• 【在流感血凝素的相同抗原位点具有特异性的辅助T细胞之间存在很大程度的功能多样性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Haberman AM,Moller C,McCreedy D,Gerhard WU
    BACKGROUND & AIMS: :The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes.
    背景与目标: 流感病毒血凝素分子(A / PR / 8/34)的1位点决定簇是BALB / c Th细胞对Ha的免疫应答中的几个免疫优势位点之一。包含该T细胞位点的合成肽(HA110-120),在该决定簇中包含单个取代基的一组类似物以及在氨基或羧基端截短的同源物用于检查15个对该位点特异性的T细胞的精细特异性在I-Ed中为-1。结果表明,最小决定簇内的每个残基都在T细胞识别过程中起作用,因为这些位置中任何一个的单取代都会影响肽刺激至少一些位点1特异性T细胞的能力。对于所检查的大多数残基,取代对不同的T细胞的影响不同,表明取代的残基以受体特异性方式影响识别。检查的15个T细胞中的每一个都有独特的精细特异性模式,表明该位点的BALB / c T细胞库可能超过100种不同的克隆型。
  • 【功能性精子发生的发展需要生殖细胞凋亡的早期和大规模。】 复制标题 收藏 收藏
    DOI:10.1093/emboj/16.9.2262 复制DOI
    作者列表:Rodriguez I,Ody C,Araki K,Garcia I,Vassalli P
    BACKGROUND & AIMS: Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.

    背景与目标: 在雄性生殖细胞中表达高水平BclxL或Bcl2蛋白的转基因小鼠表现出高度异常的成年精子发生并伴有不育。这似乎是由于防止了睾丸早期大量凋亡的结果,这种情况发生在第一轮精子发生过程中的生发细胞之间。相反,在成年转基因小鼠中,不能阻止正常成年人睾丸中发生的精原细胞中的偶发性细胞凋亡。睾丸中的生理性早期凋亡波在时间和位置上是一致的,具有促凋亡的蛋白Bax的临时高表达,该蛋白在性成熟时消失。 BclxL和Bax蛋白的细胞内平衡(可能是激素控制的)(在正常小鼠的睾丸中显然不表达Bcl2)在细胞内平衡中起着至关重要的作用,这是通过在小鼠体内出现类似的睾丸综合症而证明的。 bax基因。凋亡波似乎是正常成熟精子发生发展所必需的,这可能是因为它在某些生细胞阶段和支持细胞之间维持了关键的细胞数比,其正常功能和分化牵涉到复杂的交流网络。

  • 【不同类型的刺激对兔颈总动脉中环AMP含量的影响:功能意义。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.1990.tb03137.x 复制DOI
    作者列表:Pérez-García MT,Almaraz L,González C
    BACKGROUND & AIMS: :Cyclic AMP levels in rabbit carotid bodies incubated under control conditions, 100% O2- or 95% O2/5% CO2- equilibrated medium, are close to 1 pmol/mg wet tissue (range 0.4-2.43 pmol/mg). Isobutylmethylxanthine (0.5 mM) increases cyclic AMP levels by a factor of 14 and 8 in HEPES- and CO2/CH3O(-)-buffered medium, respectively. Forskolin (0.5-10 microM) applied during 30 min increases cyclic AMP levels in a dose-dependent manner. Incubation of carotid bodies at low O2 tensions resulted in an elevation of cyclic AMP levels both in the absence and in the presence of isobutymethylxanthine. In the latter conditions cyclic AMP increase was maximum at an O2 tension of 46 mm Hg and tended to decrease at extremely low PO2. In isobutylmethylxanthine-containing Ca2(+)-free medium, cyclic AMP increased linearly with decreasing PO2 from 66 to 13 mm Hg; the absolute cyclic AMP levels attained in Ca2(+)-free medium were smaller than those observed in Ca2(+)-containing medium at any PO2. The differences between Ca2(+)-free and Ca2(+)-containing media appear to be due to the action of released neurotransmitters in the latter conditions, because dopamine and norepinephrine, which are known to be released by hypoxia in a Ca2(+)-dependent manner, increase cyclic AMP in the carotid body. Low pH/high PCO2 and high [K+]e increase cyclic AMP levels only in Ca2(+)-containing medium. Forskolin potentiates the release of catecholamines induced by low PO2. These results suggest that cyclic AMP plays an important role in the modulation of the chemoreception process.
