• 【比较六种诺达病毒的更大基因组片段及其编码的RNA复制。】 复制标题 收藏 收藏
    DOI:10.1099/0022-1317-82-8-1855 复制DOI
    作者列表:Johnson KN,Johnson KL,Dasgupta R,Gratsch T,Ball LA
    BACKGROUND & AIMS: :The Nodaviridae are a family of isometric RNA viruses that infect insects and fish. Their genomes, which are among the smallest known for animal viruses, consist of two co-encapsidated positive-sense RNA segments: RNA1 encodes the viral contribution to the RNA-dependent RNA polymerase (RdRp) which replicates the viral genome, whereas RNA2 encodes the capsid protein precursor. In this study, the RNA1 sequences of two insect nodaviruses - Nodamura virus (the prototype of the genus) and Boolarra virus - are reported as well as detailed comparisons of their encoded RdRps with those of three other nodaviruses of insects and one of fish. Although the 5' and 3' untranslated regions did not reveal common features of RNA sequence or secondary structure, these divergent viruses showed similar genome organizations and encoded RdRps that had from 26 to 99% amino acid sequence identity. All six RdRp amino acid sequences contained canonical RNA polymerase motifs in their C-terminal halves and conserved elements of predicted secondary structure throughout. A search for structural homologues in the protein structure database identified the poliovirus RdRp, 3D(pol), as the best template for homology modelling of the RNA polymerase domain of Pariacoto virus and allowed the construction of a congruent three-dimensional model. These results extend our understanding of the relationships among the RNA1 segments of nodaviruses and the predicted structures of their encoded RdRps.
    背景与目标: :Nodaviridae是感染昆虫和鱼类的等距RNA病毒家族。它们的基因组是动物病毒中已知最小的基因组,由两个共衣壳化的正义RNA片段组成:RNA1编码病毒对复制病毒基因组的RNA依赖性RNA聚合酶(RdRp)的贡献,而RNA2编码衣壳蛋白前体。在这项研究中,报道了两种昆虫诺达病毒RNA的序列-Nodamura病毒(属原型)和Boolarra病毒-以及它们编码的RdRps与其他三种昆虫和一种鱼类诺达病毒的RNA序列的详细比较。尽管5'和3'非翻译区未揭示RNA序列或二级结构的共同特征,但这些趋异病毒显示相似的基因组组织并编码具有26%至99%氨基酸序列同一性的RdRps。所有六个RdRp氨基酸序列在其C末端一半均包含规范的RNA聚合酶基序,并且在整个预测过程中均包含保守的二级结构元素。在蛋白质结构数据库中搜索结构同源物,发现脊髓灰质炎病毒RdRp,3D(pol)是对帕里亚科托病毒RNA聚合酶结构域进行同源建模的最佳模板,并可以构建全等的三维模型。这些结果扩展了我们对诺达病毒RNA1片段之间的关系及其编码的RdRps的预测结构的理解。
  • 【使用生物标记的糖消耗的流行病学评估:肥胖和非肥胖个体在欧洲诺福克癌症前瞻性研究中的比较。】 复制标题 收藏 收藏
    DOI:10.1158/1055-9965.EPI-06-1050 复制DOI
    作者列表:Bingham S,Luben R,Welch A,Tasevska N,Wareham N,Khaw KT
    BACKGROUND & AIMS: :We have previously shown that urinary sugars excretion in 24 h urine collections can serve as an independent biomarker of sugars consumption. In the European Prospective Investigation of Cancer (EPIC) Norfolk study of nutrition and cancer, this biomarker in spot urines has been assessed in a cross-sectional comparison of 404 obese individuals aged 45 to 75 years with a body mass index (BMI) of >30 kg/m(2) and 471 normal weight individuals aged 45 to 75 years with a BMI of <25 kg/m(2). In individuals of normal weight, sucrose, protein, and vitamin C intake were positively and highly significantly related to biomarkers in spot urine or plasma (P < 0.001), but there were no significant associations between biomarkers and food intake reports in the obese. Odds ratios for a BMI of >30 were significantly elevated for urinary sucrose [trend per milligram per liter quintile, 1.13; 95% confidence interval (95% CI), 1.02-1.25; P = 0.016], and the odds ratio for urinary sucrose/fructose ratio was highly significant (trend per quintile, 1.264; 95% CI, 1.142-1.401; P < 0.001). No associations for sugars intake and obesity were found using a food frequency questionnaire, and dietary vitamin C was apparently associated with increased risk (P < 0.001) despite an inverse association for plasma vitamin C. Nutritional biomarkers of consumption can complement existing methods for assessing cancer risk from diet in epidemiologic studies.
