Microarray analysis of microRNA expression in liver cancer tissues and normal control

Background

Recently, many studies have focused on microRNAs (miRNAs) expression profiling in liver cancer, due to the ability of these small RNAs to potently influence cellular behavior. In this study, to further investigate the relationship between them, the miRNA expression profiling of the cancer liver tissues and normal liver tissues were compared.

Methods

The datasets of miRNAs microarray in liver cancer and normal control were downloaded from Gene Expression Omnibus. Then the SOAP analysis was performed to identify the differentially expressed miRNAs.

Results

A total of 221 differentially expressed miRNAs were found. Five of them (including hsa-miR-15b, hsa-miR-1975, hsa-miR-199a-3p, hsa-miR-199b-3p and hsa-miR-421) were determined by t-test and may be involved in the pathogenesis of liver cancer.

Conclusion

There differentially expressed miRNAs may be potential molecular markers for liver cancer screening.     

Photochemical Products Obtained from Jasmone

Acremoauxin A, a new fungal auxin derivative produced by A. roseum I 4267, was synthesized from indole, lactic acid, and d-mannitol. (+)-2-(3-Indolyl)propionic acid was prepared from its synthetic racemate by biological resolution using the acremoauxin-producing fungus. The synthetically confirmed structure of acremoauxin A was 1-O-[(2S)-(+)-2-(3-indolyl)propionyl]-d-arabitol (1).     

湖南新宁野生藤本植物组成及多样性分析

采用实地调查、标本采集和查证相结合的方法,对湖南新宁野生藤本植物组成及多样性进行了研究。结果表明：新宁共有野生藤本植物49科111属354种,分别占该区域植物科、属和种数的20．50％、10．72％和11．21％,包含蕨类植物2科2属2种、裸子植物1科1属1种、被子植物46科108属351种;其中,双子叶藤本种类具有明显优势,木质藤本数量多于草质藤本,优势科明显但单种属和寡种属数量较多。在生活型上以高位芽藤本种类为主,占总种数的80．80％,地下芽、一年生、地上芽和地面芽藤本种类较少,分别占总种数的6．21％、5．08％、4．52％和3．39％。在攀援方式上缠绕藤本具有明显优势,占总种数的46．61％;卷曲类、搭靠类和吸固类藤本种类较少,分别占总种数的24．58％、19．49％和9．32％。大部分藤本植物都具有2种以上的观赏特性,其中以观叶植物最多,占总种数的90．68％。繁育系统以两性花为主,单性花中雌雄异株种数多于雌雄同株,两性花、单性花和杂性花种类数分别占总种数的70．90％、27．69％和1．41％。分布区类型以热带成分为主,温带成分也占较大比例,说明该区域的藤本植物分布具有从热带成分向温带成分渗透和过渡的特性。调查结果表明：新宁野生藤本植物组成复杂、多样性特征明显,与该区域植物区系在中亚热带季风湿润气候条件下受山丘地貌区复杂生境长期作用有关。     

Making it transparent. On naming,framing and administrating biobank research on native people

Despite more than 50 years of genetic research on Sámi people in Sweden, there has been very little engagement with the ethical issues related to this research. My aim is to investigate the ethical challenges in biobank research on Sámi people, to identify ethical challenges that have been overlooked and to find ethical solutions. In my historical research inquiry of published material and interviews with people that have participated in this research, my research questions have been: How are blood samples from Sámi people collected, codified, governed and analyzed? What ethical strategies have been utilized? My main findings are: Sweden acquired biobank collections from Sámi people that are not registered or cannot be traced through the biobank register at the Swedish National Board of Health and Welfare. These collections entail ethical challenges concerning how the donors are identified, how the material is categorized, the regional ethical committees, governance and Sámi representation. My suggestions focus on transparency and traceability, competence and native peoples' rights and representation in biobank-related activities.     

