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71.
Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters 总被引:5,自引:0,他引:5
72.
Chasman DI Schürks M Anttila V de Vries B Schminke U Launer LJ Terwindt GM van den Maagdenberg AM Fendrich K Völzke H Ernst F Griffiths LR Buring JE Kallela M Freilinger T Kubisch C Ridker PM Palotie A Ferrari MD Hoffmann W Zee RY Kurth T 《Nature genetics》2011,43(7):695-698
Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology. 相似文献
73.
Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease 总被引:1,自引:0,他引:1
Trynka G Hunt KA Bockett NA Romanos J Mistry V Szperl A Bakker SF Bardella MT Bhaw-Rosun L Castillejo G de la Concha EG de Almeida RC Dias KR van Diemen CC Dubois PC Duerr RH Edkins S Franke L Fransen K Gutierrez J Heap GA Hrdlickova B Hunt S Izurieta LP Izzo V Joosten LA Langford C Mazzilli MC Mein CA Midah V Mitrovic M Mora B Morelli M Nutland S Núñez C Onengut-Gumuscu S Pearce K Platteel M Polanco I Potter S Ribes-Koninckx C Ricaño-Ponce I Rich SS Rybak A Santiago JL Senapati S Sood A 《Nature genetics》2011,43(12):1193-1201
Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease. 相似文献
74.
van de Laar IM Oldenburg RA Pals G Roos-Hesselink JW de Graaf BM Verhagen JM Hoedemaekers YM Willemsen R Severijnen LA Venselaar H Vriend G Pattynama PM Collée M Majoor-Krakauer D Poldermans D Frohn-Mulder IM Micha D Timmermans J Hilhorst-Hofstee Y Bierma-Zeinstra SM Willems PJ Kros JM Oei EH Oostra BA Wessels MW Bertoli-Avella AM 《Nature genetics》2011,43(2):121-126
Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis. 相似文献
75.
Rai A Nöthe H Tzvetkov N Korenbaum E Manstein DJ 《Cellular and molecular life sciences : CMLS》2011,68(16):2751-2767
Dictyostelium discoideum cells produce five dynamin family proteins. Here, we show that dynamin B is the only member of this group of proteins that
is initially produced as a preprotein and requires processing by mitochondrial proteases for formation of the mature protein.
Our results show that dynamin B-depletion affects many aspects of cell motility, cell-cell and cell-surface adhesion, resistance
to osmotic shock, and fatty acid metabolism. The mature form of dynamin B mediates a wide range and unique combination of
functions. Dynamin B affects events at the plasma membrane, peroxisomes, the contractile vacuole system, components of the
actin-based cytoskeleton, and cell adhesion sites. The modulating effect of dynamin B on the activity of the contractile vacuole
system is unique for the Dictyostelium system. Other functions displayed by dynamin B are commonly associated with either classical dynamins or dynamin-related
proteins. 相似文献
76.
Biegel E Schmidt S González JM Müller V 《Cellular and molecular life sciences : CMLS》2011,68(4):613-634
Microbes have a fascinating repertoire of bioenergetic enzymes and a huge variety of electron transport chains to cope with
very different environmental conditions, such as different oxygen concentrations, different electron acceptors, pH and salinity.
However, all these electron transport chains cover the redox span from NADH + H+ as the most negative donor to oxygen/H2O as the most positive acceptor or increments thereof. The redox range more negative than −320 mV has been largely ignored.
Here, we have summarized the recent data that unraveled a novel ion-motive electron transport chain, the Rnf complex, that
energetically couples the cellular ferredoxin to the pyridine nucleotide pool. The energetics of the complex and its biochemistry,
as well as its evolution and cellular function in different microbes, is discussed. 相似文献
77.
Inflammasomes: current understanding and open questions 总被引:2,自引:2,他引:0
Bauernfeind F Ablasser A Bartok E Kim S Schmid-Burgk J Cavlar T Hornung V 《Cellular and molecular life sciences : CMLS》2011,68(5):765-783
The innate immune system relies on its capability to detect invading microbes, tissue damage, or stress via evolutionarily
conserved receptors. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family of pattern recognition receptors
includes several proteins that drive inflammation in response to a wide variety of molecular patterns. In particular, the
NLRs that participate in the formation of a molecular scaffold termed the “inflammasome” have been intensively studied in
past years. Inflammasome activation by multiple types of tissue damage or by pathogen-associated signatures results in the
autocatalytic cleavage of caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines,
most importantly interleukin (IL)-1β and IL-18. Here, we review the current knowledge of mechanisms leading to the activation
of inflammasomes. In particular, we focus on the controversial molecular mechanisms that regulate NLRP3 signaling and highlight
recent advancements in DNA sensing by the inflammasome receptor AIM2. 相似文献
78.
Amiot L Ferrone S Grosse-Wilde H Seliger B 《Cellular and molecular life sciences : CMLS》2011,68(3):417-431
Although the expression of the non-classical HLA class I molecule HLA-G was first reported to be restricted to the fetal–maternal
interface on the extravillous cytotrophoblasts, the distribution of HLA-G in normal tissues appears broader than originally
described. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic
lineage. More interestingly, under pathophysiological conditions HLA-G antigens may be expressed on various types of malignant
cells suggesting that HLA-G antigen expression is one strategy used by tumor cells to escape immune surveillance. In this
article, we will focus on HLA-G expression in cancers of distinct histology and its association with the clinical course of
diseases, on the underlying molecular mechanisms of impaired HLA-G expression, on the immune tolerant function of HLA-G in
tumors, and on the use of membrane-bound and soluble HLA-G as a diagnostic or prognostic biomarker to identify tumors and
to monitor disease stage, as well as on the use of HLA-G as a novel therapeutic target in cancer. 相似文献
79.
80.