    背景与目标: :我们之前已经证明,24小时尿液收集物中尿糖的排泄可以作为糖消耗的独立生物标记。在欧洲癌症前瞻性研究(EPIC)对营养和癌症的诺福克研究中,通过对404名年龄在45至75岁,体重指数(BMI)> 30 kg / m(2)和471名体重正常的人,年龄在45至75岁之间,其BMI小于25 kg / m(2)。在体重正常的个体中,蔗糖,蛋白质和维生素C的摄入量与尿液或血浆中的生物标志物呈正相关且高度显着相关(P <0.001),但是在肥胖者中,生物标志物与食物摄入量之间没有显着相关性。尿蔗糖的BMI> 30的几率显着提高[每毫克每升五分位数的趋势为1.13; 95%置信区间(95%CI),1.02-1.25; P = 0.016],尿蔗糖/果糖比的优势比非常显着(每五分位数趋势为1.264; 95%CI为1.142-1.401; P <0.001)。使用食物频率问卷没有发现糖摄入和肥胖之间的关联,尽管血浆维生素C呈负相关,但饮食中维生素C显然与增加的风险相关(P <0.001)。食用营养生物标志物可以补充现有的评估癌症的方法流行病学研究中饮食带来的风险。
  • 【欧洲公众对食品风险的看法:跨国比较和方法比较。】 复制标题 收藏 收藏
    DOI:10.1111/j.1539-6924.2008.01021.x 复制DOI
    作者列表:Hohl K,Gaskell G
    BACKGROUND & AIMS: :This article presents a comparative study of public perceptions of food risk across 25 European member states. A secondary data analysis is conducted on a Eurobarometer survey fielded to nationally representative samples in 2005. The survey included closed questions as well as free associations to map risk perceptions. Taking a quantitative approach, we find that people in a majority of European countries express similar levels of concern about food risks. However, outside this majority a North-South divide is evident, with the Northern countries worrying less than the Southern countries. Multilevel modeling shows that cross-national differences in individual respondents' level of worry are in part attributable to shared country effects and to generalized risk sensitivity about a range of personal risks. On the underlying structure of food risk concerns, factor analysis points to three dimensions described by groupings of risks related to adulteration and contamination, health effects, and production and hygiene. A qualitative analysis of respondents' free associations about problems and risks with food identifies three major themes that are consistent with the quantitative results. However, the free associations also point toward greater cross-national diversity and to striking variations in the range and importance of food risks. Overall, the picture is of a public that frames food risks in a wider context of beliefs about the links between diet and health. We conclude with some implications for research on food risk perceptions in particular and risk perception studies in general.
    背景与目标: :本文对欧洲25个成员国的公众对食品风险的看法进行了比较研究。二次数据分析是在2005年对欧洲晴雨表进行的一次欧洲晴雨表调查中进行的,该调查针对的是全国代表性的样本。该调查包括封闭的问题以及建立风险感知图的免费协会。采用定量方法,我们发现大多数欧洲国家的人们对食品风险表达了相似的关注水平。但是,在多数之外,明显存在南北分歧,北方国家所担心的比南方国家要少。多级建模表明,各个受访者的担忧程度之间的跨国差异部分归因于共同的国家效应以及对一系列个人风险的普遍风险敏感性。关于食品风险关注的基本结构,因素分析指向三个维度,这些维度通过与掺假和污染,健康影响以及生产和卫生有关的风险分组来描述。对受访者关于食品问题和风险的自由联想的定性分析确定了与定量结果相一致的三个主要主题。但是,自由协会还指出了更大的跨国多样性,并指出了食品风险范围和重要性的显着差异。总体而言,该图描绘的是一个公众,其在关于饮食与健康之间的联系的更广泛的信念中描述了食物风险。我们得出结论,特别是对食品风险认知的研究和总体风险认知的研究。
  • 【全髋关节置换术中高度交联的聚乙烯与常规聚乙烯之间的设计特定比较结果。】 复制标题 收藏 收藏
    DOI:10.1080/17453674.2017.1307676 复制DOI
    作者列表:Johanson PE,Furnes O,Ivar Havelin L,Fenstad AM,Pedersen AB,Overgaard S,Garellick G,Mäkelä K,Kärrholm J
