Spindles and active vortices in a model of confined filament-motor mixtures

Background

Although biological membranes are organized as lipid bilayers, they contain a substantial fraction of lipids that have a strong tendency to adopt a nonlamellar, most often inverted hexagonal (H_II) phase. The polymorphic phase behavior of such nonbilayer lipids has been studied previously with a variety of methods in the fully hydrated state or at different degrees of dehydration. Here, we present a study of the thermotropic phase behavior of the nonbilayer lipids egg phosphatidylethanolamine (EPE) and monogalactosyldiacylglycerol (MGDG) with a focus on interactions between the lipid molecules in the interfacial and headgroup regions.

Results

Liposomes were investigated in the dry state by Fourier-transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry (DSC). Dry EPE showed a gel to liquid-crystalline phase transition below 0°C and a liquid-crystalline to H_II transition at 100°C. MGDG, on the other hand, was in the liquid-crystalline phase down to -30°C and showed a nonbilayer transition at about 85°C. Mixtures (1:1 by mass) with two different phosphatidylcholines (PC) formed bilayers with no evidence for nonbilayer transitions up to 120°C. FTIR spectroscopy revealed complex interactions between the nonbilayer lipids and PC. Strong H-bonding interactions occurred between the sugar headgroup of MGDG and the phosphate, carbonyl and choline groups of PC. Similarly, the ethanolamine moiety of EPE was H-bonded to the carbonyl and choline groups of PC and probably interacted through charge pairing with the phosphate group.

Conclusions

This study provides a comprehensive characterization of dry membranes containing the two most important nonbilayer lipids (PE and MGDG) in living cells. These data will be of particular relevance for the analysis of interactions between membranes and low molecular weight solutes or soluble proteins that are presumably involved in cellular protection during anhydrobiosis.     

Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation

Hildebrand MS, Thorne NP, Bromhead CJ, Kahrizi K, Webster JA, Fattahi Z, Bataejad M, Kimberling WJ, Stephan D, Najmabadi H, Bahlo M, Smith RJH. Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation. Myosin VIIA mutations have been associated with non‐syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyses of a consanguineous Iranian family segregating autosomal recessive non‐syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L‐1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. As one affected family member had significantly less severe hearing loss, we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non‐syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders.     

苏皖地区汉族人群不稳定型心绞痛患者与血小板反应素4基因A387P多态性的关系

目的:观察血小板反应素4基因G29926C(A387P)多态性与中国苏皖地区汉族人群不稳定型心绞痛的可能关系。方法:选择2004-11/2006-05在南京医科大学第一附属医院和江苏大学附属武进医院住院不稳定型心绞痛患者110例,病例均符合2002年AHA/ACC关于不稳定型心绞痛诊断指南的诊断标准,同期选择337例非冠心病者为对照。酚-氯仿法提取白细胞DNA,应用聚合酶链反应-限制性片段长度多态性方法分析血小板反应素4A387P多态性,取部分PCR扩增产物进一步测序鉴定,比较两组间多态性频率分布差异,探讨血小板反应素4基因多态性与不稳定型心绞痛发病的可能关系。结果:447例均进入结果分析。GC基因型在不稳定型心绞痛组和对照组的分布无统计学差异(5.5%,7.1%,P=0.54),未检测到CC纯合子。C等位基因频率在不稳定型心绞痛组和对照组分别为2.7%,3.6%(P=0.55)。GC基因型与不稳定型心绞痛无显著性关联(OR=0.75,95%CI:0.30￣1.89,P=0.54)。结论:血小板反应素4基因387A→P不是中国苏皖地区汉族人群常见的多态位点,且与不稳定型心绞痛的发病无显著相关性。     

针灸在多囊卵巢综合征患者宫腔内人工授精助孕术中的应用

目的:通过对近10年相关文献的研究,总结针灸在多囊卵巢综合征患者宫腔内人工授精助孕术中的影响以及在此方面的应用。方法:检索中国期刊全文数据库1996-01/2006-06与针灸对多囊卵巢综合征患者的影响有关的文章,检索词为"针灸,多囊卵巢综合征,人工授精助孕术",限定文章语言种类为中文。同时检索Elsevier-SDOL数据库1996-01/2006-06的相关文章,检索词为"acupuncture,polycystic ovary syndrome,intrauterine insemination",限定文章语言种类为英文。结果:选取文章应该是在下列范围内:针灸对多囊卵巢综合征患者的影响、针灸在宫腔内人工授精助孕术中的应用、多囊卵巢综合征患者在行宫腔内人工授精助孕术时的影响因素以及有关针灸在此方面的研究。共收集到200篇关于"针灸对多囊卵巢综合征患者的影响"的文章,300篇关于"多囊卵巢综合征患者在行宫腔内人工授精助孕术时的影响因素"的文章,30篇关于"针灸在宫腔内人工授精助孕术中的应用"的文章,16篇符合本文标准。既往大多数研究是集中在关于针灸治疗多囊卵巢综合征以及针灸促排卵的临床研究上,认为针灸可以有效治疗多囊卵巢综合征,还可以通过对卵巢的刺激作用而达到促进排卵的作用,并一致认为针灸促排卵不但无副作用而且疗效好,作用稳定、持久。另外曾有德国学者发现将针灸疗法应用于辅助体外授精或精子卵浆内注射技术中,其怀孕成功机率提高近50%。然而,关于针灸在多囊卵巢综合征患者宫腔内人工授精助孕技术中的应用国内外却均未见报道。结论:宫腔内人工授精助孕术已经广泛应用于不孕症的治疗中,而针灸又有很好的促排卵作用。因此可以尝试在多囊卵巢综合征患者行宫腔内人工授精术前后加用针灸疗法,从而研究针灸辅助卵巢诱导排卵在多囊卵巢综合征患者行宫腔内人工授精中的应用,观察针灸是否可以提高多囊卵巢综合征患者的宫腔内人工授精助孕术的成功率。     

