• 【NLRX1通过控制线粒体活性来抑制组织损伤中的氧化应激和细胞凋亡。】 复制标题 收藏 收藏
    DOI:10.1084/jem.20161031 复制DOI
    作者列表:Stokman G,Kors L,Bakker PJ,Rampanelli E,Claessen N,Teske GJD,Butter L,van Andel H,van den Bergh Weerman MA,Larsen PWB,Dessing MC,Zuurbier CJ,Girardin SE,Florquin S,Leemans JC
    BACKGROUND & AIMS: :Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 is a receptor of the innate immune system that is ubiquitously expressed and localized in mitochondria. We investigated whether NLRX1 may act at the interface of metabolism and innate immunity in a model of oxidative stress. Using a chimeric mouse model for renal ischemia-reperfusion injury, we found that NLRX1 protects against mortality, mitochondrial damage, and epithelial cell apoptosis in an oxidative stress-dependent fashion. We found that NLRX1 regulates oxidative phosphorylation and cell integrity, whereas loss of NLRX1 results in increased oxygen consumption, oxidative stress, and subsequently apoptosis in epithelial cells during ischemia-reperfusion injury. In line, we found that NLRX1 expression in human kidneys decreased during acute renal ischemic injury and acute cellular rejection. Although first implicated in immune regulation, we propose that NLRX1 function extends to the control of mitochondrial activity and prevention of oxidative stress and apoptosis in tissue injury.
    背景与目标: 线粒体功能障碍是急性和慢性肾脏疾病中最主要的氧化应激源。 NLRX1是先天免疫系统的受体,在线粒体中普遍表达和定位。我们调查了NLRX1是否可能在氧化应激模型中的新陈代谢和先天免疫的界面上起作用。使用针对肾缺血-再灌注损伤的嵌合小鼠模型,我们发现NLRX1以氧化应激依赖性的方式防止死亡,线粒体损伤和上皮细胞凋亡。我们发现NLRX1调节氧化磷酸化和细胞完整性,而NLRX1的缺失导致缺血再灌注损伤期间上皮细胞的耗氧量增加,氧化应激和随后的细胞凋亡。一致地,我们发现在急性肾缺血性损伤和急性细胞排斥期间,人肾脏中的NLRX1表达降低。尽管首先涉及免疫调节,但我们认为NLRX1功能扩展到线粒体活性的控制以及组织损伤中氧化应激和细胞凋亡的预防。
  • 【青少年内在化和外在化症状的测试,可以作为创伤暴露和创伤后应激障碍类型的前瞻性预测指标。】 复制标题 收藏 收藏
    DOI:10.1002/jts.21751 复制DOI
    作者列表:Haller M,Chassin L
    BACKGROUND & AIMS: :The present study utilized longitudinal data from a high-risk community sample (N = 377; 166 trauma-exposed; 202 males; 175 females; 73% non-Hispanic Caucasian) to test pretrauma measures of adolescent internalizing and externalizing symptoms as unique prospective predictors of type of trauma exposure and PTSD over and above the influence of correlated family adversity (a composite of family conflict, stress, and parental psychopathology). Data were analyzed with logistic and multinomial logistic regressions. Results indicated that females, but not males, with higher levels of internalizing (OR = 2.91) and externalizing (OR = 2.37) symptoms during adolescence were significantly more likely to be exposed to assaultive violence (over and above family adversity). In fact, males with higher levels of internalizing symptoms were significantly less likely to be exposed to assaultive violence (OR = 0.54). Neither internalizing nor externalizing symptoms uniquely predicted exposure to traumatic events that did not involve assaultive violence. Among trauma-exposed participants, the unique association between internalizing symptoms and later PTSD yielded an odds ratio of 1.79 (p = .07) over and above the influences of family adversity, type of trauma exposure, and gender. Assaultive violence exposure fully mediated the association between females' externalizing symptoms and future PTSD. Findings may help inform the prevention of both assaultive violence exposure and PTSD.
    背景与目标: :本研究利用来自高风险社区样本(N = 377;暴露于166的外伤​​; 202男性; 175女性; 73%的非西班牙裔白种人)的纵向数据来测试青少年内在和外在症状的创伤前测量方法,作为独特的前瞻性研究除了相关的家庭逆境影响(家庭冲突,压力和父母的心理病理因素的综合影响)以外,还可以预测创伤暴露和PTSD的类型。使用logistic和多项式logistic回归分析数据。结果表明,青春期出现内在化(OR = 2.91)和外在化(OR = 2.37)症状的女性(而非男性)明显更有可能遭受攻击性暴力(家庭逆境以上)。实际上,具有较高内在症状水平的男性遭受攻击性暴力的可能性大大降低(OR = 0.54)。内在或外在症状都不能唯一预测暴露于不涉及攻击性暴力的创伤事件。在遭受创伤的参与者中,内在症状与后来的创伤后应激障碍之间的独特关联产生了1.79(p = .07)的优势比,高于家庭逆境,创伤暴露类型和性别的影响。攻击性暴力暴露完全介导了女性的外在症状与未来PTSD之间的关联。研究结果可能有助于预防攻击性暴力暴露和PTSD。
  • 【实验诱发的压力后,二元应对,不安全的依恋和皮质醇压力恢复。】 复制标题 收藏 收藏
    DOI:10.1037/a0030356 复制DOI
    作者列表:Meuwly N,Bodenmann G,Germann J,Bradbury TN,Ditzen B,Heinrichs M
    BACKGROUND & AIMS: :Evidence for the stress-buffering effects of social support in intimate relationships raises important questions about whether partner support promotes recovery in physiological systems implicated in physical health. The present study examined (a) whether observed dyadic coping enhances cortisol stress recovery and (b) whether a stressed partner's self-reported attachment anxiety and avoidance moderate these effects. Stress was experimentally induced by asking either the man or woman in 123 heterosexual couples to participate in a standardized public speaking task. Stressed individuals recovered faster from stress the more positive dyadic coping they received from the partner, with women high in attachment anxiety benefiting less from these behaviors. Attachment avoidance did not moderate these associations. This study highlights the value of examining the interplay between partners' behaviors and attachment orientations in order to understand the impact of stress on close relationships and partners' health.
