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31.
A. F. Vanin L. M. Bevers A. Slama-Schwok E. E. van Faassen 《Cellular and molecular life sciences : CMLS》2008,65(24):4066-4069
Announcement
Announcement 相似文献32.
33.
Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively approximately 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease. 相似文献
34.
Horlings HM Bergamaschi A Nordgard SH Kim YH Han W Noh DY Salari K Joosse SA Reyal F Lingjaerde OC Kristensen VN Børresen-Dale AL Pollack J van de Vijver MJ 《Nature genetics》2008,40(7):809; author reply 810-809; author reply 812
35.
van Es MA van Vught PW Blauw HM Franke L Saris CG Van den Bosch L de Jong SW de Jong V Baas F van't Slot R Lemmens R Schelhaas HJ Birve A Sleegers K Van Broeckhoven C Schymick JC Traynor BJ Wokke JH Wijmenga C Robberecht W Andersen PM Veldink JH Ophoff RA van den Berg LH 《Nature genetics》2008,40(1):29-31
We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies. 相似文献
36.
This article discusses the quest for the mechanical advantage of the wedge in the eighteenth century. As a case study, the wedge enlightens our understanding of eighteenth-century mechanics in general and the controversy over “force” or vis viva in particular. In this article, I show that the two different approaches to mechanics, the one that favoured force in terms of velocities and the one that primarily used displacements—known as the ‘Newtonian’ and ‘Leibnizian’ methods, respectively—were not at all on par in their ability to solve the problem of the wedge. In general, only those who used the Leibnizian concept of force or some related notion were able to get to the conventional results. This article thus rebuts the received view that the vis viva controversy was merely a semantic one. Instead, it shows that different understandings of “force” led to real and pragmatic differences in eighteenth-century mechanics. 相似文献
37.
Marij van Strien 《Annals of science》2013,70(3):381-400
During the period 1860–1880, a number of physicists and mathematicians, including Maxwell, Stewart, Cournot and Boussinesq, used theories formulated in terms of physics to argue that the mind, the soul or a vital principle could have an impact on the body. This paper shows that what was primarily at stake for these authors was a concern about the irreducibility of life and the mind to physics, and that their theories can be regarded primarily as reactions to the law of conservation of energy, which was used among others by Helmholtz and Du Bois-Reymond as an argument against the possibility of vital and mental causes in physiology. In light of this development, Maxwell, Stewart, Cournot and Boussinesq showed that it was still possible to argue for the irreducibility of life and the mind to physics, through an appeal to instability or indeterminism in physics: if the body is an unstable or physically indeterministic system, an immaterial principle can act through triggering or directing motions in the body, without violating the laws of physics. 相似文献
38.
Experimental modeling is the construction of theoretical models hand in hand with experimental activity. As explained in Section 1, experimental modeling starts with claims about phenomena that use abstract concepts, concepts whose conditions of realization are not yet specified; and it ends with a concrete model of the phenomenon, a model that can be tested against data. This paper argues that this process from abstract concepts to concrete models involves judgments of relevance, which are irreducibly normative. In Section 2, we show, on the basis of several case studies, how these judgments contribute to the determination of the conditions of realization of the abstract concepts and, at the same time, of the quantities that characterize the phenomenon under study. Then, in Section 3, we compare this view on modeling with other approaches that also have acknowledged the role of relevance judgments in science. To conclude, in Section 4, we discuss the possibility of a plurality of relevance judgments and introduce a distinction between locally and generally relevant factors. 相似文献
39.
Géza Tamás Szabó Bettina Tarr Krisztina Pálóczi Katalin Éder Eszter Lajkó Ágnes Kittel Sára Tóth Bence György Mária Pásztói Andrea Németh Xabier Osteikoetxea Éva Pállinger András Falus Katalin Szabó-Taylor Edit Irén Buzás 《Cellular and molecular life sciences : CMLS》2014,71(20):4055-4067
Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time. 相似文献
40.
Daniel Tarrant Tobias von der Haar 《Cellular and molecular life sciences : CMLS》2014,71(21):4195-4206
Quantitative control of gene expression occurs at multiple levels, including the level of translation. Within the overall process of translation, most identified regulatory processes impinge on the initiation phase. However, recent studies have revealed that the elongation phase can also regulate translation if elongation and initiation occur with specific, not mutually compatible rate parameters. Translation elongation then limits the overall amount of protein that can be made from an mRNA. Several recently discovered control mechanisms of biological pathways are based on such elongation control. Here, we review the molecular mechanisms that determine ribosome speed in eukaryotic organisms, and discuss under which conditions ribosome speed can become the controlling parameter of gene expression levels. 相似文献