Evolution of transmission mode in conditional mutualisms with spatial variation in symbiont quality

Many symbioses have costs and benefits to their hosts that vary with the environmental context, which itself may vary in space. The same symbiont may be a mutualist in one location and a parasite in another. Such spatially conditional mutualisms pose a dilemma for hosts, who might evolve (higher or lower) horizontal or vertical transmission to increase their chances of being infected only where the symbiont is beneficial. To determine how transmission in hosts might evolve, we modeled transmission evolution where the symbiont had a spatially conditional effect on either host lifespan or fecundity. We found that over ecological time, symbionts that affected lifespan but not fecundity led to high frequencies of infected hosts in areas where the symbiont was beneficial and low frequencies elsewhere. In response, hosts evolved increased horizontal transmission only when the symbiont affected lifespan. We also modeled transmission evolution in symbionts, which evolved high horizontal and vertical transmission, indicating a possible host–symbiont conflict over transmission mode. Our results suggest an eco‐evolutionary feedback where the component of host fitness affected by a conditionally mutualistic symbiont in turn determines its distribution in the population, and, through this, the transmission mode that evolves.     

The role of infectious disease in the evolution of females: Evidence from anther‐smut disease on a gynodioecious alpine carnation*

In flowering plants, the evolution of females is widely hypothesized to be the first step in the evolutionary pathway to separate male and female sexes, or dioecy. Natural enemies have the potential to drive this evolution if they preferentially attack hermaphrodites over females. We studied sex‐based differences in exposure to anther‐smut (Microbotryum), a sterilizing pollinator‐transmitted disease, in Dianthus pavonius, a gynodioecious perennial herb. We found that within a heavily diseased population, females consistently had lower levels of Microbotryum spore deposition relative to hermaphrodites and that this difference was driven by rapid floral closing in females following successful pollination. We further show that this protective closing behavior is frequency dependent; females close faster when they are rare. These results indicate that anther‐smut disease is an important source of selection for females, especially since we found in a common garden experiment no evidence that females have any inherent fecundity advantages over hermaphrodites. Finally, we show that among populations, those where anther‐smut is present have a significantly higher frequency of females than those where the disease is absent. Taken together our results indicate that anther‐smut disease is likely an important biotic factor driving the evolution and maintenance of females in this gynodioecious species.     

鼻病毒非结构蛋白2B 诱导细胞发生内质网应激

为探讨鼻病毒非结构蛋白2B诱导内质网应激和细胞凋亡的机制,本研究构建了鼻病毒非结构蛋白2B的真核表达载体p2B‐GFP ,通过转染BHK‐21细胞检测相关标志蛋白的变化情况。结果显示,非结构蛋白2B定位表达于BHK‐21细胞内质网,诱导内质网应激标志蛋白Grp78、CHOP的表达增加,并使活化转录因子6（ATF6）的转录活性增加,还诱导BHK‐21细胞发生核浓缩而凋亡,使凋亡标志蛋白PARP发生降解而减少。结果提示,鼻病毒非结构蛋白2B可诱导细胞发生内质网应激,并经该途径诱导细胞凋亡。     

大剂量瑞舒伐他汀钙治疗老年冠心病合并高脂血症的疗效观察

目的:研究大剂量瑞舒伐他汀钙治疗老年冠心病合并高脂血症的临床疗效。方法:选取2013年10月到2014年10月我院收治的老年冠心病合并高脂血症患者110例,按照随机数字表法将患者分为研究组和对照组,每组55例。两组患者均给予常规治疗方法进行治疗,对照组增加5 mg瑞舒伐他汀钙进行治疗,研究组增加20 mg瑞舒伐他汀钙进行治疗,均每天1次,晚餐后应用,治疗时间为4个月。比较治疗前后两组血脂水平(胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C))及高密度脂蛋白(HDL-C)及其达标率以及不良反应。结果:治疗后两组TC、TG以及LDL-C均显著降低,HDL-C显著升高,且研究组优于对照组,比较差异具有统计学意义(P0.05);研究组治疗后TC和LDL-C达标率显著高于对照组,两组比较差异具有统计学意义(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05)。结论:大剂量瑞舒伐他汀钙治疗老年冠心病合并高脂血症具有较好的临床疗效,能显著降低患者的血脂水平。     