    背景与目标: :在亲密关系中社会支持对压力的缓冲作用的证据提出了一个重要问题,即伴侣支持是否会促进与身体健康有关的生理系统的恢复。本研究调查了(a)观察到的二元应对是否增强了皮质醇应激恢复,以及(b)应激伴侣的自我报告的焦虑和避免焦虑是否减轻了这些影响。通过让123对异性恋夫妇中的男人或女人参加标准化的公开演讲任务,实验性地诱发了压力。压力大的人从伴侣那里得到的积极积极的应对使他们从压力中恢复得更快,而依恋焦虑高的女性则从这些行为中受益较少。避免依恋并没有减轻这些联系。这项研究强调了检查伴侣行为与依恋取向之间相互作用的价值,以了解压力对亲密关系和伴侣健康的影响。
  • 【更正:肝p63通过IKKβ/ ER应激调节脂肪变性。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms16059 复制DOI
    作者列表:
    BACKGROUND & AIMS: :This corrects the article DOI: 10.1038/ncomms15111.
    背景与目标: :这样可以更正文章DOI:10.1038 / ncomms15111。
  • 【海地地震后的精神病理学:基于人群的创伤后应激障碍和重度抑郁症研究。】 复制标题 收藏 收藏
    DOI:10.1002/da.22007 复制DOI
    作者列表:Cerdá M,Paczkowski M,Galea S,Nemethy K,Péan C,Desvarieux M
    BACKGROUND & AIMS: BACKGROUND:In the first population-based study of psychopathology conducted in Haiti, we documented earthquake-related experiences associated with risk for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) 2-4 months following the 2010 Haiti earthquake. METHODS:A population-based survey was conducted of 1,323 survivors randomly selected from the general nondisplaced community, internally displaced persons camps, and a community clinic. Respondents were from the Nazon area of Port-au-Prince, ∼20 miles from the epicenter. RESULTS:Respondents (90.5%) reported at least one relative/close friend injured/killed, 93% saw dead bodies, and 20.9% lost their job post-earthquake. The prevalence of PTSD (24.6%) and MDD (28.3%) was high. History of violent trauma was associated with risk of PTSD and MDD (adjusted odds ratio [AOR] 1.4, 95% confidence interval [CI], 1.0-1.9; AOR, 1.7, 95% CI 1.3, 2.2, respectively). Low social support (AOR, 1.7, 95% CI 1.2, 2.3; AOR 1.4, 95% CI 1.0, 1.9, respectively) increased risk of PTSD and MDD among women. Suffering damage to the home increased risk of MDD in males (AOR 2.8, 95% CI 1.5, 5.5). Associations between being trapped in rubble, major damage to house, job loss, and PTSD; and participation in rescue/recovery, friends/family injured/killed, and MDD varied based on prior history of violent trauma. CONCLUSIONS:Addressing mental health in a post-earthquake setting such as Haiti will require focusing resources on screening and treatment of identified vulnerable groups while targeting improvement of post-earthquake living conditions. Investment in sources of social support for women may make help mitigate the vulnerability of women to PTSD and MDD.