    背景与目标: :在对照条件下,100%O2-或95%O2 / 5%CO2平衡的培养基中孵育的兔颈动脉体中的循环AMP水平接近1 pmol / mg湿组织(0.4-2.43 pmol / mg范围)。在HEPES-和CO2 / CH3O(-)缓冲的培养基中,异丁基甲基黄嘌呤(0.5 mM)将循环AMP的水平分别提高14和8倍。在30分钟内施用的Forskolin(0.5-10 microM)以剂量依赖性方式增加循环AMP的水平。在不存在和存在异丁甲基黄嘌呤的情况下,在低O2张力下孵育颈动脉都会导致环AMP含量升高。在后一种情况下,循环AMP的增加在O2张力为46 mm Hg时最大,而在极低的PO2下趋于减少。在不含异丁基甲基黄嘌呤的不含Ca2()的介质中,环状AMP随着PO2从66 mmHg降低到13 mm Hg而线性增加。不含Ca2()的培养基中获得的绝对循环AMP水平要小于任何PO2含Ca2()的培养基中观察到的绝对值。不含Ca2()和含Ca2()的培养基之间的差异似乎是由于后者条件下释放的神经递质的作用所致,因为已知多巴胺和去甲肾上腺素在依赖Ca2()的低氧状态下会释放方式,增加颈动脉体中的循环AMP。低pH /高PCO2和高[K] e仅在含Ca2()的培养基中会增加循环AMP的水平。 Forskolin增强了低PO2诱导的儿茶酚胺释放。这些结果表明,环状AMP在化学感受过程的调节中起重要作用。
  • 【遗传变异的多种类型集中在精神分裂症所涉及的功能基因网络上。】 复制标题 收藏 收藏
    DOI:10.1038/nn.3261 复制DOI
    作者列表:Gilman SR,Chang J,Xu B,Bawa TS,Gogos JA,Karayiorgou M,Vitkup D
    BACKGROUND & AIMS: :Despite the successful identification of several relevant genomic loci, the underlying molecular mechanisms of schizophrenia remain largely unclear. We developed a computational approach (NETBAG+) that allows an integrated analysis of diverse disease-related genetic data using a unified statistical framework. The application of this approach to schizophrenia-associated genetic variations, obtained using unbiased whole-genome methods, allowed us to identify several cohesive gene networks related to axon guidance, neuronal cell mobility, synaptic function and chromosomal remodeling. The genes forming the networks are highly expressed in the brain, with higher brain expression during prenatal development. The identified networks are functionally related to genes previously implicated in schizophrenia, autism and intellectual disability. A comparative analysis of copy number variants associated with autism and schizophrenia suggests that although the molecular networks implicated in these distinct disorders may be related, the mutations associated with each disease are likely to lead, at least on average, to different functional consequences.
    背景与目标: :尽管成功鉴定了几个相关的基因组位点,但精神分裂症的潜在分子机制仍不清楚。我们开发了一种计算方法(NETBAG),该方法可以使用统一的统计框架对与疾病相关的多种遗传数据进行综合分析。这种方法在使用无偏态全基因组方法获得的精神分裂症相关遗传变异中的应用,使我们能够鉴定出与轴突导向,神经元细胞移动性,突触功能和染色体重塑有关的几个内聚基因网络。形成网络的基因在大脑中高度表达,在产前发育过程中大脑表达更高。所确定的网络在功能上与先前与精神分裂症,自闭症和智力障碍有关的基因有关。对与自闭症和精神分裂症有关的拷贝数变异的比较分析表明,尽管与这些独特疾病有关的分子网络可能是相关的,但与每种疾病有关的突变可能至少平均而言导致不同的功能后果。
  • 【患有ASD的幼儿的小脑内连接性和体感反应性。】 复制标题 收藏 收藏
    DOI:10.1186/s13229-017-0143-y 复制DOI
    作者列表:Failla MD,Peters BR,Karbasforoushan H,Foss-Feig JH,Schauder KB,Heflin BH,Cascio CJ
    BACKGROUND & AIMS: BACKGROUND:The human somatosensory system comprises dissociable paths for discriminative and affective touch, reflected in separate peripheral afferent populations and distinct cortical targets. Differences in behavioral and neural responses to affective touch may have an important developmental role in early social experiences, which are relevant for autism spectrum disorder (ASD). METHODS:Using probabilistic tractography, we compared the structural integrity of white matter pathways for discriminative and affective touch in young children with ASD and their typically developing (TD) peers. We examined two tracts: (1) a tract linking the thalamus with the primary somatosensory cortex, which carries discriminative tactile information, and (2) a tract linking the posterior insula-the cortical projection target of unmyelinated tactile afferents mediating affective touch-with the anterior insula, which integrates sensory and visceral inputs to interpret emotional salience of sensory stimuli. We investigated associations between tract integrity and performance on a standardized observational assessment measuring tactile discrimination and affective responses to touch. RESULTS:Both the thalamocortical and intrainsular tracts showed reduced integrity (higher mean diffusivity) in the ASD group compared to those in the TD group. Consistent with the previous findings, the ASD group exhibited impaired tactile discriminative ability, more tactile defensiveness, and more sensory seeking (e.g., enthusiastic play or repetitive engagement with a specific tactile stimulus). There was a significant relation between intrainsular tract integrity and tactile seeking. The direction of this relation differed between groups: higher intrainsular mean diffusivity (MD) (reflecting decreased tract integrity) was associated with increased tactile seeking in the TD group but with decreased tactile seeking in the ASD group. In the TD group, decreased tactile defensiveness was also associated with higher intrainsular MD, but there was no relation in the ASD group. Discriminative touch was not significantly associated with integrity of either tract in either group. CONCLUSIONS:These results support previous findings suggesting a central role for the insula in affective response to touch. While both discriminative and affective touch and both somatosensory tracts are affected in ASD, the restriction of brain-behavior associations to the intrainsular tract and tactile seeking suggests more complex and perhaps higher-order influence on differences in tactile defensiveness and discrimination.
