天山马鹿南山种群肠道寄生虫的流行病学调查

为了解野生天山马鹿胃肠道寄生虫感染情况,2011 年10 月至2012 年6 月和2012 年9 月,利用漂浮法和沉淀法,对分布于新疆乌鲁木齐南山山区天山马鹿的306 份马鹿粪便进行了调查。结果表明,天山马鹿寄生虫感染情况较为严重,主要有鞭虫卵、蛔虫卵、球虫卵、线虫卵和幼虫,总感染率高达85. 6% 。其中鞭虫卵、蛔虫卵、球虫卵及其他(未能鉴定分类的线虫卵和幼虫)的平均感染率分别为78.1% 、56. 9% 、0.7% 和25. 8% ,感染强度(EPG)分别为106.4、8. 6、0.9 和3.9,其中鞭虫卵占优势。混合感染情况比较严重,鞭虫卵和蛔虫卵的混合感染率为最高,可达44% 。     

Statin-induced inhibition of HIV-1 release from latently infected U1 cells reveals a critical role for protein prenylation in HIV-1 replication.

Latent infection of human immunodeficiency virus type 1 (HIV-1) represents a major hurdle in the treatment of acquired immunodeficiency syndrome (AIDS) patients. Statins were recently reported to suppress acute HIV-1 infection and reduce infectious virion production, but the precise mechanism of inhibition has remained elusive. Here we demonstrate that lypophilic statins suppress HIV-1 virion release from tumor necrosis factor alpha-stimulated latently infected U1 cells through inhibition of protein geranylgeranylation, but not by cholesterol depletion. Indeed, this suppression was reversed by the addition of geranylgeranylpyrophosphate, and a geranylgeranyltransferase-1 inhibitor reduced HIV-1 production. Notably, silencing of the endogenous Rab11a GTPase expression in U1 cells by RNA interference destabilized Gag and reduced virion production both in vitro and in NOD/SCID/gammac null mice. Our findings thus suggest that small GTPase proteins play an important role in HIV-1 replication, and therefore could be attractive molecular targets for anti-HIV-1 therapy.     

Primary Human Leukocyte Subsets Differentially Express Vaccinia Virus Receptors Enriched in Lipid Rafts

Poxviruses, including vaccinia virus (VV) and canarypox virus (ALVAC), do not indiscriminately infect all cell types of the primary human leukocytes (PHLs) that they encounter but instead demonstrate an extremely strong bias toward infection of monocytes and monocyte lineage cells. We studied the specific molecular events that determine the VV tropism for major PHL subsets including monocytes, B cells, neutrophils, NK cells, and T cells. We found that VV exhibited an extremely strong bias of cell surface protein-dependent binding to monocytes, B cells, and activated T cells to a similar degree and to neutrophils to a much lesser extent. Resting T cells and resting NK cells exhibited only trace amounts of VV binding. Activated T cells, however, became permissive to VV binding, infection, and replication, while activated NK cells still resisted VV binding. VV binding strongly colocalized with lipid rafts on the surfaces of all VV binding-susceptible PHL subsets, even when lipid rafts were relocated to cell uropods upon cell polarization. Immunosera raised against detergent-resistant membranes (DRMs) from monocytes or activated T cells, but not resting T cells, effectively cross-blocked VV binding to and infection of PHL subsets. CD29 and CD98, two lipid raft-associated membrane proteins that had been found to be important for VV entry into HeLa cells, had no effect on VV binding to and infection of primary activated T cells. Our data indicate that PHL subsets express VV protein receptors enriched in lipid rafts and that receptors are cross-presented on all susceptible PHLs.     

Direct effects of HIV-1 Tat on excitability and survival of primary dorsal root ganglion neurons: possible contribution to HIV-1-associated pain

The vast majority of people living with human immunodeficiency virus type 1 (HIV-1) have pain syndrome, which has a significant impact on their quality of life. The underlying causes of HIV-1-associated pain are not likely attributable to direct viral infection of the nervous system due to the lack of evidence of neuronal infection by HIV-1. However, HIV-1 proteins are possibly involved as they have been implicated in neuronal damage and death. The current study assesses the direct effects of HIV-1 Tat, one of potent neurotoxic viral proteins released from HIV-1-infected cells, on the excitability and survival of rat primary dorsal root ganglion (DRG) neurons. We demonstrated that HIV-1 Tat triggered rapid and sustained enhancement of the excitability of small-diameter rat primary DRG neurons, which was accompanied by marked reductions in the rheobase and resting membrane potential (RMP), and an increase in the resistance at threshold (R(Th)). Such Tat-induced DRG hyperexcitability may be a consequence of the inhibition of cyclin-dependent kinase 5 (Cdk5) activity. Tat rapidly inhibited Cdk5 kinase activity and mRNA production, and roscovitine, a well-known Cdk5 inhibitor, induced a very similar pattern of DRG hyperexcitability. Indeed, pre-application of Tat prevented roscovitine from having additional effects on the RMP and action potentials (APs) of DRGs. However, Tat-mediated actions on the rheobase and R(Th) were accelerated by roscovitine. These results suggest that Tat-mediated changes in DRG excitability are partly facilitated by Cdk5 inhibition. In addition, Cdk5 is most abundant in DRG neurons and participates in the regulation of pain signaling. We also demonstrated that HIV-1 Tat markedly induced apoptosis of primary DRG neurons after exposure for longer than 48 h. Together, this work indicates that HIV-1 proteins are capable of producing pain signaling through direct actions on excitability and survival of sensory neurons.     