    背景与目标: 背景:在海地进行的第一项基于人群的心理病理学研究中,我们记录了与地震相关的经历,这些经历与2010年海地地震发生后2-4个月的创伤后应激障碍(PTSD)和重度抑郁症(MDD)风险有关。
    方法:基于人口的调查是对从普通非流离失所社区,国内流离失所者营地和社区诊所中随机选择的1,323名幸存者进行的。受访者来自太子港的纳松地区,距震中约20英里。
    结果:受访者(90.5%)报告说,至少有一个亲戚/密友受伤/被杀,93%的人有尸体,20.9%的人在地震后丧生。 PTSD(24.6%)和MDD(28.3%)的患病率很高。暴力创伤史与PTSD和MDD的风险有关(校正比值比[AOR] 1.4,95%置信区间[CI],1.0-1.9; AOR,1.7,95%CI 1.3,2.2)。较低的社会支持(分别为AOR,1.7、95%CI 1.2、2.3,AOR 1.4、95%CI 1.0、1.9)增加了妇女罹患PTSD和MDD的风险。房屋遭受损坏会增加男性罹患MDD的风险(AOR 2.8,95%CI 1.5,5.5)。被困在瓦砾中,对房屋的重大破坏,失业和PTSD之间的关联;根据先前的暴力创伤史,参与救援/恢复,朋友/家人受伤/被杀以及MDD的情况也有所不同。
    结论:在海地这样的地震后环境中解决心理健康问题,将需要把资源集中在筛查和治疗已确定的弱势群体上,同时着眼于改善地震后的生活条件。对妇女的社会支持来源的投资可能有助于减轻妇女对PTSD和MDD的脆弱性。
  • 【在小鼠下丘脑器官型培养物中,Sequestosome 1(SQSTM1 / p62)在内质网应激下维持蛋白质折叠能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2017.06.014 复制DOI
    作者列表:Tominaga T,Goto M,Onoue T,Mizoguchi A,Sugiyama M,Tsunekawa T,Hagiwara D,Morishita Y,Ito Y,Iwama S,Suga H,Banno R,Arima H
    BACKGROUND & AIMS: :Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study. Cultures from p62KO mice showed significantly reduced formation of LC3-GFP puncta, an index of autophagosome formation, in response to the chemical ER stressor thapsigargin compared to wild-type (WT) cultures. Hypothalamic cultures from p62KO mice exhibited higher basal expression of the UPR/ER stress markers CHOP mRNA and ATF4 mRNA than WT cultures. Thapsigargin enhanced CHOP, ATF4, and BiP mRNA as well as p-eIF2α protein expression in both WT and p62KO cultures, but all peak values were greater in p62KO cultures. A proteasome inhibitor increased p62 expression in WT cultures and upregulated the UPR/ER stress markers CHOP mRNA and ATF4 mRNA in both genotypes, but to a greater extent in p62KO cultures. Therefore, p62 deficiency disturbed autophagosome formation and enhanced both basal and chemically induced ER stress, suggesting that p62 serves to prevent ER stress in mouse hypothalamus by maintaining protein folding capacity.
    背景与目标: :Sequestosome 1(SQSTM1)也称为泛素结合蛋白p62(p62)是一种货物蛋白,通过选择性自噬作用参与错折叠蛋白的降解。自噬的中断和错误折叠的蛋白质在内质网(ER)中的积累会导致ER应激。内质网应激与几种神经退行性疾病和肥胖有关。由于据报道,敲除p62(p62KO)会诱发小鼠肥胖,因此在本研究中,我们使用小鼠器官培养物检查了p62如何导致ER应激以及下丘脑中未折叠的蛋白反应(UPR)。与野生型(WT)培养相比,来自p62KO小鼠的培养物响应化学ER应激毒胡萝卜素,显示出LC3-GFP点的形成显着减少,这是自噬体形成的指标。来自p62KO小鼠的下丘脑培养物比WT培养物具有更高的UPR / ER应激标志物CHOP mRNA和ATF4 mRNA的基础表达。 Thapsigargin在WT和p62KO培养物中均增强了CHOP,ATF4和BiP mRNA以及p-eIF2α蛋白的表达,但在p62KO培养物中所有峰值均更大。蛋白酶体抑制剂增加了WT培养物中p62的表达,并上调了两种基因型的UPR / ER应激标记CHOP mRNA和ATF4 mRNA,但在p62KO培养物中的表达更大。因此,p62缺乏会干扰自噬体的形成,并增强基础和化学诱导的ER应激,提示p62通过维持蛋白质折叠能力来预防小鼠下丘脑的ER应激。
  • 【新加坡和印度对压力的心血管反应。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpsycho.2012.11.011 复制DOI
    作者列表:Kaur D,Bishop GD
    BACKGROUND & AIMS: BACKGROUND:Epidemiological studies have shown significant ethnic differences in coronary heart disease death rates with South Asians showing significantly greater coronary heart disease mortality than other groups. PURPOSE:This research examined ethnic differences in cardiovascular reactivity (CVR) among Chinese, Malays and Indians in Singapore as well as a sample of Indians living in India. METHODS:Experiment 1 examined differences across 303 Chinese, Malay and Indian undergraduates in Singapore, while Experiment 2 looked at differences in CVR between Indian participants from Singapore, and 145 Indians living in India. Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI) and total peripheral resistance index (TPRI) were measured during baselines and five laboratory tasks. RESULTS:Ethnicity main effects for SBP and CI reactivity were obtained in Experiment 1, with Indians showing significantly lower BP and CI reactivity than the Chinese and Malays. Significant main effects for sex were found with females showing lower reactivity than males for TPRI, and greater reactivity than males for HR and CI. Experiment 2 found that participants from India showed higher reactivity for SBP, HR and CI, while Indian participants from Singapore showed higher TPRI reactivity. These differences, however, often varied by task. CONCLUSIONS:These results point to differences in CVR among ethnic groups in Singapore as well as between Indians living in India and those living in Singapore. These differences may reflect cultural differences and need to be explored further with respect to their relationship to different rates of coronary heart disease among these groups.
