RIM genes differentially contribute to organizing presynaptic release sites

Tight coupling of Ca(2+) channels to the presynaptic active zone is critical for fast synchronous neurotransmitter release. RIMs are multidomain proteins that tether Ca(2+) channels to active zones, dock and prime synaptic vesicles for release, and mediate presynaptic plasticity. Here, we use conditional knockout mice targeting all RIM isoforms expressed by the Rims1 and Rims2 genes to examine the contributions and mechanism of action of different RIMs in neurotransmitter release. We show that acute single deletions of each Rims gene decreased release and impaired vesicle priming but did not alter the extracellular Ca(2+)-responsiveness of release (which for Rims gene mutants is a measure of presynaptic Ca(2+) influx). Moreover, single deletions did not affect the synchronization of release (which depends on the close proximity of Ca(2+) channels to release sites). In contrast, deletion of both Rims genes severely impaired the Ca(2+) responsiveness and synchronization of release. RIM proteins may act on Ca(2+) channels in two modes: They tether Ca(2+) channels to active zones, and they directly modulate Ca(2+)-channel inactivation. The first mechanism is essential for localizing presynaptic Ca(2+) influx to nerve terminals, but the role of the second mechanism remains unknown. Strikingly, we find that although the RIM2 C(2)B domain by itself significantly decreased Ca(2+)-channel inactivation in transfected HEK293 cells, it did not rescue any aspect of the RIM knockout phenotype in cultured neurons. Thus, RIMs primarily act in release as physical Ca(2+)-channel tethers and not as Ca(2+)-channel modulators. Different RIM proteins compensate for each other in recruiting Ca(2+) channels to active zones, but contribute independently and incrementally to vesicle priming.     

GDNF促进帕金森病大鼠模型脑内移植的中脑源神经干细胞表达Pitx3、Nurr1和TH

目的:探讨胶质细胞源性神经营养因子(GDNF)作用下,中脑源神经干细胞(mNSCs)在帕金森病(PD)大鼠模型纹状体移植区表达垂体同源盒家族因子3(Pitx3)、孤儿核受体相关因子1(Nurr1)和酪氨酸羟化酶(TH)的变化.方法:mNSCs单独移植组、mNSCs+GDNF移植组和生理盐水假手术组的PD大鼠模型,移植4...     

Grafting antibiofilm polymer hydrogel film onto catheter by SARA SI-ATRP

Abstract

Catheters are widely used and play an important role in medicine. However, catheter-associated infection is prevalent even under stringent sterile conditions. Biofilms are formed when bacteria populate the surfaces of catheters. This makes the biofilm resistant to antibiotics. Hence, it is imperative for there to be an inherently antifouling and anti-bacterial catheter to mitigate the formation of biofilm. This paper aims to outline the synthesis of non-leachable anti-biofilm and anti-bacterial cationic film coatings through direct polymerization using supplemental activator and reducing agent surface initiated atom transfer radical polymerization (SARA SI-ATRP). Three crosslinked cationic coatings comprising of Diallyl dimethyl ammonium chloride (DADMAC), or ε-poly-L-lysine HCl methacrylic acid (EPL-MA) together with a crosslinker (polyethylene glycol dimethacrylate, PEGDMA) were investigated. These non-leachable covalently linked coatings with DADMAC can achieve more than 2 log reduction (99.0%) with Methicillin-resistant Staphylococcus aureus (MRSA) and 1.25 log reduction (94.4%) with Vancomycin resistant Enterococcus (VRE) in in vitro studies.     

