Synthesis and structure–activity relationship of a novel series of heterocyclic sulfonamide γ-secretase inhibitors

γ-Secretase inhibitors have been shown to reduce the production of β-amyloid, a component of the plaques that are found in brains of patients with Alzheimer’s disease. A novel series of heterocyclic sulfonamide γ-secretase inhibitors that reduce β-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative γ-secretase substrate.     

(S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor

Accumulation of beta-amyloid (Aβ), produced by the proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretase, is widely believed to be associated with Alzheimer’s disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) γ-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaninol 7.b.2 (Aβ _40/42 EC₅₀ = 28 nM), which is efficacious in reduction of Aβ production in vivo.     

Probiotic Microbes Sustain Youthful Serum Testosterone Levels and Testicular Size in Aging Mice

The decline of circulating testosterone levels in aging men is associated with adverse health effects. During studies of probiotic bacteria and obesity, we discovered that male mice routinely consuming purified lactic acid bacteria originally isolated from human milk had larger testicles and increased serum testosterone levels compared to their age-matched controls. Further investigation using microscopy-assisted histomorphometry of testicular tissue showed that mice consuming Lactobacillus reuteri in their drinking water had significantly increased seminiferous tubule cross-sectional profiles and increased spermatogenesis and Leydig cell numbers per testis when compared with matched diet counterparts This showed that criteria of gonadal aging were reduced after routinely consuming a purified microbe such as L. reuteri. We tested whether these features typical of sustained reproductive fitness may be due to anti-inflammatory properties of L. reuteri, and found that testicular mass and other indicators typical of old age were similarly restored to youthful levels using systemic administration of antibodies blocking pro-inflammatory cytokine interleukin-17A. This indicated that uncontrolled host inflammatory responses contributed to the testicular atrophy phenotype in aged mice. Reduced circulating testosterone levels have been implicated in many adverse effects; dietary L. reuteri or other probiotic supplementation may provide a viable natural approach to prevention of male hypogonadism, absent the controversy and side-effects of traditional therapies, and yield practical options for management of disorders typically associated with normal aging. These novel findings suggest a potential high impact for microbe therapy in public health by imparting hormonal and gonad features of reproductive fitness typical of much younger healthy individuals.     

绿色荧光蛋白(ZsGreen)基因在长石莼细胞中的表达

主要研究绿色荧光蛋白(ZsGreen)基因在长石莼(缘管浒苔)细胞中的表述.应用绿色荧光蛋白基因、抗除草剂bar基因、CMV 35S启动子和SV40双启动子构建了质粒载体PSV-bar-ZsGeen,采用改进的PEG法将质粒载体PSV-bar-Zs-Geen导入到缘管浒苔原生质体中,经过细胞培养发育再生藻株,通过除草剂筛选出阳性藻株,且转化率达38.58％,进一步PCR分子检测和显微荧光检测表明,绿色荧光蛋白基因在转基因植株中得到表达,为今后转基因浒苔研究奠定基础.     

扬子鳄颈髓一氧化氮合酶(NOS)和乙酰胆碱酯酶(AChE)阳性神经元的分布

本实验分别应用还原型尼克酰胺嘌呤二核苷酸脱氢酶（ＮＡＤＰＨ－ｄ）和乙酰胆碱酯酶（ＡＣｈＥ）方法,对扬子鳄颈髓ＮＯＳ和ＡＣｈＥ阳性神经元的分布进行了研究。结果表明：颈髓前角、中央灰质均含有ＮＯＳ和ＡＣｈＥ阳性神经元,颈髓后角有较为丰富的ＮＯＳ和ＡＣｈＥ阳性纤维和终末以及显色淡的ＮＯＳ阳性神经元。     