    背景与目标: 背景:流行病学研究表明,冠心病死亡率的种族差异显着,南亚人显示冠心病死亡率明显高于其他人群。
    目的:本研究调查了新加坡华人,马来人和印第安人以及居住在印度的印第安人样本中心血管反应性(CVR)的种族差异。
    方法:实验1考察了新加坡303名华裔,马来裔和印度裔本科生之间的差异,而实验2则考察了来自新加坡的印度裔参与者和居住在印度的145名印度裔之间的CVR差异。在基线和五个实验室任务期间测量了收缩压和舒张压(SBP,DBP),心率(HR),心脏指数(CI)和总外周阻力指数(TPRI)。
    结果:种族对SBP和CI反应性的主要影响是在实验1中获得的,印度人的BP和CI反应性明显低于华人和马来人。发现性别具有重大的主要影响,女性对TPRI的反应性低于男性,而对HR和CI的反应性则高于男性。实验2发现印度参与者对SBP,HR和CI的反应性更高,而新加坡印度参与者对TPRI的反应性更高。但是,这些差异通常因任务而异。
    结论:这些结果表明,新加坡各族裔之间以及居住在印度的印度人与居住在新加坡的印度人之间的CVR差异。这些差异可能反映了文化差异,因此需要进一步探讨这些差异与这些人群中冠心病发病率的关系。
  • 【MDMA(±3,4-亚甲二氧基甲基苯丙胺)辅助的心理疗法用于治疗顽固性慢性创伤后应激障碍(PTSD)的随机对照试验研究。】 复制标题 收藏 收藏
    DOI:10.1177/0269881112464827 复制DOI
    作者列表:Oehen P,Traber R,Widmer V,Schnyder U
    BACKGROUND & AIMS: :Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).
    背景与目标: 美国(1970年代至1985年)和瑞士(1988-1993年)的精神科医生和心理治疗师合法地将MDMA用作处方药,以提高心理疗法的有效性。早期报道表明,它可用于治疗与创伤有关的疾病。最近,第一个完成的针对PTSD的MDMA辅助心理治疗的初步研究取得了令人鼓舞的结果。旨在测试MDMA辅助心理疗法在治疗难治性PTSD患者中的安全性和有效性;我们的随机,双盲,活性安慰剂对照试验招募了12名患者,分别接受低剂量(25 mg,加上12.5 mg补充剂量)或全剂量MDMA(125 mg,加上62.5 mg补充剂量)治疗。在三个实验阶段中使用MDMA,并在每周的非药物心理治疗阶段中进行穿插。所使用的结果指标是临床医生管理的PTSD量表(CAPS)和创伤后诊断量表(PDS)。在基线时,第二和第三次MDMA疗程后三周(治疗结束)以及2个月和1年的随访中对患者进行评估。我们发现,在临床环境中可以安全地进行MDMA辅助的心理治疗。没有发生与药物有关的严重不良事件。尽管在临床和统计学上自我报告(PDS)的改善(p = 0.014),但CAPS评分没有统计学上的显着降低(p = 0.066)。在1年的随访中,CAPS评分进一步提高。此外,三个MDMA会话比两个更有效(p = 0.016)。
  • 【H3K36甲基化通过增强转录保真度来调节酿酒酵母中的营养应激反应。】 复制标题 收藏 收藏
    DOI:10.1016/j.celrep.2017.05.057 复制DOI
    作者列表:McDaniel SL,Hepperla AJ,Huang J,Dronamraju R,Adams AT,Kulkarni VG,Davis IJ,Strahl BD
    BACKGROUND & AIMS: :Set2-mediated histone methylation at H3K36 regulates diverse activities, including DNA repair, mRNA splicing, and suppression of inappropriate (cryptic) transcription. Although failure of Set2 to suppress cryptic transcription has been linked to decreased lifespan, the extent to which cryptic transcription influences other cellular functions is poorly understood. Here, we uncover a role for H3K36 methylation in the regulation of the nutrient stress response pathway. We found that the transcriptional response to nutrient stress was dysregulated in SET2-deleted (set2Δ) cells and was correlated with genome-wide bi-directional cryptic transcription that originated from within gene bodies. Antisense transcripts arising from these cryptic events extended into the promoters of the genes from which they arose and were associated with decreased sense transcription under nutrient stress conditions. These results suggest that Set2-enforced transcriptional fidelity is critical to the proper regulation of inducible and highly regulated transcription programs.
    背景与目标: :Set2介导的H3K36的组蛋白甲基化调节各种活动,包括DNA修复,mRNA剪接和抑制不适当的(隐式)转录。尽管Set2未能抑制隐式转录与降低寿命有关,但对隐式转录影响其他细胞功能的程度了解甚少。在这里,我们揭示了H3K36甲基化在营养胁迫响应途径调控中的作用。我们发现,对营养胁迫的转录反应在SET2缺失(set2Δ)细胞中失调,并且与源自基因体内的全基因组双向隐秘转录相关。由这些隐性事件引起的反义转录本延伸到它们起源的基因的启动子中,并与在营养胁迫条件下的有义转录减少有关。这些结果表明,Set2增强的转录保真度对于诱导性和高度调控的转录程序的正确调控至关重要。
  • 【神经血管单位和剂量对VEGF毒性的影响:对氧化应激和凝血酶的作用。】 复制标题 收藏 收藏
    DOI:10.3233/JAD-121636 复制DOI
    作者列表:Sanchez A,Tripathy D,Luo J,Yin X,Martinez J,Grammas P
    BACKGROUND & AIMS: :Bidirectional communication between neurons and vascular cells is important to the maintenance of the central nervous system (CNS) milieu. Vascular endothelial growth factor (VEGF), through its ability to affect both vascular and neuronal cells, is likely a key protein in this process. Despite considerable literature documenting a neuroprotective function for VEGF, overexpression of this protein has also been shown in a wide variety of CNS diseases, including Alzheimer's disease (AD). Increased oxidative stress and elevated thrombin levels have also been documented in AD, specifically in the microvasculature. The aim of the current study is to examine endothelial cells and neurons in vitro to determine the effects of oxidative stress and thrombin on VEGF release as well as the effects of low and high dose VEGF on neuronal viability. The data show that microvessels isolated from AD patients secrete significantly higher levels of VEGF compared to control-derived vessels. Exposure of brain endothelial cells to oxidative stress (sodium nitroprusside, menadione, or hydrogen peroxide) or thrombin significantly increases VEGF expression. Exposure of cultured neurons to oxidative stress increases expression of thrombin. Treating rat cortical neurons with high dose VEGF (≥500 ng/ml) decreases neuronal survival and expression of the anti-apoptotic protein Bcl-2 while increasing proapoptic proteins caspase 3 and phosphorylated p38 MAPK. High dose VEGF also negates the decrease in amyloid-β evoked by low dose VEGF. These results suggest that despite literature supporting neuroprotective effects of this protein, caution is warranted prior to implementation of VEGF as a therapeutic in the brain.