PP2 对人胆管癌细胞株QBC939 侵袭能力的影响

目的：探讨Src 激酶特异性抑制剂PP2 对人胆管癌QBC939 细胞侵袭能力的影响和机制。方法：通过Western Blotting 技术 检测PP2 对人胆管癌QBC939细胞中Src 激酶活化的影响;用Transwell 小室法观察PP2 对QBC939细胞的影响;用RT-PCR 和 Western Blotting 技术检测PP2对QBC939 细胞侵袭能力相关分子的作用。结果：实验组p-Src 蛋白表达水平明显低于对照组,差 异具有统计学意义（P<0.05）;实验组QBC939 细胞体外侵袭能力较对照组显著降低,差异具有统计学意义（P<0.05）;与对照组相 比,实验组E-cadherin 表达显著增强,CD44表达明显减弱,差异具有统计学意义（P<0.05）。结论：PP2 通过抑制Src 激酶活化,增 强E-cadherin 表达、减弱CD44 表达,抑制人胆管癌QBC939 细胞侵袭能力。     

醒脑静注射液联合血府逐瘀汤对SAH大鼠CRP、TNF-alpha的影响

目的：探讨醒脑静注射液联合血府逐瘀汤对蛛网膜下腔出血（subarachnoidhemorrhage,SAH）大鼠C反应蛋白(C-reactionprotein, CRP) 、肿瘤坏死因子-a（Tumor necrosis factor-a,TNF-a）的影响。方法：50 只大鼠随机分为5 组：正常组,模型组,醒脑静组 （0.3 mL/kg）,血府逐瘀汤组（0.3 mL/kg）,联合用药组（醒脑静联合血府逐瘀汤）。除正常组外,其余4组采用" 二次枕大池注血法" 建立大鼠SAH 模型。从造模成功后的第1 d 开始给药,连续给药7 d。正常对照组及模型组给予等量生理盐水。分别在术前、术后 1 d、3 d、7 d、14 d取血浆及脑脊液,按ELISA 试剂盒说明书分别测定各组血清及脑脊液中肿瘤坏死因子-alpha（TNF-alpha）、C- 反应蛋白 （CRP）的含量。结果：（1）术后随着时间推移,SAH大鼠血清及脑脊液中TNF-alpha及CRP 含量逐渐上升,在第7 d 达到高峰。（2）术 后第1 d,与正常组比较,模型组中血清及脑脊液中TNF-琢、CRP含量均显著上升,差异显著（P<0.01）;与模型组比较,醒脑静组及 血府逐瘀汤组中血清及脑脊液中TNF-alpha、CRP 含量无差异（P>0.05）,而联合用药组中血清及脑脊液中TNF-琢含量下降,差异具有 显著意义（P<0.05）。（3）术后第3 d、7 d、14 d,与正常组比较,模型组中血清及脑脊液中TNF-琢、CRP 含量均显著上升,差异显著 （P<0.01）;与模型组比较,醒脑静组、血府逐瘀汤组及联合用药组中血清及脑脊液中TNF-琢、CRP 含量下降,差异均显著（P<0.0 1）,与醒脑静组或血府逐瘀汤组比较,联合用药组中血清及脑脊液中TNF-alpha、CRP含量下降,差异均显著（P<0.05）。结论：醒脑静 联合血府逐瘀汤能有效缓解SAH大鼠CVS,与降低SAH大鼠血清及脑脊中TNF-alpha、CRP 水平有关。     

重症肺炎患者PCT,WBC,CRP水平与预后的相关性分析

目的:探讨重症肺炎患者降钙素原(PCT)、白细胞(WBC)、C-反应蛋白(CRP)水平与疾病的相关性。方法:回顾性分析我院ICU收治的101例重症肺炎患者,患者均采取机械通气治疗,根据生存情况分为分为生存组与死亡组,另选取同期体检的正常人共40例作为对照组。在住院时、入院后第1 d、5 d以及转出ICU(或死亡时)抽取外周血检测血清PCT、WBC以及CRP水平,同时进行APACHEⅡ评分,并应用统计学分析方法进行数据的相关性分析。结果:1与正常人群相比,重症肺炎患者的PCT、WBC以及CRP显著升高,与死亡组同期比较,生存组PCT、WBC以及CRP较低,P0.05;2与死亡组同期比较,生存组APACHEⅡ评分较低,P0.05;3相关性分析结果显示WBC、CRP、PCT与APACHEⅡ评分呈正相关P0.01。结论:重症肺炎患者的血清PCT、WBC以及CRP水平升高明显,有利于判断重症肺炎病情,对评估预后具有一定的价值。     