腺相关病毒介导癌胚抗原转染树突状细胞对免疫功能的调节作用

目的:近年来,树突状细胞参与调节作用的研究较多。实验拟验证重组腺相关病毒(rAAV)介导癌胚抗原基因转染树突状细胞后其的免疫调节作用的变化。方法:实验于2006-06/2006-11在美国阿肯色大学医学院基因治疗中心完成。①实验方法:取健康人外周血(自愿捐献),采用改良Ficoll密度梯度离心的方法分离外周血单个核细胞,取贴壁细胞,分为rAAV/CEA转染组和空白对照组,均采用重组人粒细胞巨噬细胞集落刺激因子、白细胞介素4、肿瘤坏死因子-α诱导树突状细胞前体细胞成熟,将成熟树突状细胞与末梢血淋巴细胞按比例混合培养,可得到激活的细胞毒性T淋巴细胞。②实验评估:采用流式细胞仪检测树突状细胞表面标志表达,细胞毒性T淋巴细胞的免疫表型变化,细胞毒性T淋巴细胞γ-干扰素表达。采用酶联免疫吸附法(ELISA法)检测树突状细胞的白细胞介素12和白细胞介素10表达。结果:①rAAV/CEA转染树突状细胞的CD14较空白对照组降低,共刺激分子CD40、CD80、CD83、CD86表达均较空白对照组高。②成熟树突状细胞细胞因子表达中,rAAV/CEA转染组的白细胞介素12较空白对照组升高,白细胞介素10降低。③与空白对照组比较,rAAV/CEA转染组能高表达CD8 T细胞和其表型CD69,CD8/CD56的T细胞比例上调,CD25 CD4 的T细胞减少。④rAAV/CEA转染的细胞毒性T淋巴细胞表达相对较高水平的γ-干扰素,与杀伤实验结果相吻合。结论:rAAV/CEA转染树突状细胞能够激活细胞毒性T淋巴细胞的特异性杀伤作用,与树突状细胞和细胞毒性T淋巴细胞等免疫细胞表面标志变化和细胞内细胞因子水平变化相关。     

硫酸锌对心肌慢反应电活动和哇巴因引起振荡后电位的影响

本文目的旨在观察硫酸锌对心肌慢反应电活动的影响,所得结果如下:(1) 0.1～0.3mmol硫酸锌能使高钾除极引起的豚鼠乳头肌慢反应动作电位APA和V_max降低,APD₅₀和APD₉₀)显著延长;(2) 0.1～0.3 mmol硫酸锌能抑制家兔离体窦房结细胞的自律性,使窦房结APA降低,APD₉₀延长,SP₀和SP₄减小;(3) 0.1 mmol硫酸锌可对抗0.4μmol哇巴因诱发的豚鼠心室肌振荡后电位,提高引起振荡后电位的哇巴因阈浓度。提示:锌抑制心肌慢反应电活动。     

清热中药对大鼠下丘脑组织AVP含量的影响

目的：清热中药大多具有一定的解热作用,为探讨其解热作用机理,我们选用典型的清热中药黄芩,银花,连翘组成清热方,从体温调节中枢神经介质方面来研究其解热作用机制。方法;选用Ｗｉｓｔａｒ大鼠,按体重随机分作３组,背部皮下注射酵母混悬液制造发热模型,给药组灌服清热方颗粒剂,模型组予等量饮用水,正常对照组不作处理,给药２ｈ后断头取脑,用放免方法检测大鼠下丘脑组织中ＡＶＰ含量。结果：模型组大鼠体温和下丘脑组织     

楤木根皮中皂甙化学成分的研究

楤木根皮中的主要成分是皂甙。将总皂甙以柱层析分离,得到三个化合物(Ⅰ～Ⅲ),经光谱分析和化学方法证明,Ⅰ为楤木皂甙A(araloside A);Ⅱ为银莲花甙(narcissiflorine);Ⅲ是3-O-[β-D-吡喃葡萄糖-(1→2)-β-D-吡喃木糖-(1→)2)-α-L-阿拉伯糖]-齐墩果酸。Ⅲ为一新皂甙,命名为楤木皂甙D(araloside D)。     

反相高效液相色谱法测定甲磺酸酚妥拉明片的含量

目的：建立了反向高效液相色谱法测定甲磺酸酚妥拉明的含量的方法。方法：采用Symmetry C18硅烷键和硅胶柱,甲醇－水－冰醋酸－三乙胺（10：10：1：0．1）作为流动相,检测波长为278nm,峰面积外标法测定。结果：平均回收率为100．2％（n=11),日内、日间差分别为0．7％和0．8％,在10－250μg范围内线性关系良好（r=0.9999),结论：该法简便、准确、结果满意。     

A comparison of DNA sequencing and gene expression profiling to assist tissue of origin diagnosis in cancer of unknown primary

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high–medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs – 80% had high–medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high–medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.