    BACKGROUND & AIMS: :Background and purpose - Most registry studies regarding highly crosslinked polyethylene (XLPE) have focused on the overall revision risk. We compared the risk of cup and/or liner revision for specific cup and liner designs made of either XLPE or conventional polyethylene (CPE), regarding revision for any reason and revision due to aseptic loosening and/or osteolysis. Patients and methods - Using the Nordic Arthroplasty Register Association (NARA) database, we identified cup and liner designs where either XLPE or CPE had been used in more than 500 THAs performed for primary hip osteoarthritis. We assessed risk of revision for any reason and for aseptic loosening using Cox regression adjusted for age, sex, femoral head material and size, surgical approach, stem fixation, and presence of hydroxyapatite coating (uncemented cups). Results - The CPE version of the ZCA cup had a risk of revision for any reason similar to that of the XLPE version (p = 0.09), but showed a 6-fold higher risk of revision for aseptic loosening (p < 0.001). The CPE version of the Reflection All Poly cup had an 8-fold elevated risk of revision for any reason (p < 0.001) and a 5-fold increased risk of revision for aseptic loosening (p < 0.001). The Charnley Elite Ogee/Marathon cup and the Trilogy cup did not show such differences. Interpretation - Whether XLPE has any advantage over CPE regarding revision risk may depend on the properties of the polyethylene materials being compared, as well as the respective cup designs, fixation type, and follow-up times. Further research is needed to elucidate how cup design factors interact with polyethylene type to affect the risk of revision.
    背景与目标: :背景和目的-大多数有关高度交联聚乙烯(XLPE)的注册研究都集中在总体修订风险上。我们比较了由XLPE或常规聚乙烯(CPE)制成的特定杯和内胆设计的杯和/或内胆翻新风险,无论是出于任何原因的翻新还是由于无菌松动和/或溶骨引起的翻新。患者和方法-使用北欧人工关节置换协会(NARA)数据库,我们确定了杯状和衬垫设计,其中XLPE或CPE在用于原发性髋骨关节炎的500多例THA中已经使用。我们使用因年龄,性别,股骨头材料和大小,手术方法,茎固定和羟基磷灰石涂层(无胶量杯)调整的Cox回归评估了由于任何原因和无菌性松动的翻修风险。结果-ZCA杯的CPE版本由于与XLPE版本类似的任何原因而具有翻修的风险(p = 0.09),但显示出无菌松动翻修的风险高6倍(p <0.001)。 CPE版本的Reflection All Poly杯由于任何原因翻新风险增加了8倍(p <0.001),而无菌松动翻新风险增加了5倍(p <0.001)。 Charnley Elite Ogee / Marathon杯和Trilogy杯未显示出此类差异。解释-XLPE在翻新风险方面是否比CPE有任何优势可能取决于所比较的聚乙烯材料的特性,以及相应的杯设计,固定类型和随访时间。需要进一步研究来阐明杯形设计因素如何与聚乙烯类型相互作用以影响翻新的风险。
  • 【与患有慢性疾病的老年妇女的心理健康相关的机制:年龄和疾病比较。】 复制标题 收藏 收藏
    DOI:10.1002/(SICI)1098-240X(199606)19:3<225::AID-NUR6> 复制DOI
    作者列表:Heidrich SM
    BACKGROUND & AIMS: The influence of type of illness (breast cancer versus osteoarthritis) and age on physical health and functioning, self-system interpretive mechanisms, and women's psychological well-being were examined. Self-system interpretive mechanisms are considered mediators of the effects of physical health on psychological well-being and include social comparisons, social integration, and illness perceptions. Young-old (aged 60-74) and old-old (75 +) women, diagnosed with osteoarthritis (N = 102) or breast cancer (N = 86), who volunteered for the study were interviewed using structured self-report scales. Young-old and old-old women did not differ in terms of health status, interpretive mechanisms, or on three of five indices of psychological well-being. On the other hand, women with arthritis, regardless of age, reported more functional health problems, more symptoms, and perceived their illness as more severe, more chronic, and less controllable than women with breast cancer. Although women with arthritis and breast cancer differed significantly in terms of physical health, they did not differ on multiple measures of psychological well-being. For both groups, women who made more positive social comparisons and who had more extensive social networks had higher levels of psychological well-being, regardless of physical health problems.

