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排序方式: 共有256条查询结果,搜索用时 46 毫秒
101.
Tia DiTommaso Lynelle K. Jones Denny L. Cottle The WTSI Mouse Genetics Program Anna-Karin Gerdin Valerie E. Vancollie Fiona M. Watt Ramiro Ramirez-Solis Allan Bradley Karen P. Steel John P. Sundberg Jacqueline K. White Ian M. Smyth 《PLoS genetics》2014,10(10)
The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute''s Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation. 相似文献
102.
Zequn Jiang Funding This work was supported by grants from the National Natural Science Foundation of China and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions PAPD.Weiping Chen Xiaojing Yan Lei Bi Sheng Guo Zhen Zhan 《Acta biochimica et biophysica Sinica》2014,(5):357-367
Paeoniflorin (PF) is one of the main effective components extracted from the root of Paeonia lactiflora, which has been used clinically to treat hepatitis in traditional Chinese medicine, but the details of the underlying mechanism remain unknown. The present study was designed to investigate the mechanism of protective effect of PF on d-galactosamine (GalN) and tumor necrosis factor-α (TNF-α)-induced cell apoptosis using human L02 hepatocytes. Our results confirmed that PF could attenuate GalN/TNF-α-induced apoptotic cell death in a dose-dependent manner. The disruption of mitochondrial membrane potential and the disturbance of intracellular Ca2+ concentration were also recovered by PF. Western blot analysis revealed that GalN/TNF-α induced the activation of a number of signature endoplasmic reticulum (ER) stress and mitochondrial markers, while PF pre-treatment had a marked dose-dependent suppression on them. Additionally, the anti-apoptotic effect of PF was further evidenced by the inhibition of caspase-3/9 activities in L02 cells. These findings suggest that PF can effectively inhibit hepatocyte apoptosis and the underlying mechanism is related to the regulating mediators in ER stress and mitochondria-dependent pathways. 相似文献
103.
鳄蜥的食物识别机制 总被引:1,自引:0,他引:1
鳄蜥(Shinisaurus crocodilurus)食物识别机制的研究,对进一步了解鳄蜥的捕食行为和生态学习性有重要意义。使用棉棒分别沾上去离子水、香水、黄粉虫(Tenebriomolitor L.)和蚯蚓(Pheretima sp.)的气味(蚯蚓和黄粉虫处死后绞碎以便于棉花棒蘸上),观察11只鳄蜥对4种化学刺激的反应,每个个体对每种刺激均进行24次实验重复。实验结果显示:鳄蜥对4种刺激均有反应,对黄粉虫和蚯蚓刺激的舔舌次数显著高于香水和去离子水的舔舌次数(Wilcoxon test,所有P<0.001),表明鳄蜥能检测以及识别控制刺激和食物刺激。再又对鳄蜥进行4种处理实验:(A)空白对照;(B)蚯蚓气味;(C)密封着的活蚯蚓;(D)活蚯蚓。每个个体每种处理均进行5次实验。结果显示:鳄蜥在不同处理下的行为持续时间、探究频次和攻击频次有显著差异(Friedman test,所有P<0.001)。鳄蜥在仅有视觉刺激出现的处理C以及既有化学刺激又有视觉刺激的处理D比仅有化学刺激的处理B在持续时间、探究频次和攻击频次上显著要高(所有P<0.001)。在无视觉刺激的条件下,鳄蜥在处理B的行为持续时间以及探究频次均显著高于处理A 的(所有P<0.001);而在视觉信息相同的条件下,鳄蜥在处理D中仅行为持续时间显著高于处理C(Z=3.95, P<0.001),而探究频次以及攻击频次无显著差异(前者Z=1.53, P=0.13;后者Z=1.10, P=0.27)。结果表明鳄蜥主要利用视觉捕食,化学感觉有辅助作用。鳄蜥这种食物识别机制可能与捕食模式和种系发生有关,也可能受食物的影响。 相似文献
104.
105.