sTACI-Fc-Myc重组质粒的构建、原核表达及活性鉴定

目的:构建s TACI-Fc-Myc重组质粒,并进行原核表达和纯化具有生物活性的融合蛋白。方法:通过PCR法获得s TACI-Fc-Myc重组片段,然后把融合基因片段与原核载体p ET28a连接在一起,并构建p ET28a-s TACI-Fc-Myc重组子,并转入BL21(DE3)中进行表达,用蛋白A凝胶亲和层析柱进行纯化及酶联免疫吸附剂(ELISA)法测定其生物学活性。结果:获得了s TACI-Fc-Myc重组质粒,且该质粒可以在BL21(DE3)中表达,亲和层析柱纯化后纯度可达到95%以上,与BAFF的结合活性具有剂量依赖性,浓度达到5 ng/μL时,两者的吸附达到饱和。结论:成功构建了s TACI-Fc-Myc原核表达载体,并使有生物学活性的融合蛋白在BL21(DE3)上获得了稳定表达,为进一步研究并筛选高活性BAFF拮抗肽奠定了基础。     

Effects of low dietary protein on the metabolites and microbial communities in the caecal digesta of piglets

Thirty-six healthy piglets (weighing 10 ± 1 kg; three animals per pen) were randomly allocated to two treatments: (i) a low protein diet (14% crude protein [CP]) supplemented with lysine, methionine, threonine and tryptophan (Group LP) and (ii) a normal protein diet (20% CP, Group NP), resulting in six replicate pens per treatment. One piglet from each pen was slaughtered at days 10, 25 and 45 of the experiment. For the whole experimental period of 45 d, Group LP had lower feed intake and daily gain and a higher feed-to-gain ratio compared with Group NP. At day 10, no effects on measured caecum metabolites were observed, but at days 25 and 45 in Group LP the concentration of ammonia-N, cadaverine, branched chain fatty acids and acetate were reduced. This was also true for the concentration of short chain fatty acids at day 45. The results of denaturing gradient gel electrophoresis showed that microbial diversity in Group LP was less abundant at day 25, but there was no difference at days 10 and 45. An unweighted pair group mean average analysis showed that the similarities were lower between Groups LP and NP at day 10 and higher at days 25 and 45. Quantitation results indicated that the numbers of Firmicutes and Clostridium cluster IV were lower in Group LP than in Group NP at day 25, but there were no differences at days 10 and 45. In conclusion, the low protein diet markedly reduced the metabolites of protein and carbohydrate fermentation and altered microbial communities in the caecal digesta of piglets.     

A novel BH3 mimetic efficiently induces apoptosis in melanoma cells through direct binding to anti‐apoptotic Bcl‐2 family proteins,including phosphorylated Mcl‐1

The Bcl‐2 family modulates sensitivity to chemotherapy in many cancers, including melanoma, in which the RAS/BRAF/MEK/ERK pathway is constitutively activated. Mcl‐1, a major anti‐apoptotic protein in the Bcl‐2 family, is extensively expressed in melanoma and contributes to melanoma's well‐documented chemoresistance. Here, we provide the first evidence that Mcl‐1 phosphorylation at T163 by ERK1/2 and JNK is associated with the resistance of melanoma cell lines to the existing BH3 mimetics gossypol, S1 and ABT‐737, and a novel anti‐apoptotic mechanism of phosphorylated Mcl‐1 (pMcl‐1) is revealed. pMcl‐1 antagonized the known BH3 mimetics by sequestering pro‐apoptotic proteins that were released from Bcl‐2/Mcl‐1. Furthermore, an anthraquinone BH3 mimetic, compound 6, was identified to be the first small molecule to that induces endogenous apoptosis in melanoma cells by directly binding Bcl‐2, Mcl‐1, and pMcl‐1 and disrupting the heterodimers of these proteins. Although compound 6 induced upregulation of the pro‐apoptotic protein Noxa, its apoptotic induction was independent of Noxa. These data reveal the promising therapeutic potential of targeting pMcl‐1 to treat melanoma. Compound 6 is therefore a potent drug that targets pMcl‐1 in melanoma.