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691.
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
692.
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
693.
The developmental dynamics of the maize leaf transcriptome 总被引:5,自引:0,他引:5
694.
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
695.
de Oliveira JC 《Studies in history and philosophy of science》2012,43(1):115-121
In this paper I identify a tension between the two sets of works by Kuhn regarding the genesis of the "new historiography of science". In the first, it could be said that the change from the traditional to the new historiography is strictly endogenous (referring to internal causes or reasons). In the second, the change is predominantly exogenous. To address this question, I draw on a text that is considered to be less important among Kuhn's works, but which, as shall be argued, allows some contact between Kuhn's two approaches via Koyré. I seek to point out and differentiate the roles of Koyré and Kuhn--from Kuhn's point of view--in the development of the historiography of science and, as a complement, present some reflections regarding the justification of the new historiography. 相似文献
696.
Gauthier LR Granotier C Hoffschir F Etienne O Ayouaz A Desmaze C Mailliet P Biard DS Boussin FD 《Cellular and molecular life sciences : CMLS》2012,69(4):629-640
Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways.
Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere
conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different
cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the
G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses
and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere
fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands.
NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere
fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during
mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting
by the G-quadruplex ligand 360A, leading to cancer cell death. 相似文献
697.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献
698.
Although all nucleated cells within a multicellular organism contain a complete copy of the genome, cell identity relies on
the expression of a specific subset of genes. Therefore, when cells divide they must not only copy their genome to their daughters,
but also ensure that the pattern of gene expression present before division is restored. While the carrier of this epigenetic
memory has been a topic of much research and debate, post-translational modifications of histone proteins have emerged in
the vanguard of candidates. In this paper we examine the mechanisms by which histone post-translational modifications are
propagated through DNA replication and cell division, and we critically examine the evidence that they can also act as vectors
of epigenetic memory. Finally, we consider ways in which epigenetic memory might be disrupted by interfering with the mechanisms
of DNA replication. 相似文献
699.
Valiokas R 《Cellular and molecular life sciences : CMLS》2012,69(3):347-356
The actual progress towards biological chip devices consisting of nanostructured functional entities is summarized. The practical
aspects of molecular nanobiochips are discussed, including the main surface chemistry platforms, as well as conventional and
unconventional fabrication tools. Several successful biological demonstrations of the first generation of nanobiochip devices
(mainly, different nanoarrays) are highlighted with the aim of revealing the potential of this technology in life sciences,
medicine, and related areas. 相似文献
700.
Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune
response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement
of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and
chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released
from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated
in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can
initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize
the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous
TLR ligands in the tumorigenesis. 相似文献