不同途径感染白斑综合征病毒 (WSSV) 对日本沼虾的致病性

日本沼虾肉质鲜美、经济价值高,但其对白斑综合征病毒(White spot syndrome virus,WSSV)的易感性尚不明确。采用流行病学调查、感染试验和荧光定量PCR(qPCR)等方法,研究了日本沼虾Macrobrachium nipponense对WSSV的易感性、感染发病率以及WSSV在其体内的增殖情况。结果表明:日本沼虾是WSSV的自然宿主,上海市附近省份地区120个样本的自然携带率为8.33%。日本沼虾可以通过注射、摄食、浸泡途径感染WSSV,10 d内累计感染率均为100%,累计死亡率分别为100%、75%和0%。其中注射途径感染日本沼虾,感染后5 d肌肉病毒含量达到感染后1 d的1 000倍,8 d死亡率达100%。用注射WSSV感染日本沼虾死亡率来测量病毒致死日本沼虾的半数致死剂量(LD_(50)),2.71×10~5病毒粒子/μL能使日本沼虾死亡率达到50%以上。在养殖生产中,日本沼虾可以通过摄食感染WSSV的病虾或死虾而感染WSSV,也能通过浸泡在含WSSV的水体中而感染,并因此成为一种传播媒介,从而影响了WSSV的迅速传播与致病。     

微藻规模化培养研究进展

微藻作为地球上最古老的物种之一,其诞生可追溯到35亿多年前.微藻的种类十分丰富,形态也多种多样.微藻一般都含有叶绿体,因此可进行光合作用,有研究表明微藻固定CO2的能力是陆地植物的10倍.微藻以其丰富的代谢产物及独特的生理特性在可再生能源、生物医药、食品工业和环境监测等方面有着广泛的应用.然而如何在控制成本的前提下对微...     

硫酸铵三步盐析对藻胆蛋白纯化的影响

主要研究了多次硫酸铵盐析对条斑紫菜藻胆蛋白提取纯化效果。对分离提取的对条斑紫菜藻胆蛋白溶液进行了3次硫酸氨溶液盐析,实验结果表明:55%饱和度可以将绝大部分藻胆蛋白盐析;采用不同组合(15%、20%、25%、30%、35%、40%、45%7个饱和度分别与50%、55%、60%3个饱和度两两组合)二步硫酸铵盐析沉淀藻胆蛋白,使R-藻红蛋白和C-藻蓝蛋白的盐析后纯度(A564/A280)分别达到了1.0和0.45以上,得率分别为1.4%和0.95%;第3次硫酸铵盐析使R-藻红蛋白、C-藻蓝蛋白的纯度分别达到了1.4和0.4以上,最终产率分别为1.3%和0.8%,而变藻蓝蛋白产率有所下降(从0.65%到0.49%),但纯度变化不大。实验证明了采用多次盐析方法可以很大程度提高藻胆蛋白纯度。     

东太湖水生植被及其沼泽化趋势

１９９６年东太湖水生植被调查结果表明,沉水植被、挺水植被及浮叶植被面积分别为７３．８、４５．５和６．７ｋｍ２。有９个群丛,其中微齿眼子菜（Ｐｏｔａｍｏｇｅｔｏｎｍａａｃｋｉａｎｕｓ）群丛、菰（Ｚｉｚａｎｉａｌａｔｉｆｏｌｉａ）群丛、伊乐藻微齿眼子菜（ＥｌｏｄｅａｎｕｔａｌｉＰｏｔａｍｏｇｅｔｏｎｍａａｃｋｉａｎｕｓ）群丛和芦苇（Ｐｈｒａｇｍｉｔｅｓｃｏｍｍｕｎｉｓ）群丛分布面积较大,分别占东太湖总面积的３９３９％、２８２７％、１１２０％和６４０％。与１９６０年相比,水生植被变化极为明显,突出表现为环湖水陆交错带的芦苇群丛严重退化和消失,菰群丛发展迅速并向湖心蔓延占据了东太湖总面积的２８２７％;微齿眼子菜取代了竹叶眼子菜（Ｐｏｔａｍｏｇｅｔｏｎｍａｌａｉａｎｕｓ）、黑藻（Ｈｙｄｒｉｌａｖｅｒｔｉｃｉｌａｔａ）及苦草（Ｖａｌｉｓｎｅｒｉａｎａｔａｎｓ）,成为沉水植被的优势种,占据了东太湖整个湖心区;外来种伊乐藻（Ｅｌｏｄｅａｎｕｔａｌｉ）侵入,并形成一定规模的群丛。综观该湖区水生植被演化过程,可知东太湖已经出现沼泽化趋势,应引起足够重视