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141.
Lindahl E Nyman U Melles E Sigmundsson K Ståhlberg M Wahren J Obrink B Shafqat J Joseph B Jörnvall H 《Cellular and molecular life sciences : CMLS》2007,64(4):479-486
Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is
internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide,
we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport
into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at
4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive
mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated
binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components
to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence
of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that
of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.
Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006 相似文献
142.
石墨烯(GN)是一种新型的二维材料,是增强高分子复合材料的理想填料.采用液相剥离法(LPE),选择十二烷基硫酸钠(SDS)以及十二烷基苯磺酸钠(SDBS)为表面活性剂,制备了少层GN,对比了SDS及SDBS的剥离GN的效果.进一步,通过熔融共混法制备了高性能GN/PA6复合材料,研究了不同添加量的GN对PA6力学性能的影响.结果表明:SDBS有更好的剥离效果,当SDBS质量浓度为10 mg/mL时,通过超声剥离6 h,可得质量浓度为0.37 mg/mL的石墨烯分散液.当GN添加量为0.3%时,断裂强度达到最大值,比纯PA6提高了29.9%. 相似文献
143.
褚项宁 濮祖荫 曹馨 V.MISHIN 王珏 魏勇 宗秋刚 傅绥燕 谢伦 V.ANGELOPOULOS 刘江 K.H.GLASSMEIER J.MCFADDEN D.LARSON S.MENDE H.FREY C.T.RUSSELL I.MANN D.SIBECK T.I.SAIFUDINOVA M.V.TOLOCHKO L.A.SAPRONOVA H.REME E.LUCEK 《中国科学:技术科学》2010,(5):565-574
本文利用THEMIS卫星结合地面极光和地磁的观测,研究了2008年2月26日04:05和04:55UT的两次亚暴事件.Angelopoulos已经对发生在04:55UT的第二个亚暴事件做了分析.本文对两次亚暴的相关活动进行了详细研究,特别对第一次做了深入讨论,并着重分析了磁重联与亚暴活动的关系.在两次亚暴的初始阶段,第一次极光增亮发生在中磁尾磁重联后2~3min,但是持续时间较短,极向膨胀缓慢,与伪暴的特征相似,标志了亚暴的初突发(initial onset).两次亚暴都存在第二次极光增亮和极光的极向膨胀,且时间与近地磁尾观测的地向流和磁场偶极化同时发生,并与亚暴膨胀相的其他活动的发生同步,标志了亚暴的主突发(major onset).在两次亚暴的增长相期间,极盖区开放磁通量持续增加;在亚暴膨胀相和恢复相中,极盖区磁通量迅速减少.表明两次亚暴膨胀相的演化分别与两次尾瓣开放磁力线重联过程相联系的.从亚暴活动的参数分析,这两次亚暴都属于小亚暴范围;从重联率分析,两次磁重联都属于弱重联.本文的观测结果表明,中磁尾磁尾重联首先触发伪暴;高速流将磁通量和能量传输到近地磁尾;高速流减速最终导致亚暴...更多电流楔(substorm current wedge,简称SCW)的形成和电流中断,产生近地偶极化和极光膨胀,引起亚暴膨胀相突发.本文的观测结果是对近地中性线模型(near earth neutral line,简称NENL)和重联-电流中断协同模型(synthesis scenario of MR and CD,简称RCS)模型及亚暴膨胀相两步突发观点的有力支持. 相似文献
144.
地球磁尾电流片拍动的起源和运动方式一直是磁尾动力学研究中的重要问题之一.本文利用Cluster卫星数据,统计分析了2001年和2003年的磁尾电流片运动特性,利用我们最近发展的分析结构特征方向和运动速度的新方法,计算了磁尾电流片的运动速度,并给出了磁尾电流片在GSE坐标系中XY平面内的速度分布图.我们发现磁尾电流片存在着两种不同性质的运动,除了磁尾电流片向晨昏方向的运动,分析表明,磁尾电流片还存在着明显朝向子夜方向的运动(即GSE坐标系中Y=0平面).观测还进一步表明,位于磁尾中间区域(|Y_GSE|〈8Re)的电流片的扰动,其南北向的速度分量相对较大,这从另一个方面说明磁尾中性片的中间区域可能是导致大部分磁尾电流片拍动事件中电流片朝向晨昏两侧运动的源区.对于运动方向朝向子夜方向(Y=0平面)的电流片,其运动方式与运动方向朝向晨昏两侧的电流片存在着明显的不同,因此我们推测,它们应具有不同的起源.本文的统计结果,为我们深入研究地球磁尾电流片拍动源区等物理问题提供了的参考依据. 相似文献
145.