    背景与目标: 背景:人体体感系统包括区分性和情感性接触的可分离路径,分别反映在不同的周围传入群体和不同的皮层目标中。情感接触的行为和神经反应差异可能在早期的社会经历中具有重要的发展作用,这与自闭症谱系障碍(ASD)有关。
    方法:我们使用概率束摄影术,比较了ASD幼儿和典型的发展中(TD)同伴的辨别性和情感性触觉的白质通路的结构完整性。我们检查了两个通道:(1)将丘脑与初级体感皮层相连的通道,该通道带有可分辨的触觉信息;(2)将后岛绝缘体(未髓鞘的触觉传入的皮层投射目标与介导情感接触的皮层投射目标)相连接的通道。前岛绝缘,整合了感觉和内脏的输入,以解释感觉刺激的显着性。在标准的观察评估中,我们研究了管道完整性与性能之间的关联,该评估评估了触觉歧视和对触摸的情感反应。
    结果:与TD组相比,ASD组的丘脑皮质和脑内束道均显示完整性降低(平均扩散率更高)。与之前的发现一致,ASD组表现出触觉辨别能力受损,触觉防御能力增强和寻求更多感官感受(例如,对特定触觉刺激的热情玩耍或反复参与)。道内完整性与触觉寻求之间存在显着的关系。各组之间的这种关系的方向是不同的:TD组的较高的趾内平均扩散度(MD)(反映了管道完整性的降低)与触觉的增加相关,而ASD组的触觉的下降相关。在TD组中,触觉防御力下降也与较高的总动脉内MD有关,但在ASD组中则没有关系。辨别性触觉与两组中任何一条道的完整性均无显着相关性。
    结论:这些结果支持以前的发现,表明绝缘体在触摸的情感反应中起着核心作用。尽管区分性和情感性接触以及体感束都受到ASD的影响,但脑行为关联对束缚束和触觉的限制表明对触觉防御和辨别力差异的影响可能更为复杂,甚至可能更高。
  • 【健康人类中与年龄相关的皮质兴奋性和连接性变化:通过TMS-EEG对感觉运动网络的非侵入性评估。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2017.06.014 复制DOI
    作者列表:Ferreri F,Guerra A,Vollero L,Ponzo D,Maatta S,Mervaala E,Iannello G,Di Lazzaro V
    BACKGROUND & AIMS: :The sensorimotor cortical system undergoes structural and functional changes across its lifespan. Some of these changes are physiological and parallel the normal aging process, while others might represent pathophysiological mechanisms underlying neurodegenerative disorders. In the last years, the study of possible age-related modifications in brain sensorimotor functional characteristics has been the focus of several research projects. Here we have used the transcranial magnetic stimulation (TMS)-electroencephalography (EEG) navigated co-registration to investigate the influence of physiological aging on the excitability and connectivity of the human sensorimotor cortical system. To this end, we compared the TMS-evoked EEG potentials (TEPs) collected after stimulating the dominant primary motor cortex (M1) in healthy young subjects (mean age 24.5years) with those collected in healthy older adults (mean age 67.6years). We have shown that, after stimulation of the left motor cortex, TEPs are significantly affected by physiological aging. This phenomenon has a clear spatio-temporal specificity and we speculate that normal aging per se leads to some changes in the excitability of specific cortical neural assemblies whereas other alterations could reflect compensatory mechanisms to such changes.
    背景与目标: :感觉运动皮质系统在其整个生命周期中都会发生结构和功能的变化。这些变化中的一些是生理上的并且与正常衰老过程平行,而其他一些则可能代表了神经退行性疾病的病理生理机制。近年来,对大脑感觉运动功能特征可能与年龄有关的修饰的研究一直是数个研究项目的重点。在这里,我们已经使用了经颅磁刺激(TMS)-脑电图(EEG)导航的共同注册,以研究生理老化对人类感觉运动皮层系统的兴奋性和连通性的影响。为此,我们比较了健康年轻受试者(平均年龄24.5岁)和健康老年人(平均年龄67.6岁)在刺激主要运动皮层(M1)后收集的TMS诱发的脑电势(TEP)。我们已经表明,刺激左运动皮层后,TEP受生理老化的影响很大。这种现象具有明确的时空特异性,我们推测正常衰老本身会导致特定皮层神经组件兴奋性发生某些变化,而其他变化可能反映出这种变化的补偿机制。
  • 【声门上癌的经皮激光外科手术与抢救性激光显微外科手术的功能和肿瘤学结局。】 复制标题 收藏 收藏
    DOI:10.1177/000348941212101007 复制DOI
    作者列表:Hutcheson KA,Jantharapattana K,Barringer DA,Lewin JS,Holsinger FC
    BACKGROUND & AIMS: OBJECTIVES:We evaluated the functional and oncological outcomes of transoral laser microsurgery (TLM) in patients with previously untreated supraglottic carcinoma compared with the outcomes in salvage cases after radiation-based treatment. METHODS:We conducted a retrospective case-control study at a single academic tertiary care institution. The functional outcomes were stratified by prior irradiation and were assessed at baseline, less than 1 week after operation, and at last follow-up. RESULTS:Five patients underwent TLM for previously untreated disease, and 5 previously irradiated patients underwent salvage TLM for local failure. No patient required tracheostomy. There was no local recurrence after TLM as primary therapy, and none of those patients required radiotherapy. One salvage patient developed local recurrence. The duration of feeding tube dependence (p = 0.049) and the rates of chronic aspiration (more than 1 month after operation; p = 0.048) were significantly higher in the salvage TLM cases than in the previously untreated cases. The median scores on the PSS-HN Understandability of Speech were 75 ("usually understandable") in the salvage group and 100 ("always understandable") in the previously untreated group. CONCLUSIONS:Both local control and function were better in the previously untreated patients than in the salvage patients. Our findings provide support for the use of TLM as a primary treatment modality for selected supraglottic carcinomas, but also suggest a potential for functional recovery in both previously untreated and salvage cases.
