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排序方式: 共有166条查询结果,搜索用时 828 毫秒
131.
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Werner E. G. Müller Maximilian Ackermann Shunfeng Wang Meik Neufurth Rafael Muñoz-Espí Qingling Feng Heinz C. Schröder Xiaohong Wang 《Cellular and molecular life sciences : CMLS》2018,75(1):21-32
In this study, the effect of inorganic polyphosphate (polyP) on the initial phase of angiogenesis and vascularization was investigated, applying the HUVEC cell tube formation assay. PolyP is a physiological and high energy phosphate polymer which has been proposed to act as a metabolic fuel in the extracellular space with only a comparably low ATP content. The experiments revealed that polyP accelerates tube formation of human umbilical vein endothelial cells (HUVEC), seeded onto a solidified basement membrane extract matrix which contains polyP-metabolizing alkaline phosphatase (ALP) activity. This effect is abolished by co-addition of apyrase, which degrades ATP to AMP and inorganic phosphate. The assumption that ATP, derived from polyP, activates HUVEC cells leading to tube formation was corroborated by experiments showing that addition of polyP to the cells causes a strong rise of ATP level in the culture medium. Finally, we show that at a later stage of cultivation of HUVEC cells, after 3 d, polyP causes a strong enhancement of the expression of the genes encoding for the two major matrix metalloproteinases (MMPs) released by endothelial cells during tube formation, MMP-9 and MMP-2. This stimulatory effect is again abrogated by addition of apyrase together with polyP. From these results, we propose that polyP is involved either directly or indirectly in energy supply, via ALP-mediated transfer of energy-rich phosphate under ATP formation. This ATP is utilized for the activation and oriented migration of endothelial cells and for the matrix organization during the initial phases of tube formation. 相似文献
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Vogt J Glumm R Schlüter L Schmitz D Rost BR Streu N Rister B Suman Bharathi B Gagiannis D Hildebrandt H Weinhold B Mühlenhoff M Naumann T Savaskan NE Brauer AU Reutter W Heimrich B Nitsch R Horstkorte R 《Cellular and molecular life sciences : CMLS》2012,69(7):1179-1191
During development, axonal projections have a remarkable ability to innervate correct dendritic subcompartments of their target neurons and to form regular neuronal circuits. Altered axonal targeting with formation of synapses on inappropriate neurons may result in neurodevelopmental sequelae, leading to psychiatric disorders. Here we show that altering the expression level of the polysialic acid moiety, which is a developmentally regulated, posttranslational modification of the neural cell adhesion molecule NCAM, critically affects correct circuit formation. Using a chemically modified sialic acid precursor (N-propyl-D: -mannosamine), we inhibited the polysialyltransferase ST8SiaII, the principal enzyme involved in polysialylation during development, at selected developmental time-points. This treatment altered NCAM polysialylation while NCAM expression was not affected. Altered polysialylation resulted in an aberrant mossy fiber projection that formed glutamatergic terminals on pyramidal neurons of the CA1 region in organotypic slice cultures and in vivo. Electrophysiological recordings revealed that the ectopic terminals on CA1 pyramids were functional and displayed characteristics of mossy fiber synapses. Moreover, ultrastructural examination indicated a "mossy fiber synapse"-like morphology. We thus conclude that homeostatic regulation of the amount of synthesized polysialic acid at specific developmental stages is essential for correct synaptic targeting and circuit formation during hippocampal development. 相似文献
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Wiesner T Obenauf AC Murali R Fried I Griewank KG Ulz P Windpassinger C Wackernagel W Loy S Wolf I Viale A Lash AE Pirun M Socci ND Rütten A Palmedo G Abramson D Offit K Ott A Becker JC Cerroni L Kutzner H Bastian BC Speicher MR 《Nature genetics》2011,43(10):1018-1021
Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm. 相似文献
136.
Xu B Roos JL Dexheimer P Boone B Plummer B Levy S Gogos JA Karayiorgou M 《Nature genetics》2011,43(9):864-868
Despite its high heritability, a large fraction of individuals with schizophrenia do not have a family history of the disease (sporadic cases). Here we examined the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exomes of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 cases affecting 40 genes, including a potentially disruptive mutation in DGCR2, a gene located in the schizophrenia-predisposing 22q11.2 microdeletion region. A comparison to rare inherited variants indicated that the identified de novo mutations show a large excess of non-synonymous changes in schizophrenia cases, as well as a greater potential to affect protein structure and function. Our analyses suggest a major role for de novo mutations in schizophrenia as well as a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease. 相似文献
137.
Schormair B Kemlink D Roeske D Eckstein G Xiong L Lichtner P Ripke S Trenkwalder C Zimprich A Stiasny-Kolster K Oertel W Bachmann CG Paulus W Högl B Frauscher B Gschliesser V Poewe W Peglau I Vodicka P Vávrová J Sonka K Nevsimalova S Montplaisir J Turecki G Rouleau G Gieger C Illig T Wichmann HE Holsboer F Müller-Myhsok B Meitinger T Winkelmann J 《Nature genetics》2008,40(8):946-948
We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS. 相似文献
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We show that the phase velocity in a stationary state of a de Broglie wave can be directly obtained from the probability distribution, i.e. the quantum trajectories, without detailed knowledge of the phase term itself. In other words, the amplitude of a de Broglie wave function describes not only the probability distribution but also the phase velocity distribution. Using this relationship, we comment on two calculations of the Goos-H nchen shift in de Broglie waves. 相似文献