自发性颈动脉海绵窦瘘的介入治疗

目的 探讨自发性颈动脉海绵窦瘘的诊治方法。方法 9例单纯颈内动脉供血,其中6例采取球囊瘘内闭塞术,3例采用瘘口一同闭塞的颈内动脉闭塞术。11例采用微导管超选择性插管,行瘘的供血动脉及瘘口栓塞。栓塞后7例仍有供血者3例经压颈1个月瘘口消失,2例疗效不满意,患者未再来治疗,2例采取经岩下窦途径和经眼静脉途径。1例单纯由颈内动脉脑膜支供血的行γ刀治疗。结果 13例栓塞后造影瘘口完全闭塞,7例栓塞后造影瘘口有显影,术后采取压迫患侧颈总动脉1个月,半年后3例造影瘘口消失,2例疗效不满意,失去随访,2例经眼静脉、岩下窦栓塞海绵窦取得成功。γ刀治疗1例,症状消失。19例随访6个月未见瘘口再通。结论 介入栓塞是治疗自发性颈动脉海绵窦瘘行之有效的方法。     

精神分裂症患者颞上回的大麻素受体密度没有显著性变化

目的 近年来研究发现,在精神分裂症患者的内源性大麻素递质系统会出现异常变化,而颞上回在精神分裂症的病理生理机制中和幻听症状密切相关.因此,对照正常人群,我们研究了精神分裂症患者颞上回大麻素CB-1受体的密度变化.方法 采用定量放射自显影技术,通过[3H]SR141716A(CB-1受体选择性拮抗剂)和[3H]CP-55940(CB-1受体激动剂)检测颞上回CB-1受体密度水平.死后脑组织由澳大利亚新南威尔士州组织资源中心提供.结果 先前研究发现,精神分裂症患者与认知功能失常相关的额前叶,前、后扣带回皮质的CB-1受体密度水平有异常改变.与此相反,本研究发现在精神分裂症患者的由[3H]SR141716A和[3H]CP-55940检测的颞上回大麻素受体密度水平和对照组比较没有显著变化.结论 我们认为颞上回大麻素CB-1受体和精神分裂症患者的发病及幻听症状无关.     

Relationship between liver fibrosis criteria and syndrome-type of TCM in patients with non-alcoholic fatty liver

To explore the relationship between the liver fibrosis criteria and TCM Syndrome type in patients suffering from non-alcoholic fatty liver. Methods: Seventy-nine patients with non-alcoholic fatty liver diagnosed by B ultrasonography were classified by TCM Syndrome Differentiation and their liver fibrosis criteria was determined and compared with those of the healthy subjects as control. Results: Levels of procollagen Ⅲ (PCⅢ), hyaluronic acid (HA), collagen Ⅳ(CⅣ) and laminin (LN) in the fatty liver group were significantly higher than those in the control group (P＜0.05, P＜0.01). In respect to the TCM Syndrome-types, PCⅢ, CⅣ and LN in patients of Phlegm-stasis combined type were significantly higher than those in patients of Spleen deficiency-Phlegm dampness Syndrome-type and Damp-Heat Syndrome-type (P＜0.05, P＜0.01), while HA in different groups was insignificantly different (P＞0.05). Conclusion: There was trend of liver fibrosis in fatty liver patients. It was indicated that the Phlegm-stasis combined Syndrome-type possibly was the main TCM pathologic factor of the increasing of fibrosis criteria for non-alcoholic fatty liver.     

丙型肝炎病毒感染对肾移植术后影响的临床研究

OBJECTIVE: To study the influence of hepatitis C virus (HCV) infection on the clinical outcome of kidney transplantation. METHODS: The recipient/graft survival, the incidence of acute/chronic rejection and cause of death in 86 HCV-infected recipients of renal transplantation were compared with those in another 86 recipients without HCV infection. RESULTS: HCV-infected recipients had significantly shorter 5-year survival (74.4%) than those without HCV infection (87.2%, P<0.01). The 1-year (94.2%/90.7% vs 96.8%/96.0%) and 3-year recipient/graft survival rates (88.4%/79.1% vs 90.7%/87.2%), the incidence of acute/chronic rejection (31.3% vs 21.2%, and 12.5% vs 6.5%) and the 5-year graft survival (73.3%/81.4%) were comparable between the two groups (P>0.05). Hepatic disease was identified as the primary cause of mortality. CONCLUSIONS: HCV infection may affect the long-term survival of the recipients with kidney transplantation, and therefore should be considered as a relative contraindication of kidney transplantation.