Association of Neisseria gonorrhoeae OpaCEA with Dendritic Cells Suppresses Their Ability to Elicit an HIV-1-Specific T Cell Memory Response

Infection with Neisseria gonorrhoeae (N. gonorrhoeae) can trigger an intense local inflammatory response at the site of infection, yet there is little specific immune response or development of immune memory. Gonococcal surface epitopes are known to undergo antigenic variation; however, this is unlikely to explain the weak immune response to infection since individuals can be re-infected by the same serotype. Previous studies have demonstrated that the colony opacity-associated (Opa) proteins on the N. gonorrhoeae surface can bind human carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) on CD4⁺ T cells to suppress T cell activation and proliferation. Interesting in this regard, N. gonorrhoeae infection is associated with impaired HIV-1 (human immunodeficiency virus type 1)-specific cytotoxic T-lymphocyte (CTL) responses and with transient increases in plasma viremia in HIV-1-infected patients, suggesting that N. gonorrhoeae may also subvert immune responses to co-pathogens. Since dendritic cells (DCs) are professional antigen presenting cells (APCs) that play a key role in the induction of an adaptive immune response, we investigated the effects of N. gonorrhoeae Opa proteins on human DC activation and function. While morphological changes reminiscent of DC maturation were evident upon N. gonorrhoeae infection, we observed a marked downregulation of DC maturation marker CD83 when the gonococci expressing CEACAM1-specific Opa_CEA, but not other Opa variants. Consistent with a gonococcal-induced defect in maturation, Opa_CEA binding to CEACAM1 reduced the DCs’ capacity to stimulate an allogeneic T cell proliferative response. Moreover, Opa_CEA-expressing N. gonorrhoeae showed the potential to impair DC-dependent development of specific adaptive immunity, since infection with Opa_CEA-positive gonococci suppressed the ability of DCs to stimulate HIV-1-specific memory CTL responses. These results reveal a novel mechanism to explain why infection of N. gonorrhoeae fails to trigger an effective specific immune response or develop immune memory, and may affect the potent synergy between gonorrhea and HIV-1 infection.     

Is Peri-Operative Steroid Replacement Therapy Necessary for the Pituitary Adenomas Treated with Surgery? A Systematic Review and Meta Analysis

Background

Patients with pituitary adenomas usually receive “stress dose” steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery.

Methods

We searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed.

Findings

There are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There was no significant differences of early postoperative diabetes insipidus between no supplementation patients and in supplementation patients(P=0.82). Conversely, there may be some disadvantages of high levels of cortisols such as high incidence of osteopenia and bone derangement and even the increased mortality rate. The patients with MSC levels of less than 60 nmol/l at 3 days after operation is considered as adrenal insufficient and more than 270 nmol/l as adrenal sufficient. To patients with MSC levels of 60–270 nmol/l, we need more clinical data to establish further cortisol supplementation criteria.     

Role for protein geranylgeranylation in adult T-cell leukemia cell survival

Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL.     

吐鲁番传统馕饼酸面团中微生物多样性及挥发性香气成分的分析

【目的】新疆传统发酵食品馕饼是维吾尔族的传统主食之一,在不同地区居住的维吾尔族家庭都具有不同的面团发酵方法。对吐鲁番托克逊县坎儿井饮用水制成的传统馕饼酸面团进行可培养微生物组成分析及其面团在发酵过程中挥发性香气成分分析。【方法】采用纯培养、16S r RNA基因序列分析法、26S r RNA基因D1/D2区序列分析法对发酵面团微生物多样性进行分析;采用顶空固相微萃取-气质联用法(HS-SPME-GC-MS)检测挥发性香气成分。【结果】从两种样品中共鉴定到9株旧金山乳杆菌(Lactobacillus sanfranciscensis)、4株食窦魏斯氏菌(Weissella cibaria)、11株解淀粉芽孢杆菌(Bacillus amyloliquefaciens),1株嗜热解淀粉杆菌(Bacillus shackletonii)、1株枯草芽孢杆菌(Bacillus subtills)和10株酿酒酵母菌(Saccharomyces cerevisiae),其中2号样品中未分离到任何可培养酵母菌。GC/MS检测表明,两组酸面团的主要香气成分有脂类、醇类、醛类。【结论】吐鲁番托克逊县传统馕饼酸面团中得到的优势细菌为解淀粉芽孢杆菌和旧金山乳杆菌,优势酵母菌为酿酒酵母菌。虽然2号样品中没有酵母菌,但并未影响到其多种风味物质的产生。用坎儿井水和成的面团均比自来水和成的面团(对照)产生的芳香类物质种类丰富,相对百分含量高。