    背景与目标: 研究了疾病类型(乳腺癌与骨关节炎)和年龄对身体健康和功能,自我系统的解释机制以及女性心理健康的影响。自我系统的解释机制被认为是身体健康对心理健康的影响的中介者,包括社会比较,社会融合和疾病感知。自愿参加这项研究的年轻(年龄在60-74岁之间)和老年(75岁)妇女被诊断出患有骨关节炎(N = 102)或乳腺癌(N = 86),他们接受了结构化的自我报告量表的访问。男女老少在健康状况,解释机制或心理健康五个指标中的三个方面都没有差异。另一方面,与乳腺癌女性相比,患有关节炎的女性,无论年龄大小,都报告了更多的功能性健康问题,更多的症状,并且认为自己的疾病更严重,更慢性,更难控制。尽管患有关节炎和乳腺癌的妇女在身体健康方面存在显着差异,但在心理健康的多种衡量指标上并没有差异。对于这两个群体,无论身体健康问题如何,进行更积极的社会比较并拥有更广泛的社交网络的女性都有较高的心理健康水平。

  • 【骨骼肌的兴奋收缩耦合:与心肌的比较。】 复制标题 收藏 收藏
    DOI:10.1046/j.1440-1681.2000.03224.x 复制DOI
    作者列表:Lamb GD
    BACKGROUND & AIMS: :1. The present review describes the mechanisms involved in controlling Ca2+ release from the sarcoplasmic reticulum (SR) of skeletal muscle, which ultimately regulates contraction. 2. Comparisons are made between cardiac and skeletal muscle with respect to: (i) the role of the dihydropyridine receptors (DHPR) as Ca2+ channels and voltage-sensors; (ii) the regulation of the ryanodine receptor (RyR)/Ca2+-release channels in the SR; and (iii) the importance of Ca2+-induced Ca2+ release. 3. It is shown that the key differences of the skeletal muscle Ca2+-release channel (RyR1), namely the increase in its stimulation by ATP and its inhibition by Mg2+, are critical for its direct regulation by the associated DHPR and, consequently, for the fast, accurate control of skeletal muscle contraction.
    背景与目标: :1。本综述描述了控制Ca2从骨骼肌的肌浆网(SR)释放的机制,该机制最终调节了收缩。 2.在心肌和骨骼肌之间进行以下方面的比较:(i)二氢吡啶受体(DHPR)作为Ca2通道和电压传感器的作用; (ii)调节SR中的ryanodine受体(RyR)/ Ca2释放通道; (iii)Ca2诱导的Ca2释放的重要性。 3.研究表明,骨骼肌Ca2释放通道(RyR1)的关键差异,即ATP对其刺激的增加和Mg2对其的抑制,对于直接由相关的DHPR调节至关重要,因此对于快速,准确地控制骨骼肌收缩。
  • 【身体健壮和膝盖以下截肢的儿童在行走过程中的外部负荷比较。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Engsberg JR,Lee AG,Patterson JL,Harder JA
    BACKGROUND & AIMS: :The purpose of this investigation was to determine external loading variables that could describe any statistically significant differences between the limbs of below-knee-amputee (BKA) and able-bodied children. Eleven able-bodied children and four BKA children volunteered to participate in this investigation. Force platform data were collected for two consecutive foot falls during two experimental sessions. Significant external load differences existed between the prosthetic limbs and nonprosthetic limbs of BKA children and between limbs of the BKA and able-bodied children. The prosthetic limb generally displayed a subordinate role when compared to nonprosthetic and normal limbs. The nonprosthetic limbs displayed a dominant role when compared to the other limbs. These external loading characteristics of the prosthetic and nonprosthetic limbs may be a logical consequence of the morphologic and functional differences that exist between the groups. It was concluded that as long as the prosthetic limb functions differently from a normal limb, BKA children may have a difficult time walking the same as able-bodied children. It would appear to be advantageous to determine the most appropriate gait pattern for BKA children, given the influence of such factors as prosthetic design, construction, and alignment, rehabilitation, and joint loading.