    背景与目标: :神经元与血管细胞之间的双向通讯对于维持中枢神经系统(CNS)环境至关重要。血管内皮生长因子(VEGF)通过影响血管和神经元细胞的能力,很可能是该过程中的关键蛋白。尽管有大量文献记载了VEGF的神经保护功能,但该蛋白的过表达也已在多种中枢神经系统疾病(包括阿尔茨海默氏病(AD))中显示。在AD中,特别是在微脉管系统中,也已经证明了氧化应激的增加和凝血酶水平的升高。本研究的目的是在体外检查内皮细胞和神经元,以确定氧化应激和凝血酶对VEGF释放的影响以及低剂量和高剂量VEGF对神经元生存力的影响。数据显示,与对照来源的血管相比,从AD患者中分离出的微血管分泌的VEGF水平明显更高。将脑内皮细胞暴露于氧化应激(硝普钠,甲萘醌或过氧化氢钠)或凝血酶会显着增加VEGF的表达。培养的神经元暴露于氧化应激会增加凝血酶的表达。用高剂量VEGF(≥500ng / ml)治疗大鼠皮质神经元可降低神经元存活率和抗凋亡蛋白Bcl-2的表达,同时增加促凋亡蛋白caspase 3和磷酸化的p38 MAPK。高剂量VEGF还可以抵消低剂量VEGF引起的淀粉样β的减少。这些结果表明,尽管有文献支持该蛋白的神经保护作用,但在将VEGF用作脑部治疗剂之前,仍应谨慎行事。
  • 【在生命早期处于应激状态的大鼠的神经发育里程碑异常。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2007.04.007 复制DOI
    作者列表:Mesquita AR,Pêgo JM,Summavielle T,Maciel P,Almeida OF,Sousa N
    BACKGROUND & AIMS: :Manipulation of the corticosteroid milieu by interfering with the mother-newborn relationship has received much attention because of its potential bearing on psychopathology later in life. In the present study, infant rats that were deprived of maternal contact between the 2nd and the 15th postnatal days (MS2-15) for 6 h/day were subjected to a systematic assessment of neurodevelopmental milestones between postnatal days 2 and 21. The analyses included measurements of physical growth and maturation and evaluation of neurological reflexes. Although some somatic milestones (e.g. eye opening) were anticipated, MS2-15 animals showed retardation in the acquisition of postural reflex, air righting and surface righting reflexes, and in the wire suspension test; the latter two abnormalities were only found in males. A gender effect was also observed in negative geotaxis, with retardation being observed in females but not males. To better understand the delay of neurological maturation in MS2-15 rats, we determined the levels of various monoamines in different regions of the brain stem, including the vestibular area, the substantia nigra, ventral tegmental area and dorsal raphe nuclei. In the vestibular region of MS2-15 rats the levels of 5-HT were reduced, while 5-HT turnover was increased. There was also a significant increase of the 5-HT turnover in MS2-15 animals in the raphe nuclei, mainly due to increased 5-hydroxyindoleacetic acid (5-HIAA) levels, and an increase of 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the ventral tegmental area (VTA) of stressed females. No significant differences were found in the immunohistochemical sections for tyrosine and tryptophan hydroxylase in these regions of the brain stem. In conclusion, the present results show that postnatal stress induces signs of neurological pathology that may contribute to the genesis of behavioral abnormalities later in life.