    背景与目标: 目的:我们评估了先前未经治疗的声门上癌患者经口激光显微外科手术(TLM)的功能和肿瘤学结果,与基于放射治疗的抢救病例的结果相比。
    方法:我们在一家单一的三级学术机构中进行了一项回顾性病例对照研究。功能结局通过事先照射进行分层,并在基线,手术后不到1周和最后一次随访时进行评估。
    结果:5例接受过TLM的患者先前未接受过治疗,而5例接受过放射线的患者则接受了TLM进行局部衰竭治疗。没有患者需要气管切开术。 TLM作为主要疗法后没有局部复发,而且这些患者均不需要放疗。一名抢救患者出现局部复发。抢救性TLM病例的进食管依赖性持续时间(p = 0.049)和慢性误吸率(术后1个月以上; p = 0.048)显着高于先前未治疗的病例。挽救组的PSS-HN语音可理解性中位数为75(“通常可理解”),以前未治疗的组为100(“始终可理解”)。
    结论:先前未治疗的患者的局部控制和功能均优于抢救患者。我们的发现为TLM作为选定的声门上癌的主要治疗手段提供了支持,但也暗示了先前未治疗和挽救病例的功能恢复潜力。
  • 【功能性胃灼热:临床特征和预后。】 复制标题 收藏 收藏
    DOI:10.1097/MEG.0b013e32835b108f 复制DOI
    作者列表:Surdea Blaga T,Dumitrascu D,Galmiche JP,Bruley des Varannes S
    BACKGROUND & AIMS: OBJECTIVES:Patients with heartburn and normal upper gastrointestinal endoscopy, normal oesophageal acid exposure, no symptom-reflux association and who fail to respond to a proton-pump inhibitor are classified as having functional heartburn (FH). This study aimed (i) to characterize the symptoms and functional abnormalities of patients with FH and (ii) to describe their clinical outcome. MATERIALS AND METHODS:Among all patients referred for 24 h multichannel intraluminal impedance-pH (MII-pH), patients with FH were identified. The clinical characteristics and high-resolution oesophageal pressure topography recordings of FH patients were analyzed at the time of the 24-h MII-pH test. A symptom-related and health-related quality-of-life questionnaire was then sent to FH patients to assess the long-term outcome. RESULTS:Forty patients fulfilled the criteria for FH, representing 8.5% of the referred population. Twenty-two months after initial testing, 66% of patients still suffered from heartburn. The rate of mixed reflux (liquid/gas) was higher in patients with persisting heartburn at the final evaluation (63 vs. 50%, P=0.04). Sixty-six per cent of patients had one or more manometric abnormalities. Acid clearance time in MII-pH was significantly higher in patients with weak peristalsis than patients with normal peristalsis (60 ± 45 vs. 31 ± 19 s, P=0.03). A high rate of mixed reflux and/or a manometric abnormality were associated with a higher risk of persistent heartburn. CONCLUSION:FH is a chronic disorder with persisting symptoms in two-thirds of patients. An increased rate of mixed reflux and/or the presence of manometric abnormalities are associated with a higher risk of persisting symptoms and may help to identify the population with unmet therapeutic needs.