    背景与目标: :这项研究的目的是确定外部负荷变量,这些变量可以描述膝盖以下截肢者(BKA)和肢体健全的孩子四肢之间的任何统计学上的显着差异。 11名身体健全的儿童和4名BKA儿童自愿参加了这项调查。在两个实验阶段连续两次跌倒时,收集了部队平台数据。 BKA儿童的假肢和非假肢之间以及BKA的肢体和身体健全的孩子之间存在显着的外部负荷差异。与非假肢和正常肢相比,假肢通常表现出从属作用。与其他肢体相比,非假肢肢体表现出主导作用。假肢和非假肢的这些外部负荷特征可能是两组之间存在形态和功能差异的逻辑结果。结论是,只要假肢的功能与正常肢体不同,BKA儿童与健壮儿童的行走时间可能会很困难。考虑到假体设计,构造,对准,康复和关节负荷等因素的影响,为BKA儿童确定最合适的步态模式似乎是有利的。
  • 【在进行间接比较时使用meta回归:将依西酞普兰与文拉法辛XR进行比较。】 复制标题 收藏 收藏
    DOI:10.1185/030079906X148625 复制DOI
    作者列表:Eckert L,Falissard B
    BACKGROUND & AIMS: BACKGROUND:In the absence of well-powered, randomised, direct-comparison trials, indirect comparisons are the only option for comparing treatment strategies. Several methodologies have been developed and each has sparked criticism. Using direct comparisons of escitalopram versus venlafaxine extended release (XR), we explore the differences between the two compounds through indirect comparisons. METHODS:The CENTRAL, Medline and Embase databases were interrogated, focusing on randomized placebo-controlled clinical trials involving adult patients treated for major depressive disorder in the acute phase. Corresponding authors were contacted to reduce missing data. Effect sizes were derived from each study's primary outcome. For indirect comparisons, a global effect size was computed through meta-regression. For direct comparisons, the studies were considered separately due to missing data. Non-inferiority assessments were employed. The conclusion of the meta-regression was then compared with the conclusions made in direct comparison trials. RESULTS:Ten placebo-controlled studies--six assessing escitalopram and four assessing venlafaxine XR--and two direct comparison studies were retrieved. Escitalopram was found to be non-inferior to venlafaxine XR in both indirect and direct comparisons with results of mean -0.02 (unilateral 95% confidence interval [CI] -0.16 to infinity) and 0.23 (95% CI -0.01 to infinity), respectively. Results obtained by both indirect and direct comparisons were similar. Investigating the influence of age, gender repartition and severity at baseline suggests that results are consistent. Results were also considered robust against publication bias. CONCLUSIONS:This empirical finding suggests that escitalopram is non-inferior to venlafaxine XR. This reinforces the evidence found in direct comparisons trials. Indirect comparisons through meta-regression may be suitable to support decision-making. To fully assess its potential, further evaluation of this methodology, using other examples, is needed.
    背景与目标: 背景:在缺乏功能强大,随机,直接比较试验的情况下,间接比较是比较治疗策略的唯一选择。已经开发了几种方法,每种方法都引发了批评。使用艾司西酞普兰与文拉法辛缓释(XR)的直接比较,我们通过间接比较探索了两种化合物之间的差异。
    方法:对CENTRAL,Medline和Embase数据库进行了调查,重点是随机对照安慰剂对照的临床试验,该试验涉及在急性期接受过重度抑郁症治疗的成年患者。与通讯作者联系以减少丢失的数据。效果大小来自每项研究的主要结果。对于间接比较,通过meta回归计算全局效应大小。对于直接比较,由于缺少数据,将研究单独考虑。采用非自卑性评估。然后将荟萃回归的结论与直接比较试验中得出的结论进行比较。
    结果:十项安慰剂对照研究-六项评估艾司西酞普兰和四项评估文拉法辛XR-并检索到两项直接比较研究。在间接和直接比较中,依西酞普兰均不低于文拉法辛XR,均值分别为-0.02(单边95%置信区间[CI] -0.16至无穷大)和0.23(95%CI -0.01至无穷大)。 。通过间接和直接比较获得的结果相似。在基线时调查年龄,性别划分和严重程度的影响表明结果是一致的。结果也被认为对发表偏见是有力的。
    结论:该经验发现表明艾司西酞普兰不逊于文拉法辛XR。这加强了直接比较试验中发现的证据。通过元回归进行的间接比较可能适合于支持决策。为了充分评估其潜力,需要使用其他示例对这种方法进行进一步评估。
  • 【序列基序比较从木瓜环斑杯状病毒建立了多功能蛋白质HC-Pro的功能图。】 复制标题 收藏 收藏
    DOI:10.1007/BF03263287 复制DOI
    作者列表:Mangrauthia SK,Jain RK,Praveen S
    BACKGROUND & AIMS: :Helper component proteinase (HC-Pro) is a multifunctional protein responsible for multiple molecular events in viral cycle. Here, we demonstrate that functional correlation of sequence motifs of HC-Pro is an important source to predict its role in deubiqutinylation pathway and rescuing viral proteins from degradation. The sequence of papaya ringspot viral HC-Pro was compared with respect to both inter and intea-species across different potyviruses. This study suggested that highly conserved domains involved in post transcriptional gene silencing (PTGS) suppression and proteolytic activity are essential functions in plant-virus cycle. In contrast, mechanisms primed for differentiation such as host specificity and virus replication are less conserved. Also, they contribute substantially to the differences among HC-Pro, derived from different potyviruses. The results obtained from this study provide a framework for new hypothesis and research directions in the area of differential role of potyviral HC-Pro.
