgi organization and function.