    背景与目标: :通过干扰母亲与新生儿的关系来操纵皮质类固醇环境受到了广泛的关注,因为它有可能影响以后的心理病理学。在本研究中,对在出生后第2天和第15天(MS2-15)之间失去母体接触6小时/天的幼鼠进行了系统评估,评估了出生后第2天和第21天之间的神经发育里程碑。身体生长和成熟的测量以及神经反射的评估。尽管可以预见会有一些身体上的里程碑(例如睁眼),但MS2-15动物在姿势反射,空气正直和表面正直反射的获得以及钢丝悬吊测试中表现出迟缓性;后两个异常仅在男性中发现。在负地轴方向上也观察到性别效应,在雌性中观察到发育迟缓,而雄性中观察不到。为了更好地了解MS2-15大鼠神经系统成熟的延迟,我们确定了脑干不同区域(包括前庭区,黑质,腹侧被盖区和背ra核)中各种单胺的水平。在MS2-15大鼠的前庭区域,5-HT水平降低,而5-HT周转增加。缝核中MS2-15动物中5-HT的转换也显着增加,这主要是由于5-羟基吲哚乙酸(5-HIAA)水平的增加和3,4-二羟基苯基乙酸(DOPAC)的增加压力女性腹侧被盖区(VTA)的水平。在脑干的这些区域中,酪氨酸和色氨酸羟化酶的免疫组织化学切片未发现明显差异。总之,本研究结果表明,产后应激会诱发神经病理学征象,这可能有助于以后生活中行为异常的发生。
  • 【由过量表达的异源α-淀粉酶引起的生产和分泌应激导致枯草芽孢杆菌中的孢子形成受到抑制,并且活动期延长。】 复制标题 收藏 收藏
    DOI:10.1128/AEM.00472-07 复制DOI
    作者列表:Lulko AT,Veening JW,Buist G,Smits WK,Blom EJ,Beekman AC,Bron S,Kuipers OP
    BACKGROUND & AIMS: :Transcriptome analysis was used to investigate the global stress response of the gram-positive bacterium Bacillus subtilis caused by overproduction of the well-secreted AmyQ alpha-amylase from Bacillus amyloliquefaciens. Analyses of the control and overproducing strains were carried out at the end of exponential growth and in stationary phase, when protein secretion from B. subtilis is optimal. Among the genes that showed increased expression were htrA and htrB, which are part of the CssRS regulon, which responds to high-level protein secretion and heat stress. The analysis of the transcriptome profiles of a cssS mutant compared to the wild type, under identical secretion stress conditions, revealed several genes with altered transcription in a CssRS-dependent manner, for example, citM, ylxF, yloA, ykoJ, and several genes of the flgB operon. However, high-affinity CssR binding was observed only for htrA, htrB, and, possibly, citM. In addition, the DNA macroarray approach revealed that several genes of the sporulation pathway are downregulated by AmyQ overexpression and that a group of motility-specific (sigmaD-dependent) transcripts were clearly upregulated. Subsequent flow-cytometric analyses demonstrate that, upon overproduction of AmyQ as well as of a nonsecretable variant of the alpha-amylase, the process of sporulation is severely inhibited. Similar experiments were performed to investigate the expression levels of the hag promoter, a well-established reporter for sigmaD-dependent gene expression. This approach confirmed the observations based on our DNA macroarray analyses and led us to conclude that expression levels of several genes involved in motility are maintained at high levels under all conditions of alpha-amylase overproduction.
    背景与目标: :转录组分析用于研究革兰氏阳性枯草芽孢杆菌的总体应激反应,该酶是由解淀粉芽孢杆菌分泌的大量分泌良好的AmyQα-淀粉酶引起的。当枯草芽孢杆菌的蛋白质分泌最适时,在指数生长结束时和在稳定期进行对照和高产菌株的分析。显示出增加表达的基因中有htrA和htrB,它们是CssRS regulon的一部分,对高水平的蛋白质分泌和热应激作出反应。在相同的分泌压力条件下,与野生型相比,cssS突变体的转录组图谱分析显示,一些基因以CssRS依赖性方式改变了转录,例如citM,ylxF,yloA,ykoJ和flgB操纵子。但是,仅对htrA,htrB和citM观察到高亲和力的CssR结合。此外,DNA宏阵列方法揭示了孢子形成途径的几个基因被AmyQ过表达下调,并且一组运动特异性(依赖sigmaD的)转录物明显上调。随后的流式细胞仪分析表明,当AmyQ以及α-淀粉酶的不可分泌变体过量生产时,孢子形成过程将受到严重抑制。进行了类似的实验,以研究hag启动子的表达水平,hag启动子是sigmaD依赖性基因表达的公认报告子。这种方法证实了基于我们的DNA宏阵列分析的观察结果,并导致我们得出结论,在所有α-淀粉酶过量生产的条件下,与运动相关的几个基因的表达水平均维持在较高水平。
  • 【基于网络的工作场所健康促进计划的现场测试,以改善饮食习惯,减轻压力和增加体育锻炼:随机对照试验。】 复制标题 收藏 收藏
    DOI:10.2196/jmir.9.2.e17 复制DOI
    作者列表:Cook RF,Billings DW,Hersch RK,Back AS,Hendrickson A
    BACKGROUND & AIMS: BACKGROUND:Most work sites engage in some form of health promotion programming designed to improve worker health and reduce health care costs. Although these programs have typically been delivered through combinations of seminars and print materials, workplace health promotion programs are increasingly being delivered through the Internet. OBJECTIVE:The purpose of this research was to evaluate the effectiveness of a Web-based multimedia health promotion program for the workplace, designed to improve dietary practices, reduce stress, and increase physical activity. METHODS:Using a randomized controlled trial design with pretest-posttest comparisons within each group, 419 employees of a human resources company were randomly assigned to the Web-based condition or to a condition that provided print materials on the same topics. All subjects were assessed at pretest and posttest through an online questionnaire containing multiple measures of health behavior and attitudes. The test period was 3 months. Questionnaire data were analyzed mainly by analysis of covariance and t tests. RESULTS:Retention rates were good for both groups-85% for the Web-based group and 87% for the print group. Subjects using the Web-based program performed significantly better than the print group on Attitudes Toward a Healthful Diet (F(1,415) = 7.104, P = .008) and Dietary Stage of Change (F(1,408) = 6.487, P = .01), but there were no significant group differences on the five other dietary measures. Both groups also showed improvement from pretest to posttest on most dietary measures, as indicated by significant t tests. Within the Web-based group, dosage analyses showed significant effects of the number of times the subject accessed the program on measures of Dietary Self-Efficacy (F(2,203) = 5.270, P = .003), Attitudes Toward a Healthful Diet (F(2,204) = 2.585, P = .045), and Dietary Stage of Change (F(2,200) = 4.627, P = .005). No significant differences were found between the two groups on measures of stress or physical activity, although t tests of pretest-posttest changes indicated that both groups improved on several of these measures. The Web-based group gave significantly higher ratings to the program materials than the print group on all health topics and in their overall evaluation (F(1,410) = 9.808, P = .002). CONCLUSIONS:The Web-based program was more effective than print materials in producing improvements in the areas of diet and nutrition but was not more effective in reducing stress or increasing physical activity. The higher ratings given to the Web-based program suggest that workers preferred it to the print materials. Both groups showed numerous pretest-posttest improvements in all health topics, although such improvements might be attributable in part to a Hawthorne effect. Results suggest that a multimedia Web-based program can be a promising means of delivering health promotion material to the workforce, particularly in the area of diet and nutrition.