    背景与目标: 目的:患有胃灼热和正常上消化道内窥镜检查,正常食道酸暴露,无症状-反流关联且对质子泵抑制剂无反应的患者被归类为功能性胃灼热(FH)。这项研究旨在(i)表征FH患者的症状和功能异常,以及(ii)描述其临床结局。
    材料与方法:在所有接受24 h多通道管腔内阻抗pH(MII-pH)治疗的患者中,均鉴定出FH患者。在24小时MII-pH测试时分析了FH患者的临床特征和高分辨率的食管压力地形图记录。然后将症状相关和健康相关的生活质量调查表发送给FH患者,以评估其长期预后。
    结果:40例患者符合FH标准,占推荐人群的8.5%。初始测试后的22个月,仍有66%的患者患有胃灼热。在最终评估中,持续性烧心患者的混合反流(液体/气体)比率更高(63%vs. 50%,P = 0.04)。 66%的患者有一个或多个压力异常。蠕动较弱的患者在MII-pH中的酸清除时间明显长于正常蠕动的患者(60±45 vs. 31±19 s,P = 0.03)。混合反流率高和/或测压异常与持续性烧心的风险较高相关。
    结论:FH是一种慢性疾病,在三分之二的患者中持续存在症状。混合反流率的增加和/或压力异常的存在与持续存在症状的风险较高有关,可能有助于确定治疗需求未得到满足的人群。
  • 【用于第二代生物燃料生产的超基因组功能纤维素酶的生物勘探:综述。】 复制标题 收藏 收藏
    DOI:10.1080/1040841X.2017.1337713 复制DOI
    作者列表:Tiwari R,Nain L,Labrou NE,Shukla P
    BACKGROUND & AIMS: :Second generation biofuel production has been appeared as a sustainable and alternative energy option. The ultimate aim is the development of an industrially feasible and economic conversion process of lignocellulosic biomass into biofuel molecules. Since, cellulose is the most abundant biopolymer and also represented as the photosynthetically fixed form of carbon, the efficient hydrolysis of cellulose is the most important step towards the development of a sustainable biofuel production process. The enzymatic hydrolysis of cellulose by suites of hydrolytic enzymes underlines the importance of cellulase enzyme system in whole hydrolysis process. However, the selection of the suitable cellulolytic enzymes with enhanced activities remains a challenge for the biorefinery industry to obtain efficient enzymatic hydrolysis of biomass. The present review focuses on deciphering the novel and effective cellulases from different environmental niches by unculturable metagenomic approaches. Furthermore, a comprehensive functional aspect of cellulases is also presented and evaluated by assessing the structural and catalytic properties as well as sequence identities and expression patterns. This review summarizes the recent development in metagenomics based approaches for identifying and exploring novel cellulases which open new avenues for their successful application in biorefineries.
    背景与目标: :第二代生物燃料生产已被视为一种可持续的替代能源选择。最终目的是开发一种工业上可行且经济的木质纤维素生物质转化为生物燃料分子的方法。由于纤维素是最丰富的生物聚合物,并且也表现为碳的光合作用固定形式,因此纤维素的有效水解是朝着可持续生物燃料生产工艺发展的最重要步骤。一系列水解酶对纤维素的酶促水解强调了纤维素酶系统在整个水解过程中的重要性。然而,选择具有增强活性的合适的纤维素分解酶对于生物精炼工业获得有效的生物质的酶水解仍然是一个挑战。目前的审查侧重于通过不可培养的宏基因组学方法从不同的环境利基破译新颖和有效的纤维素酶。此外,还介绍了纤维素酶的综合功能方面,并通过评估结构和催化特性以及序列同一性和表达模式来对其进行评估。这篇综述总结了基于宏基因组学的方法的最新发展,该方法用于鉴定和探索新型纤维素酶,为它们在生物精炼厂的成功应用开辟了新途径。
  • 【癫痫病的护理协调:使用社交网络分析测量神经科医生的联系。】 复制标题 收藏 收藏
    DOI:10.1016/j.yebeh.2017.05.026 复制DOI
    作者列表:Altalib HH,Fenton BT,Cheung KH,Pugh MJV,Bates J,Valente TW,Kerns RD,Brandt CA
    BACKGROUND & AIMS: OBJECTIVE:The study sought to quantify coordination of epilepsy care, over time, between neurologists and other health care providers using social network analysis (SNA). METHODS:The Veterans Health Administration (VA) instituted an Epilepsy Center of Excellence (ECOE) model in 2008 to enhance care coordination between neurologists and other health care providers. Provider networks in the 16 VA ECOE facilities (hub sites) were compared to a subset of 33 VA facilities formally affiliated (consortium sites) and 14 unaffiliated VA facilities. The number of connections between neurologists and each provider (node degree) was measured by shared epilepsy patients and tallied to generate estimates at the facility level separately within and across facilities. Mixed models were used to compare change of facility-level node degree over time across the three facility types, adjusted for number of providers per facility. RESULTS:Over the time period 2000-2013, epilepsy care coordination both within and across facilities significantly increased. These increases were seen in all three types of facilities namely hub, consortium, and unaffiliated site, relatively equally. The increase in connectivity was more dramatic with providers across facilities compared to providers within the same facilities. CONCLUSION:Establishment of the ECOE hub and spoke model contributed to an increase in epilepsy care coordination both within and across facilities from 2000 to 2013, but there was substantial variation across different facilities. SNA is a tool that may help measure coordination of specialty care.