Analysis of operating principles with S-system models

Operating principles address general questions regarding the response dynamics of biological systems as we observe or hypothesize them, in comparison to a priori equally valid alternatives. In analogy to design principles, the question arises: Why are some operating strategies encountered more frequently than others and in what sense might they be superior? It is at this point impossible to study operation principles in complete generality, but the work here discusses the important situation where a biological system must shift operation from its normal steady state to a new steady state. This situation is quite common and includes many stress responses. We present two distinct methods for determining different solutions to this task of achieving a new target steady state. Both methods utilize the property of S-system models within Biochemical Systems Theory (BST) that steady states can be explicitly represented as systems of linear algebraic equations. The first method uses matrix inversion, a pseudo-inverse, or regression to characterize the entire admissible solution space. Operations on the basis of the solution space permit modest alterations of the transients toward the target steady state. The second method uses standard or mixed integer linear programming to determine admissible solutions that satisfy criteria of functional effectiveness, which are specified beforehand. As an illustration, we use both methods to characterize alternative response patterns of yeast subjected to heat stress, and compare them with observations from the literature.     

Kinetics and thermodynamics of the rate-limiting conformational change in the actomyosin V mechanochemical cycle

We used FRET to examine the kinetics and thermodynamics of structural changes associated with ADP release in myosin V, which is thought to be a strain-sensitive step in many muscle and non-muscle myosins. We also explored essential dynamics using FIRST/FRODA starting with three different myosin V X-ray crystal structures to examine intrinsic flexibility and correlated motions. Our steady-state and time-resolved FRET analysis demonstrates a temperature-dependent reversible conformational change in the nucleotide-binding pocket (NBP). Our kinetic results demonstrate that the NBP goes from a closed to an open conformation prior to the release of ADP, while the actin-binding cleft remains closed. Interestingly, we find that the temperature dependence of the maximum actin-activated myosin V ATPase rate is similar to the pocket opening step, demonstrating that this is the rate-limiting structural transition in the ATPase cycle. Thermodynamic analysis demonstrates that the transition from the open to closed NBP conformation is unfavorable because of a decrease in entropy. The intrinsic flexibility analysis is consistent with conformational entropy playing a role in this transition as the MV.ADP structure is highly flexible compared to the MV.APO structure. Our experimental and modeling studies support the conclusion of a novel post-power-stroke actomyosin.ADP state in which the NBP and actin-binding cleft are closed. The novel state may be important for strain sensitivity as the transition from the closed to open NBP conformation may be altered by lever arm position.     

Modeling GPCR active state conformations: the β(2)-adrenergic receptor

The recent publication of several G protein-coupled receptor (GPCR) structures has increased the information available for homology modeling inactive class A GPCRs. Moreover, the opsin crystal structure shows some active features. We have therefore combined information from these two sources to generate an extensively validated model of the active conformation of the β(2)-adrenergic receptor. Experimental information on fully active GPCRs from zinc binding studies, site-directed spin labeling, and other spectroscopic techniques has been used in molecular dynamics simulations. The observed conformational changes reside mainly in transmembrane helix 6 (TM6), with additional small but significant changes in TM5 and TM7. The active model has been validated by manual docking and is in agreement with a large amount of experimental work, including site-directed mutagenesis information. Virtual screening experiments show that the models are selective for β-adrenergic agonists over other GPCR ligands, for (R)- over (S)-β-hydroxy agonists and for β(2)-selective agonists over β(1)-selective agonists. The virtual screens reproduce interactions similar to those generated by manual docking. The C-terminal peptide from a model of the stimulatory G protein, readily docks into the active model in a similar manner to which the C-terminal peptide from transducin, docks into opsin, as shown in a recent opsin crystal structure. This GPCR-G protein model has been used to explain site-directed mutagenesis data on activation. The agreement with experiment suggests a robust model of an active state of the β(2)-adrenergic receptor has been produced. The methodology used here should be transferable to modeling the active state of other GPCRs.     

