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32.
Davidson AJ Ernst P Wang Y Dekens MP Kingsley PD Palis J Korsmeyer SJ Daley GQ Zon LI 《Nature》2003,425(6955):300-306
Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis. Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis. 相似文献
33.
Stolk L Perry JR Chasman DI He C Mangino M Sulem P Barbalic M Broer L Byrne EM Ernst F Esko T Franceschini N Gudbjartsson DF Hottenga JJ Kraft P McArdle PF Porcu E Shin SY Smith AV van Wingerden S Zhai G Zhuang WV Albrecht E Alizadeh BZ Aspelund T Bandinelli S Lauc LB Beckmann JS Boban M Boerwinkle E Broekmans FJ Burri A Campbell H Chanock SJ Chen C Cornelis MC Corre T Coviello AD d'Adamo P Davies G de Faire U de Geus EJ Deary IJ Dedoussis GV Deloukas P Ebrahim S Eiriksdottir G Emilsson V 《Nature genetics》2012,44(3):260-268
To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause. 相似文献
34.
Malgrange B Borgs L Grobarczyk B Purnelle A Ernst P Moonen G Nguyen L 《Cellular and molecular life sciences : CMLS》2011,68(4):635-649
Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew
indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent
cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed
neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available
methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition,
we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative
diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression
of these neurological disorders. 相似文献
35.
Zusammenfassung Es wird die Relation von Struktur und Wirkung zwischen Dopamin und Apomorphin beim Zwangsnagen der Ratte, nach stereotaktischer Implantation der beiden Substanzen besprochen. 相似文献
36.
37.
Ernst J Kheradpour P Mikkelsen TS Shoresh N Ward LD Epstein CB Zhang X Wang L Issner R Coyne M Ku M Durham T Kellis M Bernstein BE 《Nature》2011,473(7345):43-49
Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease. 相似文献
38.
The identification of chemokines in blood platelets has strengthened our view of these cells as participants in immune host
defense. Platelet chemokines representing prestored and rapidly releasable proteins may play a major role as first-line inflammatory
mediators. This is evident from their capability to recruit early inflammatory cells such as neutrophil granulocytes and monocytes
and even to exhibit direct antimicrobial activity. However, insight is growing that platelet chemokines may be also long-term
regulators, e.g., by activating T lymphocytes, by modulating the formation of endothelium and even thrombocytopoiesis itself.
This review deals with the individual and cooperative functionality of platelet chemokines, as well as their potential as
a basis for therapeutic intervention in the pathology of inflammation, infection, allergy and tumors. Within this context,
therapeutic strategies based on the use of antibodies, modified chemokines, chemokine-binding proteins and chemokine receptor
antagonists as well as first clinical studies will be addressed. 相似文献
39.
Kudernac T Ruangsupapichat N Parschau M Maciá B Katsonis N Harutyunyan SR Ernst KH Feringa BL 《Nature》2011,479(7372):208-211
Propelling single molecules in a controlled manner along an unmodified surface remains extremely challenging because it requires molecules that can use light, chemical or electrical energy to modulate their interaction with the surface in a way that generates motion. Nature's motor proteins have mastered the art of converting conformational changes into directed motion, and have inspired the design of artificial systems such as DNA walkers and light- and redox-driven molecular motors. But although controlled movement of single molecules along a surface has been reported, the molecules in these examples act as passive elements that either diffuse along a preferential direction with equal probability for forward and backward movement or are dragged by an STM tip. Here we present a molecule with four functional units--our previously reported rotary motors--that undergo continuous and defined conformational changes upon sequential electronic and vibrational excitation. Scanning tunnelling microscopy confirms that activation of the conformational changes of the rotors through inelastic electron tunnelling propels the molecule unidirectionally across a Cu(111) surface. The system can be adapted to follow either linear or random surface trajectories or to remain stationary, by tuning the chirality of the individual motor units. Our design provides a starting point for the exploration of more sophisticated molecular mechanical systems with directionally controlled motion. 相似文献
40.
Xiaosong Yang Zhenmin Jin Huenges Ernst Frank R. Schilling Wunder Bernd 《科学通报(英文版)》2001,46(10):867-872
Here we present the results of dehydration melting, melt morphology and fluid migration based on the dehydration melting experiments on natural biotite-plagioclase gneiss performed at the pressure of 1.0—1.4 GPa, and at the temperature of 770—1028℃. Experimental results demonstrate that: (ⅰ) most of melt tends to be distributed along mineral boundaries forming “melt film” even the amount of melt is less than 5 vol%; melt connectivity is controlled not only by melt topology but also by melt fraction; (ⅱ) dehydration melting involves a series of subprocesses including subsolidus dehydration reaction, fluid migration, vapor-present melting and vapor-absent melting; (ⅲ) experiments produce peraluminous granitic melt whose composition is similar to that of High Himalayan leucogranites (HHLG) and the residual phase assemblage is Pl+Qz+ Gat+Bio+Opx± Cpx+Ilm/Rut± Kfs and can be comparable with granulites observed in Himalayas. The experiments provide the evidence that biotite-plagioclase gneiss is one of source rocks of HHLG and dehydration melting is an important way to form HHLG and the granulites. Additionally, experimental results provide constraints on determining the P-T conditions of Himalayan crustal anatexis. 相似文献