    背景与目标: :Helper组分蛋白酶(HC-Pro)是一种多功能蛋白,负责病毒周期中的多个分子事件。在这里,我们证明了HC-Pro序列基序的功能相关性是预测其在去泛素化途径中的作用以及从降解中拯救病毒蛋白的重要来源。比较了木瓜环斑病毒HC-Pro的序列,它们涉及跨不同马铃薯病毒的种间和种间。这项研究表明,参与转录后基因沉默(PTGS)抑制和蛋白水解活性的高度保守的域是植物-病毒循环中必不可少的功能。相反,用于分化的机制,例如宿主特异性和病毒复制,则保守性较低。同样,它们也极大地促进了源自不同马铃薯病毒的HC-Pro之间的差异。从这项研究中获得的结果为在杯状病毒HC-Pro的不同作用领域提供了新的假设和研究方向的框架。
  • 【比较AD LIBITUM和为断奶后增重而选择和未选择的小鼠的限制性喂养。二。体组成和能量效率。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Timon VM,Eisen EJ,Leatherwood JM
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【Ppara基因敲除和siRNA基因敲除小鼠的转录和表型比较。】 复制标题 收藏 收藏
    DOI:10.1093/nar/gkl609 复制DOI
    作者列表:De Souza AT,Dai X,Spencer AG,Reppen T,Menzie A,Roesch PL,He Y,Caguyong MJ,Bloomer S,Herweijer H,Wolff JA,Hagstrom JE,Lewis DL,Linsley PS,Ulrich RG
    BACKGROUND & AIMS: :RNA interference (RNAi) has great potential as a tool for studying gene function in mammals. However, the specificity and magnitude of the in vivo response to RNAi remains to be fully characterized. A molecular and phenotypic comparison of a genetic knockout mouse and the corresponding knockdown version would help clarify the utility of the RNAi approach. Here, we used hydrodynamic delivery of small interfering RNA (siRNA) to knockdown peroxisome proliferator activated receptor alpha (Ppara), a gene that is central to the regulation of fatty acid metabolism. We found that Ppara knockdown in the liver results in a transcript profile and metabolic phenotype that is comparable to those of Ppara-/- mice. Combining the profiles from mice treated with the PPARalpha agonist fenofibrate, we confirmed the specificity of the RNAi response and identified candidate genes proximal to PPARalpha regulation. Ppara knockdown animals developed hypoglycemia and hypertriglyceridemia, phenotypes observed in Ppara-/- mice. In contrast to Ppara-/- mice, fasting was not required to uncover these phenotypes. Together, these data validate the utility of the RNAi approach and suggest that siRNA can be used as a complement to classical knockout technology in gene function studies.
    背景与目标: RNA干扰(RNAi)作为研究哺乳动物基因功能的工具具有巨大潜力。但是,体内对RNAi应答的特异性和强度仍有待充分表征。基因敲除小鼠和相应的敲除版本的分子和表型比较将有助于阐明RNAi方法的实用性。在这里,我们利用小分子干扰RNA(siRNA)的流体动力学传递来敲低过氧化物酶体增殖物激活的受体α(Ppara),该基因是调节脂肪酸代谢的关键基因。我们发现肝脏中的Ppara敲低导致与Ppara-/-小鼠的转录谱和代谢表型相当。结合使用PPARalpha激动剂非诺贝特治疗的小鼠的概况,我们确认了RNAi反应的特异性,并确定了与PPARalpha调节最接近的候选基因。 Ppara基因敲低动物出现低血糖和高甘油三酯血症,这是在Ppara-/-小鼠中观察到的表型。与Ppara-/-小鼠相反,不需要禁食即可发现这些表型。总之,这些数据验证了RNAi方法的实用性,并表明siRNA可以用作基因功能研究中经典敲除技术的补充。
  • 【化学作图和与同能寡核苷酸微阵列结合之间的比较揭示了与枯草芽孢杆菌RNase P RNA特异性结构域结合的意外模式。】 复制标题 收藏 收藏
    DOI:10.1021/bi100286n 复制DOI
    作者列表:Liang R,Kierzek E,Kierzek R,Turner DH
    BACKGROUND & AIMS: :Microarrays with isoenergetic pentamer and hexamer 2'-O-methyl oligonucleotide probes with LNA (locked nucleic acid) and 2,6-diaminopurine substitutions were used to probe the binding sites on the RNase P RNA specificity domain of Bacillus subtilis. Unexpected binding patterns were revealed. Because of their enhanced binding free energies, isoenergetic probes can break short duplexes, merge adjacent loops, and/or induce refolding. This suggests new approaches to the rational design of short oligonucleotide therapeutics but limits the utility of microarrays for providing constraints for RNA structure determination. The microarray results are compared to results from chemical mapping experiments, which do provide constraints. Results from both types of experiments indicate that the RNase P RNA folds similarly in 1 M Na(+) and 10 mM Mg(2+).