TRAb在Graves病~(131)I治疗中的临床价值

目的:探讨促甲状腺激素受体抗体(TRAb)在Graves病131I治疗中的临床价值。方法:回顾性分析我院经131I治疗的186例Graves病患者,与70例健康对照组分别于131I治疗前及治疗后3、6、12和18月采用电化学发光免疫分析法(ECLA)动态检测血清TRAb、FT3、FT4、TSH浓度变化,进行统计分析,并计算TRAb的阳性率。结果:70例健康对照组TRAb水平1.09±0.45 IU/L,186例Graves病131I治疗前血清TRAb水平9.95±7.18 IU/L,明显高于健康对照组,两组比较有显著的统计学意义(t=-10.306,P0.001)。131I治疗3月后TRAb水平14.81±10.37 IU/L,明显高于治疗前(t=-5.26,P0.001);131I治疗6月后TRAb水平12.33±8.73 IU/L开始下降,治疗12月后TRAb水平3.14±0.87 IU/L明显降低;治疗18月后TRAb水平1.19±0.45 IU/L与健康对照组比较差异无统计学意义(t=-1.588,P=0.113)。Graves病131I治疗前TRAb阳性率为93.5%,治疗后3、6、12、18个月TRAb阳性率分别为93.5%、79.6%、27.4%和8.6%。结论:Graves病131I治疗中检测TRAb水平具有指导治疗、判断疗效、预测复发等重要的临床价值。     

Beyond average: an experimental test of temperature variability on the population dynamics of <Emphasis Type="Italic">Tribolium confusum</Emphasis>

The relationship between ectotherm ecology and climatic conditions has been mainly evaluated in terms of average conditions. Average temperature is the more common climatic variable used in physiological and population studies, and its effect on individual and population-level processes is well understood. However, the intrinsic variability of thermal conditions calls attention to the potential effects that this variability could have in ecological systems. Regarding this point, two hypotheses are proposed. From the allocation principle, it may be inferred that if temperature variability is high enough to induce stress in the organisms, then this extra-cost should reduce the energetic budget for reproduction, which will be reflected in population parameters. Moreover, a mathematical property of non-linear functions, Jensen’s inequality, indicates that, in concave functions, like the temperature–reproduction performance function, variability reduces the expected value of the output variable, and again modifies population parameters. To test these hypotheses, experimental cultures of Tribolium confusum under two different thermal variability regimens were carried out. With these data, we fitted a simple population dynamics model to evaluate the predictions of our hypothesis. The results show that thermal variability reduces the maximum reproductive rate of the population but no other parameters such as carrying capacity or the nonlinear factor in a nonlinear version of the Ricker model, which confirms our hypotheses. This result has important consequences, such as the paradoxical increase in population variability under a decrease in thermal variability and the necessary incorporation of climatic variability to evaluate the net effect of climate change on the dynamics of natural populations.     

白细胞介素23受体、白细胞介素17A在炎症性肠病患者中的表达及临床意义

目的：通过检测白细胞介素23受体（1L-23R）及白细胞介素17A（IL-17A）在炎症性肠病（IBD）患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义。方法：收集32例克罗恩病（CD）患者、29例溃疡性结肠炎（UC）患者及27例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-23R、IL-17AmRNA的表达情况,免疫组化技术分析IL-23R、IL-17A在肠黏膜中的原位表达。结果：与健康对照组相比,CD及UC患者肠黏膜组织内IL-23RmRNA表达显著增高（P〈0．05）,CD及UC组间的表达量差异无统计学意义（P〉0．05）。CD及UC患者肠黏膜组织内IL-17AmRNA表达显著增高（P〈0．05）,CD组肠黏膜组织内IL．17AmRNA表达显著高于uc组（P〈0．05）。免疫组化分析显示IL-23R阳性细胞在CD与uc肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-23R蛋白表达量最著增高（P〈0．05）,UC及CD组间的表达量差异无统计学意义（P〉0．05）。IL-17A阳性细胞在CD与UC肠黏膜固有层内有较多表达,较正常黏膜内的肠上皮细胞相比,CD及UC患者肠黏膜IL-17A蛋白表达量最著增高（P〈0．05）。结论：IL．23R及IL-17A在IBD患者肠黏膜中表达显著增高,提示IL-23R及IL-17A表达异常与IBD的发生发展密切相关,有可能成为IBD治疗的新靶点。