Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination

Human cytomegalovirus (HCMV) encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs). These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28^YFP expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAG^YFP in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28^YFP protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28^YFP is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the ΔUS28 virus (TB40/E-FLAG^YFP) generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAG^YFP (ΔUS28) displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus.     

Nutritional status and serum zinc and selenium levels in Iranian HIV infected individuals

Background  

Human immunodeficiency virus infected individuals are prone to malnutrition due to increased energy requirements, enteropathy and increased catabolism. Trace elements such as zinc and selenium have major role in maintaining a healthy immune system. This study was designed to evaluate the nutritional status of Iranian subjects who were newly diagnosed with human immunodeficiency virus infection and to compare serum level of zinc and selenium in these patients with those of the sex and aged match healthy subjects.     

An upstream region of the mouse ZP3 gene directs expression of firefly luciferase specifically to growing oocytes in transgenic mice.

The gene encoding the mouse egg primary receptor for sperm, a zona pellucida glycoprotein called ZP3, is expressed exclusively in growing oocytes within ovaries of sexually immature and mature female mice. We have constructed a transgene in which 6.5 kilobases of ZP3 gene 5'-flanking sequence is fused to the coding region of the firefly luciferase gene, and we have generated four independent lines of transgenic mice. In these animals, the transgene is expressed exclusively in ovaries. Furthermore, within ovaries, expression is confined to growing oocytes, and luciferase activity can be detected by assaying individual, isolated oocytes. The pattern of firefly luciferase expression during oocyte growth is similar to that observed in previous studies of ZP3 expression during oogenesis in mice. Observations reported here strongly suggest that cis-acting elements present in the ZP3 gene 5'-flanking region regulate oocyte-specific and, therefore, sex-specific expression of the sperm receptor gene during mouse development. They also suggest that such elements can be used to direct expression of cloned genes specifically to oocytes of transgenic mice and to evaluate the effects of such expression on various aspects of early mammalian development.     

Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized double-blind study controlled with placebo

Backgrounds/Aims: Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset.Methods: Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery.Results: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mother or in their babies. After 3 week of treatment, patients receiving ursodeoxycholic acid (mean daily) dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), In serum bilirubin (0.36±0.19 mg/dl (mean±SD) versus 0.95±0.48 in patients receiving placebo, p<0.01), in aspartate aminostransferase (52±42 IU/l vs 98±44, p<0.05) and in alanine aminotransferase (54±50 IU/l vs 229±154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3±33.7 μmol/l vs 55.0±44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery.Conclusions: Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.     

WONCA研究论文摘要汇编——基层抑郁症风险患者的连续性服务

背景目前已开展了对重性精神病患者进提供连续性服务的研究。目的探讨基层对有抑郁症风险患者提供连续性服务的水平,并与对心力衰竭患者的服务水平进行对比。方法采用抑郁症风险患者与心力衰竭患者对比的探索性研究。采用患者问卷评估服务的持续性,包含如下内容:(1)联系的服务提供者数(个人连续性);(2)诊所内服务提供者之间的合作(团队连续性)(6个项目,分数1~5分);(3)诊所外全科医师与服务提供者之间的合作(跨界连续性)(4个项目,分数1~5分)。结果大多数抑郁症风险患者在过去1年中寻遍整个服务提供界联系了几个服务提供者,曾遇到过高水平团队连续性服务及低水平跨界连续性服务。在诊所中可接触到的不同服务提供者要明显多于心力衰竭患者服务提供者(P<0.01)。抑郁症风险患者的服务提供者之间的合作更好一些,每项平均得分4.3分,心力衰竭患者得分为4.0分(P=0.03)。然而,跨界连续性服务方面正好相反:抑郁症风险患者每项平均得分3.5分,心力衰竭患者得分为4.0分(P=0.01)。结论抑郁症风险患者与心力衰竭患者之间的探索性对比显示:体验服务连续性方面的差距不大。对此还应行进一步分析。     

Remoteness and Valence of Autobiographical Memory in Depression

We examined whether major depressive disorder (MDD) is associated with a tendency to recall more remote, specific autobiographical memories, particularly in the context of positive memories. To this end, individuals with MDD (n?=?26) and healthy controls (n?=?54) completed the Autobiographical Memory Test. Consistent with the hypothesis, remoteness of specific memories in the MDD group, but not the control group, depended on valence. Compared to the control group, the MDD group recalled more remote positive events. Additionally, the MDD group’s positive specific memories were significantly more remote than their negative specific memories. Retrieving remote positive memories might impair mood regulation and maintain an individual’s negative mood and perpetuate depression.     

A coordinated approach for the assessment of molecular subgroups in pediatric ependymomas using low-cost methods

Journal of Molecular Medicine - Although ependymoma (EPN) molecular subgroups have been well established by integrated high-throughput platforms, low- and middle-income countries still need...