    背景与目标: 背景:大多数工作场所都参与某种形式的健康促进计划,旨在改善工人的健康状况并降低医疗成本。尽管这些程序通常是通过研讨会和印刷材料的组合来交付的,但工作场所健康促进程序正越来越通过Internet交付。
    目的:本研究的目的是评估针对工作场所的基于Web的多媒体健康促进计划的有效性,该计划旨在改善饮食习惯,减轻压力并增加体育锻炼。
    方法:使用在每个组中进行前测后测比较的随机对照试验设计,将419名人力资源公司的员工随机分配到基于Web的条件或提供相同主题印刷材料的条件。通过在线问卷对所有受试者进行测试前和测试后评估,该问卷包含健康行为和态度的多种测量。测试期为3个月。问卷数据主要通过协方差分析和t检验进行分析。
    结果:两组的保留率均良好,基于Web的组的保留率为85%,而印刷组的保留率为87%。使用基于Web的程序的受试者的表现明显优于印刷组的“对健康饮食的态度(F(1,415)= 7.104,P = .008)”和“饮食变化阶段”(F(1,408)= 6.487,P = 0.01)。 ),但其他五种饮食措施之间没有显着的群体差异。正如显着的t检验所示,两组在大多数饮食措施上均显示从测试前到测试后的改善。在基于网络的小组中,剂量分析显示受试者访问该计划的次数对饮食自我效能的测量具有显着影响(F(2,203)= 5.270,P = .003),对健康饮食的态度(F (2,204)= 2.585,P = .045)和饮食变化阶段(F(2,200)= 4.627,P = .005)。两组之间在压力或身体活动的测量上没有发现显着差异,尽管前测-后测变化的t检验表明,两组在其中一些测量上均有改善。在所有健康主题及其总体评估中,基于网络的小组对计划材料的评分均比印刷小组高得多(F(1,410)= 9.808,P = .002)。
    结论:基于Web的程序在饮食和营养方面的改进比印刷材料更有效,但在减轻压力或增加体育锻炼方面却没有更有效。基于Web的程序获得的较高评级表明,工人更喜欢它而不是印刷材料。两组在所有健康主题上均表现出无数的测试前-测试后改善,尽管这种改善可能部分归因于霍桑效应。结果表明,基于多媒体Web的程序可以成为向员工提供健康促进材料的有前途的手段,特别是在饮食和营养领域。
  • 【整株植物的响应,关键过程以及对干旱胁迫的适应性:以水稻为例。】 复制标题 收藏 收藏
    DOI:10.1093/jxb/erl101 复制DOI
    作者列表:Lafitte HR,Yongsheng G,Yan S,Li ZK
    BACKGROUND & AIMS: :Most high-yielding rice cultivars developed for irrigated conditions, including the widely grown lowland variety IR64, are highly susceptible to drought stress. This limits their adoption in rainfed rice environments where there is a risk of water shortage during the growing season. Mapping studies using lowland-by-upland rice populations have provided limited information about the genetic basis of variation in yield under drought. One approach to simultaneously improve and understand rice drought tolerance is to generate backcross populations, select superior lines in managed stress environments, and then evaluate which features of the selected lines differ from the recurrent parent. This approach was been taken with IR64, using a range of tolerant and susceptible cultivars as donor parents. Yields of the selected lines measured across 13 widely contracting water environments were generally greater than IR64, but genotype-by-environment effects were large. Traits expected to vary between IR64 and selected lines are plant height, because many donors were not semi-dwarf types, and maturity, because selection in a terminal stress environment is expected to favour earliness. In these experiments it was found that some lines that performed better under upland drought were indeed taller than IR64, but that shorter lines with good yield under drought could also be identified. In trials where drought stress developed in previously flooded (lowland) fields, height was not associated with performance. There was little change in maturity with selection. Other notable differences between IR64 and the selected backcross lines were in their responses to applied ABA and ethylene in greenhouse experiments at the vegetative stage and in leaf rolling observed under chronic upland stress in the field. These observations are consistent with the hypothesis that adaptive responses to drought can effectively allow for improved performance across a broad range of water environments. The results indicate that the yield of IR64 under drought can be significantly improved by backcrossing with selection under stress. In target environments where drought is infrequent but significant in certain years, improved IR64 with greater drought tolerance would be a valuable option for farmers.