Olufsen MS Tran HT Ottesen JT;Research Experiences for Undergraduates Program Lipsitz LA Novak V 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,291(5):R1355-R1368
During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key role in maintaining arterial pressure by regulating heart rate. This study presents a mathematical model that can predict the dynamics of heart rate regulation in response to postural change from sitting to standing. The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse least squares problem for parameter estimation and successfully demonstrate that our mathematical model can accurately predict heart rate dynamics observed in data obtained from healthy young, healthy elderly, and hypertensive elderly subjects. One of our key findings indicates that, to successfully validate our model against clinical data, it is necessary to include the vestibulo-sympathetic reflex. Furthermore, our model reveals that the transfer between the nerve firing and blood pressure is nonlinear and follows a hysteresis curve. In healthy young people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly people, the hysteresis loop shifts to higher blood pressure values, and its area is diminished. Finally, for hypertensive elderly people, the hysteresis loop is generally not closed, indicating that, during postural change from sitting to standing, baroreflex modulation does not return to steady state during the first minute of standing. 相似文献
106.
107.
Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci 总被引:1,自引:0,他引:1
Stitzel ML Sethupathy P Pearson DS Chines PS Song L Erdos MR Welch R Parker SC Boyle AP Scott LJ;NISC Comparative Sequencing Program Margulies EH Boehnke M Furey TS Crawford GE Collins FS 《Cell metabolism》2010,12(5):443-455
Identifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation modifications (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ~18,000 putative promoters (several hundred unannotated and islet-active). Surprisingly, active promoter modifications were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (nonpromoter) regulatory elements, 47% are islet unique and 22% are CTCF bound. In the 18 type 2 diabetes (T2D)-associated loci, we identified 118 putative regulatory elements and confirmed enhancer activity for 12 of 33 tested. Among six regulatory elements harboring T2D-associated variants, two exhibit significant allele-specific differences in activity. These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders. 相似文献
108.
Nancy Crum-Cianflone Mollie Poehlman Roediger Lynn Eberly Maryam Headd Vincent Marconi Anuradha Ganesan Amy Weintrob R. Vincent Barthel Susan Fraser Brian K. Agan the Infectious Disease Clinical Research Program HIV Working Group 《PloS one》2010,5(4)
Background
The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown.Methods
We evaluated prospective data from a U.S. Military HIV Natural History Study (1985–2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models.Results
Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era.Conclusions
HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care. 相似文献109.
McLaughlin HM Sakaguchi R Liu C Igarashi T Pehlivan D Chu K Iyer R Cruz P Cherukuri PF Hansen NF Mullikin JC;NISC Comparative Sequencing Program Biesecker LG Wilson TE Ionasescu V Nicholson G Searby C Talbot K Vance JM Züchner S Szigeti K Lupski JR Hou YM Green ED Antonellis A 《American journal of human genetics》2010,87(4):560-566
Charcot-Marie-Tooth (CMT) disease comprises a genetically and clinically heterogeneous group of peripheral nerve disorders characterized by impaired distal motor and sensory function. Mutations in three genes encoding aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT disease primarily associated with an axonal pathology. ARSs are ubiquitously expressed, essential enzymes responsible for charging tRNA molecules with their cognate amino acids. To further explore the role of ARSs in CMT disease, we performed a large-scale mutation screen of the 37 human ARS genes in a cohort of 355 patients with a phenotype consistent with CMT. Here we describe three variants (p.Leu133His, p.Tyr173SerfsX7, and p.Ile302Met) in the lysyl-tRNA synthetase (KARS) gene in two patients from this cohort. Functional analyses revealed that two of these mutations (p.Leu133His and p.Tyr173SerfsX7) severely affect enzyme activity. Interestingly, both functional variants were found in a single patient with CMT disease and additional neurological and non-neurological sequelae. Based on these data, KARS becomes the fourth ARS gene associated with CMT disease, indicating that this family of enzymes is specifically critical for axon function. 相似文献
110.
Ming Zhang Jia-Jin Zhuo Xu Wang Sen Wu Xiao-Feng Wang Key Laboratory for Genetics Breeding in Forest Trees Ornamental Plants Ministry of Education Beijing Forestry University Beijing China 《Acta Botanica Sinica》2010,(3)
This research was conducted to determine the optimum moisture content (MC) that gave maximum longevity to seeds. Three species were used to represent seeds with different dry matter reserves, which gives them different sorption properties: maize (Zea mays L.), elm (Ulmus pumila L.) and safflower (Carthamus tinctorius L.). The seeds of elm, safflower, and maize embryos with MC ranging from 0.00– 0.15 g H2O/g dry weight (DW) were stored at 35 °C for different periods of time. The results showed that the optim... 相似文献