    背景与目标: :使用具有等能量五聚体和具有LNA(锁定核酸)和2,6-二氨基嘌呤取代的六聚体2'-O-甲基寡核苷酸探针的微阵列来探测枯草芽孢杆菌RNase P RNA特异性结构域上的结合位点。揭示了意外的绑定模式。由于其增强的结合自由能,等能探针可以破坏短双链体,合并相邻环和/或诱导重折叠。这提示了合理设计短寡核苷酸疗法的新方法,但限制了微阵列为RNA结构测定提供限制的实用性。将微阵列结果与来自化学作图实验的结果进行比较,这确实提供了限制。两种实验的结果均表明,RNase P RNA在1 M Na()和10 mM Mg(2)中折叠相似。
  • 【末端执行器和外骨骼康复机器人在中度至重度上肢功能不全的慢性卒中患者上肢功能方面的比较。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-020-58630-2 复制DOI
    作者列表:Lee SH,Park G,Cho DY,Kim HY,Lee JY,Kim S,Park SB,Shin JH
    BACKGROUND & AIMS: :End-effector (EE) and exoskeleton (Exo) robots have not been directly compared previously. The present study aimed to directly compare EE and Exo robots in chronic stroke patients with moderate-to-severe upper limb impairment. This single-blinded, randomised controlled trial included 38 patients with stroke who were admitted to the rehabilitation hospital. The patients were equally divided into EE and Exo groups. Baseline characteristics, including sex, age, stroke type, brain lesion side (left/right), stroke duration, Fugl-Meyer Assessment (FMA)-Upper Extremity score, and Wolf Motor Function Test (WMFT) score, were assessed. Additionally, impairment level (FMA, motor status score), activity (WMFT), and participation (stroke impact scale [SIS]) were evaluated. There were no significant differences in baseline characteristics between the groups. After the intervention, improvements were significantly better in the EE group with regard to activity and participation (WMFT-Functional ability rating scale, WMFT-Time, and SIS-Participation). There was no intervention-related adverse event. The EE robot intervention is better than the Exo robot intervention with regard to activity and participation among chronic stroke patients with moderate-to-severe upper limb impairment. Further research is needed to confirm this novel finding.
    背景与目标: :之前尚未直接比较末端执行器(EE)和外骨骼(Exo)机器人。本研究旨在直接比较中度至重度上肢损伤的慢性卒中患者的EE和Exo机器人。这项单盲,随机对照试验包括38例中风患者,他们均入了康复医院。将患者平均分为EE组和Exo组。评估了基线特征,包括性别,年龄,中风类型,脑病变侧(左/右),中风持续时间,Fugl-Meyer评估(FMA)-上肢得分和狼运动功能测试(WMFT)得分。此外,还评估了损伤水平(FMA,运动状态评分),活动(WMFT)和参与(中风影响量表[SIS])。两组之间的基线特征无显着差异。干预后,EE组在活动和参与(WMFT功能能力等级量表,WMFT时间和SIS参与)方面的改善明显更好。没有干预相关的不良事件。就中度至重度上肢功能障碍的慢性卒中患者的活动和参与程度而言,EE机器人干预优于Exo机器人干预。需要进一步的研究来证实这一新发现。
  • 【小鼠和人类前白蛋白之间的结构比较。】 复制标题 收藏 收藏
    DOI:10.1093/oxfordjournals.jbchem.a135442 复制DOI
    作者列表:Wakasugi S,Maeda S,Shimada K,Nakashima H,Migita S
    BACKGROUND & AIMS: :In an attempt to construct model systems for familial amyloidotic polyneuropathy, prealbumin cDNA was cloned from a mouse liver cDNA library, using previously cloned human prealbumin cDNA as a hybridization probe. The primary structure of mouse prealbumin deduced from the cDNA sequence shows that it consists of 147 amino acids, including a whole prealbumin sequence (127 amino acids) and a putative signal sequence (20 amino acids). These numbers are in complete agreement with those determined for the human prealbumin. Among the 127 amino acid residues of the mature human prealbumin, 25 are replaced by different amino acids in the mouse prealbumin. Interestingly, 24 out of the 25 substituted amino acids are located at the outer surface of the protein, and the regions corresponding to the core and central channel of the protein are almost completely conserved. The cloned cDNA provided essential information for manipulating amyloidosis in mice.