    背景与目标: :大多数为灌溉条件开发的高产水稻品种,包括广泛种植的低地品种IR64,极易受到干旱胁迫的影响。这限制了它们在雨育稻米环境中的采用,在雨育水稻环境中,生长期存在缺水的风险。使用低陆旱稻群体进行的作图研究提供了有关干旱条件下产量变化的遗传基础的有限信息。同时提高和了解水稻耐旱性的一种方法是生成回交群体,在有控制的胁迫环境中选择优良品系,然后评估所选品系的哪些特征与轮回亲本不同。 IR64采用了这种方法,使用了一系列耐性和易感品种作为供体亲本。在13个广泛收缩的水环境中测得的选定品系的产量通常高于IR64,但基因型对环境的影响很大。预期在IR64和选定品系之间变化的性状是植物高度,因为许多供体不是半矮型,而成熟则是因为在终极胁迫环境中选择有利于早熟。在这些实验中,发现一些在陆地干旱条件下表现更好的品系确实比IR64高,但也可以鉴定出在干旱条件下具有良好产量的较短品系。在先前淹没的(低地)田地中出现干旱胁迫的试验中,身高与体能没有关系。选择的成熟度几乎没有变化。 IR64和所选回交系之间的其他显着差异在于,在植物生长阶段的温室试验以及田间在长期高地胁迫下观察到的卷叶过程中,它们对施用的ABA和乙烯的反应。这些观察结果与以下假设相吻合:对干旱的适应性反应可以有效地在广泛的水环境中改善性能。结果表明,干旱条件下回交与选育可以显着提高干旱条件下IR64的产量。在很少发生干旱但在某些年份发生严重干旱的目标环境中,提高IR64耐旱性将是农民的一个宝贵选择。
  • 【预先存在的炎性状态损害了暴露于热应激的大鼠的耐热性。】 复制标题 收藏 收藏
    DOI:10.1152/ajpregu.00921.2005 复制DOI
    作者列表:Lim CL,Wilson G,Brown L,Coombes JS,Mackinnon LT
    BACKGROUND & AIMS: :This study investigated the roles of endotoxemia and heat-induced tissue damage in the pathology of heat stroke. In groups of eight, male Wistar rats were treated with heat exposure only (HE), or heat exposure with turpentine (T+HE), dexamethasone (D+HE), and turpentine and dexamethasone combined (TD+HE). The rats remained sedated for 2 h after receiving the respective treatments, followed by heat exposure until the core temperature (T(c)) was 42 degrees C for 15 min; control rats received turpentine (T), dexamethasone (D), and turpentine and dexamethasone (TD) without heat stress. Blood samples were collected before treatment (baseline I), after 2 h of passive rest (baseline II), at T(c) 40 degrees C (T40), and 15 min after achieving T(c) 42 degrees C (T42). No rats died in the nonheat-stressed groups. Survival rate was lowest in the TD+HE rats (37.5%), followed by the HE (62.5%), T+HE (75%), and D+HE (100%) rats (P < 0.05). The duration of survival at T42 degrees C was shortest in the TD+HE rats (9.9 +/- 6.2 min) (P < 0.01), followed by the T+HE (11.3 +/- 6.1 min) and the HE (12.2 +/- 4 min) (P < 0.05) rats. The increase in plasma IL-6 concentrations was highest in the T+HE (352%) and HE (178%) rats (P < 0.05). D+HE treatment suppressed the increases in plasma aspartate transaminase, alanine aminotransferase, and IL-6 and LPS concentrations during severe heat stress. Heat stroke can be triggered by endotoxemia or heat-induced tissue damage, and preexisting inflammation compromises heat tolerance, whereas blocking endotoxemia increases heat tolerance.
    背景与目标: :这项研究调查了内毒素血症和热诱导的组织损伤在中暑病理中的作用。在八只一组中,雄性Wistar大鼠仅接受热暴露(HE),或采用松节油(T HE),地塞米松(D HE)以及松节油和地塞米松联合治疗(TD HE)进行治疗。在接受相应的治疗后,大鼠保持镇静状态2小时,然后进行热暴露,直到核心温度(T(c))为42摄氏度持续15分钟;对照组大鼠接受松节油(T),地塞米松(D),松节油和地塞米松(TD),无热应激。在治疗前(基线I),被动休息2小时(基线II),T(c)40摄氏度(T40)和达到T(c)42摄氏度(T42)15分钟后收集血样。在非热应激组中没有大鼠死亡。在TD HE大鼠中,成活率最低(37.5%),其次是HE(62.5%),T HE(75%)和DHE(100%)(P <0.05)。 TD HE大鼠在T42摄氏度下的生存时间最短(9.9 /-6.2分钟)(P <0.01),其次是T HE(11.3 /-6.1分钟)和HE(12.2 /-4分钟) (P <0.05)大鼠。在T HE(352%)和HE(178%)大鼠中,血浆IL-6浓度的增加最高(P <0.05)。在严重的热应激条件下,D HE治疗抑制了血浆天冬氨酸转氨酶,丙氨酸转氨酶以及IL-6和LPS浓度的增加。内毒素血症或热引起的组织损伤可引发中暑,既往炎症会损害耐热性,而阻断内毒素血症则会增加耐热性。

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