    背景与目标: 目的:本研究试图通过社交网络分析(SNA)量化神经科医师与其他医疗保健提供者之间随着时间的推移癫痫治疗的协调性。
    方法:退伍军人卫生管理局(VA)在2008年建立了癫痫病卓越中心(ECOE)模型,以加强神经科医生与其他卫生保健提供者之间的护理协调。将16个VA ECOE设施(集线器站点)中的提供商网络与33个正式关联的VA设施(财团站点)和14个未关联的VA设施的子集进行了比较。由共享的癫痫患者测量神经科医师与每个提供者之间的联系数(节点度),并计算以在设施级别内部和设施之间分别在设施级别生成估计值。混合模型用于比较三种设施类型上设施级别节点度随时间的变化,并针对每个设施的提供者数量进行了调整。
    结果:在2000年至2013年期间,设施内和设施间的癫痫护理协调性显着提高。这些增加在三种类型的设施中都可以看到,即枢纽,财团和非附属场所,相对均等。与同一设施内的提供商相比,跨设施的提供商的连接性增长更为显着。
    结论:从2000年到2013年,建立ECOE枢纽和轮辐模型有助于增加设施内和设施之间的癫痫护理协调,但不同设施之间存在很大差异。 SNA是一种工具,可以帮助评估专科护理的协调性。
  • 【蛋白质结构域及其在真核生物中的组合的进化历史和功能意义。】 复制标题 收藏 收藏
    DOI:10.1186/gb-2007-8-6-r121 复制DOI
    作者列表:Itoh M,Nacher JC,Kuma K,Goto S,Kanehisa M
    BACKGROUND & AIMS: BACKGROUND:In higher multicellular eukaryotes, complex protein domain combinations contribute to various cellular functions such as regulation of intercellular or intracellular signaling and interactions. To elucidate the characteristics and evolutionary mechanisms that underlie such domain combinations, it is essential to examine the different types of domains and their combinations among different groups of eukaryotes. RESULTS:We observed a large number of group-specific domain combinations in animals, especially in vertebrates. Examples include animal-specific combinations in tyrosine phosphorylation systems and vertebrate-specific combinations in complement and coagulation cascades. These systems apparently underwent extensive evolution in the ancestors of these groups. In extant animals, especially in vertebrates, animal-specific domains have greater connectivity than do other domains on average, and contribute to the varying number of combinations in each animal subgroup. In other groups, the connectivities of older domains were greater on average. To observe the global behavior of domain combinations during evolution, we traced the changes in domain combinations among animals and fungi in a network analysis. Our results indicate that there is a correlation between the differences in domain combinations among different phylogenetic groups and different global behaviors. CONCLUSION:Rapid emergence of animal-specific domains was observed in animals, contributing to specific domain combinations and functional diversification, but no such trends were observed in other clades of eukaryotes. We therefore suggest that the strategy for achieving complex multicellular systems in animals differs from that of other eukaryotes.
    背景与目标: 背景:在高级多细胞真核生物中,复杂的蛋白质结构域组合有助于多种细胞功能,例如调节细胞间或细胞内信号传导和相互作用。为了阐明构成这些结构域组合基础的特征和进化机制,必须研究不同类型的结构域及其在不同组真核生物之间的组合。
    结果:我们在动物中,尤其是在脊椎动物中观察到大量特定于组的域组合。实例包括酪氨酸磷酸化系统中的动物特异性组合以及补体和凝血级联反应中的脊椎动物特异性组合。这些系统显然在这些群体的祖先中经历了广泛的发展。在现存的动物中,尤其是在脊椎动物中,动物特定的域平均比其他域具有更大的连通性,并且会导致每个动物亚组中组合数量的变化。在其他组中,较旧域的连通性平均更高。为了观察进化过程中域组合的整体行为,我们在网络分析中追踪了动物和真菌之间域组合的变化。我们的结果表明,不同的系统发生群体之间的域组合差异与不同的整体行为之间存在相关性。
    结论:在动物中观察到动物特异性结构域的快速出现,这有助于特定结构域的组合和功能的多样化,但在其他真核生物进化枝中未观察到这种趋势。因此,我们建议在动物中实现复杂的多细胞系统的策略与其他真核生物的策略不同。
  • 【单链RNA的不同功能类别之间核苷酸碱基组成的全局相似性暗示适应性进化收敛。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1997-07-01
    来源期刊:RNA
    DOI: 复制DOI
    作者列表:Schultes E,Hraber PT,LaBean TH
    BACKGROUND & AIMS: The number of distinct functional classes of single-stranded RNAs (ssRNAs) and the number of sequences representing them are substantial and continue to increase. Organizing this data in an evolutionary context is essential, yet traditional comparative sequence analyses require that homologous sites can be identified. This prevents comparative analysis between sequences of different functional classes that share no site-to-site sequence similarity. Analysis within a single evolutionary lineage also limits evolutionary inference because shared ancestry confounds properties of molecular structure and function that are historically contingent with those that are imposed for biophysical reasons. Here, we apply a method of comparative analysis to ssRNAs that is not restricted to homologous sequences, and therefore enables comparison between distantly related or unrelated sequences, minimizing the effects of shared ancestry. This method is based on statistical similarities in nucleotide base composition among different functional classes of ssRNAs. In order to denote base composition unambiguously, we have calculated the fraction G+A and G+U content, in addition to the more commonly used fraction G+C content. These three parameters define RNA composition space, which we have visualized using interactive graphics software. We have examined the distribution of nucleotide composition from 15 distinct functional classes of ssRNAs from organisms spanning the universal phylogenetic tree and artificial ribozymes evolved in vitro. Surprisingly, these distributions are biased consistently in G+A and G+U content, both within and between functional classes, regardless of the more variable G+C content. Additionally, an analysis of the base composition of secondary structural elements indicates that paired and unpaired nucleotides, known to have different evolutionary rates, also have significantly different compositional biases. These universal compositional biases observed among ssRNAs sharing little or no sequence similarity suggest, contrary to current understanding, that base composition biases constitute a convergent adaptation among a wide variety of molecular functions.