Haack TB Danhauser K Haberberger B Hoser J Strecker V Boehm D Uziel G Lamantea E Invernizzi F Poulton J Rolinski B Iuso A Biskup S Schmidt T Mewes HW Wittig I Meitinger T Zeviani M Prokisch H 《Nature genetics》2010,42(12):1131-1134
An isolated defect of respiratory chain complex I activity is a frequent biochemical abnormality in mitochondrial disorders. Despite intensive investigation in recent years, in most instances, the molecular basis underpinning complex I defects remains unknown. We report whole-exome sequencing of a single individual with severe, isolated complex I deficiency. This analysis, followed by filtering with a prioritization of mitochondrial proteins, led us to identify compound heterozygous mutations in ACAD9, which encodes a poorly understood member of the mitochondrial acyl-CoA dehydrogenase protein family. We demonstrated the pathogenic role of the ACAD9 variants by the correction of the complex I defect on expression of the wildtype ACAD9 protein in fibroblasts derived from affected individuals. ACAD9 screening of 120 additional complex I-defective index cases led us to identify two additional unrelated cases and a total of five pathogenic ACAD9 alleles. 相似文献
146.
Morelli G Song Y Mazzoni CJ Eppinger M Roumagnac P Wagner DM Feldkamp M Kusecek B Vogler AJ Li Y Cui Y Thomson NR Jombart T Leblois R Lichtner P Rahalison L Petersen JM Balloux F Keim P Wirth T Ravel J Yang R Carniel E Achtman M 《Nature genetics》2010,42(12):1140-1143
Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs. 相似文献
147.
Hüffmeier U Uebe S Ekici AB Bowes J Giardina E Korendowych E Juneblad K Apel M McManus R Ho P Bruce IN Ryan AW Behrens F Lascorz J Böhm B Traupe H Lohmann J Gieger C Wichmann HE Herold C Steffens M Klareskog L Wienker TF Fitzgerald O Alenius GM McHugh NJ Novelli G Burkhardt H Barton A Reis A 《Nature genetics》2010,42(11):996-999
Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV. 相似文献
148.
Over the last two decades the molecular and cellular mechanisms underlying T cell activation, expansion, differentiation,
and memory formation have been intensively investigated. These studies revealed that the generation of memory T cells is critically
impacted by a number of factors, including the magnitude of the inflammatory response and cytokine production, the type of
dendritic cell [DC] that presents the pathogen derived antigen, their maturation status, and the concomitant provision of
costimulation. Nevertheless, the primary stimulus leading to T cell activation is generated through the T cell receptor [TCR]
following its engagement with a peptide MHC ligand [pMHC]. The purpose of this review is to highlight classical and recent
findings on how antigen recognition, the degree of TCR stimulation, and intracellular signal transduction pathways impact
the formation of effector and memory T cells. 相似文献
149.
Regenerating functional heart tissue for myocardial repair 总被引:1,自引:1,他引:0
Alcon A Cagavi Bozkulak E Qyang Y 《Cellular and molecular life sciences : CMLS》2012,69(16):2635-2656
Heart disease is one of the leading causes of death worldwide and the number of patients with the disease is likely to grow with the continual decline in health for most of the developed world. Heart transplantation is one of the only treatment options for heart failure due to an acute myocardial infarction, but limited donor supply and organ rejection limit its widespread use. Cellular cardiomyoplasty, or cellular implantation, combined with various tissue-engineering methods aims to regenerate functional heart tissue. This review highlights the numerous cell sources that have been used to regenerate the heart as well as cover the wide range of tissue-engineering strategies that have been devised to optimize the delivery of these cells. It will probably be a long time before an effective regenerative therapy can make a serious impact at the bedside. 相似文献
150.
Ebstein F Kloetzel PM Krüger E Seifert U 《Cellular and molecular life sciences : CMLS》2012,69(15):2543-2558
The proteasome is a multi-catalytic protein complex whose primary function is the degradation of abnormal or foreign proteins. Upon exposure of cells to interferons (IFNs), the β1i/LMP2, β2i/MECL-1, and β5i/LMP7 subunits are induced and incorporated into newly synthesized immunoproteasomes (IP), which are thought to function solely as critical players in the optimization of the CD8(+) T-cell response. However, the observation that IP are present in several non-immune tissues under normal conditions and/or following pathological events militates against the view that its role is limited to MHC class I presentation. In support of this concept, the recent use of genetic models deficient for β1i/LMP2, β2i/MECL-1, or β5i/LMP7 has uncovered unanticipated functions for IP in innate immunity and non-immune processes. Herein, we review recent data in an attempt to clarify the role of IP beyond MHC class I epitope presentation with emphasis on its involvement in the regulation of protein homeostasis, cell proliferation, and cytokine gene expression. 相似文献