    背景与目标: :为构建家族性淀粉样变性多发性神经病的模型系统,使用先前克隆的人前白蛋白cDNA作为杂交探针,从小鼠肝脏cDNA文库中克隆了前白蛋白cDNA。从cDNA序列推导的小鼠前白蛋白的一级结构显示,它由147个氨基酸组成,包括一个完整的前白蛋白序列(127个氨基酸)和一个假定的信号序列(20个氨基酸)。这些数字与为人白蛋白测定的数字完全一致。成熟的人前白蛋白的127个氨基酸残基中,有25个被小鼠前白蛋白中的不同氨基酸取代。有趣的是,在25个取代氨基酸中,有24个位于蛋白质的外表面,并且对应于蛋白质核心和中央通道的区域几乎完全保守。克隆的cDNA为操纵小鼠淀粉样变性提供了重要信息。
  • 【各种心理社会疗法对抑郁症儿童和青少年的有效性比较:贝叶斯网络荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1007/s00787-020-01492-w 复制DOI
    作者列表:Liang JH,Li J,Wu RK,Li JY,Qian S,Jia RX,Wang YQ,Qian YX,Xu Y
    BACKGROUND & AIMS: :The existence of depression among children or adolescents can trigger a sequence of burdens on themselves, their families and even the whole society, which cause both physical and economic impacts. Our network meta-analysis (NMA) was aimed at comparing them with each other for evaluating the optimal psychosocial therapy to help children and adolescents with depression to improve their mental health. Based on several biomedical databases, a system of search strategies was conducted for searching randomized controlled trials (RCTs) which published from their inception on October, 1st 2018 without language restriction. We carried out an expression analysis for comparing the efficacy of various psychosocial therapies using Bayesian NMA. A battery of analyses and assessments, such as conventional meta-analysis and risk of bias, were performed concurrently. Only 32 of RCTs which involved 2677 participants were eventually included in our analyses from the 19,176 of initial citation screening. In addition, in terms of various valid assessment instruments, interpersonal psychotherapy [standard mean difference (SMD) = -1.38, Credible interval (CrI) - 2.5, - 0.20)], computer cognitive-behavioral therapy (SMD = -1.36, CrI - 2.59, - 0.14), cognitive-behavioral therapy (SMD = -1.16, CrI - 2.15, - 0.18), had significantly better effects than the named control group. All together, these results suggest that interpersonal psychotherapy might be the best approach to improve the depressive state among children and adolescents. This study may provide an excellent resource for future endeavors to utilize psychosocial interventions and may also serve as a springboard for creative undertakings as yet unknown.
    背景与目标: :儿童或青少年抑郁症的存在会给自己,家庭乃至整个社会带来一系列负担,从而造成身体和经济上的双重影响。我们的网络荟萃分析(NMA)旨在将它们彼此进行比较,以评估最佳的心理治疗方法,以帮助患有抑郁症的儿童和青少年改善其心理健康。基于几个生物医学数据库,实施了一个搜索策略系统以搜索随机对照试验(RCT),该试验于2018年10月1日开始发布,没有语言限制。我们进行了表达分析,以比较使用贝叶斯NMA进行的各种心理社会疗法的疗效。同时进行了一系列分析和评估,例如常规的荟萃分析和偏倚风险。从19,176例首次引文筛选中,最终只有32篇RCT(涉及2677名参与者)被纳入我们的分析。此外,就各种有效的评估工具而言,人际心理治疗[标准平均差异(SMD)= -1.38,可信区间(CrI)-2.5,-0.20)],计算机认知行为疗法(SMD = -1.36,CrI- 2.59,-0.14),认知行为疗法(SMD = -1.16,CrI-2.15,-0.18)效果明显优于对照组。总之,这些结果表明,人际心理治疗可能是改善儿童和青少年抑郁状态的最佳方法。这项研究可以为将来利用社会心理干预的努力提供极好的资源,并且还可以作为尚不为人所知的创造性事业的跳板。

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