    背景与目标: 单链RNA(ssRNA)的不同功能类别的数量以及代表它们的序列数量非常可观,并且还在不断增加。在进化的背景下组织这些数据是必不可少的,但是传统的比较序列分析要求可以鉴定出同源位点。这样可防止在不共享位点间序列相似性的不同功能类别的序列之间进行比较分析。单一进化谱系中的分析也限制了进化推论,因为共享祖先混淆了分子结构和功能的特性,而这些特性在历史上与由于生物物理原因而施加的特性是相依的。在这里,我们将比较分析方法应用于不限于同源序列的ssRNA,因此可以在远距离相关或不相关的序列之间进行比较,从而最大程度地减少了共同祖先的影响。该方法基于不同功能类别的ssRNA之间核苷酸碱基组成的统计相似性。为了明确表示基础组成,除了更常用的分数G C含量外,我们还计算了分数G A和G U含量。这三个参数定义了RNA组成空间,我们已经使用交互式图形软件对其进行了可视化。我们已经检查了来自15种不同功能类别的ssRNAs的核苷酸组成的分布,这些ssRNAs来自横跨普遍的系统树和体外进化的人工核酶的生物。出乎意料的是,这些功能分布在功能类内和功能类之间的G A和G U含量上始终存在偏差,而与G C含量的可变性无关。另外,对二级结构元件的基本组成的分析表明,已知具有不同进化速率的成对和未成对核苷酸也具有明显不同的组成偏差。与目前的理解相反,这些在几乎没有序列相似性或几乎没有序列相似性的ssRNA中观察到的这些普遍组成偏倚表明,碱基组成偏倚构成了多种分子功能之间的收敛适应。

  • 【衣原体和大肠杆菌中sigma28调控基因的计算机预测和功能验证。】 复制标题 收藏 收藏
    DOI:10.1128/JB.01082-06 复制DOI
    作者列表:Yu HH,Kibler D,Tan M
    BACKGROUND & AIMS: :sigma(28) RNA polymerase is an alternative RNA polymerase that has been proposed to have a role in late developmental gene regulation in Chlamydia, but only a single target gene has been identified. To discover additional sigma(28)-dependent genes in the Chlamydia trachomatis genome, we applied bioinformatic methods using a probability weight matrix based on known sigma(28) promoters in other bacteria and a second matrix based on a functional analysis of the sigma(28) promoter. We tested 16 candidate sigma(28) promoters predicted with these algorithms and found that 5 were active in a chlamydial sigma(28) in vitro transcription assay. hctB, the known sigma(28)-regulated gene, is only expressed late in the chlamydial developmental cycle only, and two of the newly identified sigma(28) target genes (tsp and tlyC_1) also have late expression profiles, providing support for sigma(28) as a regulator of late gene expression. One of the other novel sigma(28)-regulated genes is dnaK, a known heat shock-responsive gene, suggesting that sigma(28) RNA polymerase may be involved in the response to cellular stress. Our sigma(28) prediction algorithm can be applied to other bacteria, and by performing a similar analysis on the Escherichia coli genome, we have predicted and functionally identified five previously unknown sigma(28)-regulated genes in E. coli.
    背景与目标: :sigma(28)RNA聚合酶是一种替代性RNA聚合酶,已提出在衣原体的晚期发育基因调控中起作用,但仅鉴定了一个靶基因。为了在沙眼衣原体基因组中发现其他依赖sigma(28)的基因,我们应用了生物信息学方法,该方法使用了基于其他细菌中已知sigma(28)启动子的概率权重矩阵和基于sigma(28)功能分析的第二矩阵的概率信息权重矩阵。 )启动子。我们测试了用这些算法预测的16个候选sigma(28)启动子,发现5个在衣原体sigma(28)体外转录测定中具有活性。 hctB是已知的sigma(28)调控基因,仅在衣原体发育周期的后期表达,而且新鉴定的sigma(28)目标基因中的两个(tsp和tlyC_1)也具有较晚的表达谱,为sigma提供了支持(28)作为晚期基因表达的调节剂。另一个新的sigma(28)调控基因是dnaK,一种已知的热激反应基因,表明sigma(28)RNA聚合酶可能参与了对细胞应激的反应。我们的sigma(28)预测算法可以应用于其他细菌,并且通过对大肠杆菌基因组进行类似分析,我们已经预测并在功能上鉴定了大肠杆菌中五个以前未知的sigma(28)调控基因。
  • 【哮喘患者通过不同装置吸入沙丁胺醇对支气管扩张剂反应的起效速度:一种基于功能拮抗作用的生物测定法。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2125.2006.02641.x 复制DOI
    作者列表:Lavorini F,Geri P,Mariani L,Marmai C,Maluccio NM,Pistolesi M,Fontana GA
    BACKGROUND & AIMS: AIMS:To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. METHODS:Eighteen patients inhaled methacholine (MCh) until FEV(1) decreased by 35% of control. Following administration of placebo, 200 microg salbutamol or 400 microg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV(1) and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. RESULTS:For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV(1) and volume-adjusted mid-expiratory flow similar to those obtained with 200 microg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) microg, 395 (95% CI 388, 404) microg and 404 (95% CI 393, 415) microg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). CONCLUSIONS:Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus.
    背景与目标: 目的:评估沙丁胺醇通过带间隔垫片的定量吸入器(pMDI Volumatic)和干粉吸入器(Diskus)给药后支气管扩张的发生速度,以及这些装置在哮喘患者中使用乙酰甲胆碱的相对效力引起的支气管收缩。
    方法:十八例患者吸入乙酰甲胆碱(MCh),直到FEV(1)降低至对照组的35%。通过pMDI Volumatic或Diskus给予安慰剂,200μg沙丁胺醇或400μg沙丁胺醇后,我们计算了药物给药所花费的时间以及MCh后强制肺活量(FVC),FEV(90)出现90%的增加)和经过体积调整的呼气中气流量(恢复时间)。通过使用2乘2 Finney平行回归方法计算两个吸入装置要达到相似的恢复时间所要输送的沙丁胺醇剂量,以及该装置的相对效能。
    结果:对于所有功能变量,pMDI Volumatic的恢复时间比Diskus试验明显缩短(P <0.01)。与通过pMDI Volumatic施用200微克沙丁胺醇获得的FVC,FEV(1)和经体积调节的呼气中流的恢复时间相比,由Diskus输送的沙丁胺醇的剂量为558(95%CI 537,579) )微克,395(95%CI 388、404)微克和404(95%CI 393、415)微克,分别对应于2.79(95%CI 2.68、2.90),1.98(95%CI 1.94, 2.02)和2.02(95%CI 1.96,2.07)。
    结论:通过pMDI Volumatic给予沙丁胺醇比通过Diskus可以更快地逆转诱导的支气管收缩。使用pMDI Volumatic靶向肺的沙丁胺醇剂量约为使用Diskus的两倍。
  • 【在高活性抗逆转录病毒疗法期间,通过疫苗接种驱动的功能性HIV-1特异性CD8 T细胞扩增中广泛使用TCR。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.179.1.597 复制DOI
    作者列表:Yang H,Dong T,Turnbull E,Ranasinghe S,Ondondo B,Goonetilleke N,Winstone N,di Gleria K,Bowness P,Conlon C,Borrow P,Hanke T,McMichael A,Dorrell L
    BACKGROUND & AIMS: :During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses; however, the potential to modulate the repertoire of functional virus-specific T cells by immunotherapy has not been explored. To investigate this, we analyzed the TCR Vbeta usage of CD8+ T cells populations which were expanded following vaccination with modified vaccinia virus Ankara expressing a HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected patients receiving highly active antiretroviral therapy. Vaccinations induced the re-expansion of HIV-1-specific CD8+ T cells and these showed broad TCR Vbeta usage which was maintained for at least 1 year in some individuals. By contrast, virus-specific CD8+ T cell populations in the same donors which failed to expand after vaccination and in unvaccinated controls were oligoclonal. Simultaneously, we observed that CD8+ T cells recognizing vaccine-derived HIV-1 epitopes displayed enhanced capacity to proliferate and to inhibit HIV-1 replication in vitro, following MVA.HIVA immunizations. Taken together, these data indicate that an attenuated viral-vectored vaccine can modulate adaptive CD8+ T cell responses to HIV-1 and improve their antiviral functional capacity. The potential therapeutic benefit of this vaccination approach warrants further investigation.
    背景与目标: :在慢性HIV-1感染期间,持续的病毒复制与病毒特异性CD8 T细胞的增殖能力受损以及寡克隆T细胞群体的扩张和持续存在有关。 TCR的使用可能会显着影响CD8 T细胞介导的对AIDS病毒的控制;然而,尚未探索通过免疫疗法调节功能性病毒特异性T细胞库的潜力。为了对此进行调查,我们分析了在接受高活性抗逆转录病毒治疗的HIV-1感染患者中,用表达HIV-1 gag /多表位免疫原(MVA.HIVA)的改良牛痘病毒安卡拉疫苗接种后扩大的CD8 T细胞群体的TCR Vbeta使用治疗。疫苗接种可诱导HIV-1特异性CD8 T细胞的再扩增,这些疫苗显示出广泛的TCR Vbeta使用率,在某些人中至少维持了1年。相比之下,相同供体中的病毒特异性CD8 T细胞群体在接种疫苗后未能扩增,而在未接种疫苗的对照组中则是寡克隆的。同时,我们观察到,在MVA.HIVA免疫后,识别疫苗衍生的HIV-1表位的CD8 T细胞在体外具有增强的增殖能力和抑制HIV-1复制的能力。综上所述,这些数据表明减毒的病毒载体疫苗可以调节对HIV-1的适应性CD8 T细胞应答并提高其抗病毒功能能力。这种疫苗接种方法的潜在治疗益处值得进一步研究。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录