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991.
Shojaei F Trowbridge J Gallacher L Yuefei L Goodale D Karanu F Levac K Bhatia M 《Developmental cell》2005,8(5):651-663
The molecular basis governing functional behavior of human hematopoietic stem cells (HSCs) is largely unknown. Here, using in vitro and in vivo assays, we isolate and define progenitors versus repopulating HSCs from multiple stages of human development for global gene expression profiling. Accounting for both the hierarchical relationship between repopulating cells and their progenitors, and the enhanced HSC function unique to early stages of ontogeny, the human homologs of Hairy Enhancer of Split-1 (HES-1) and Hepatocyte Leukemia Factor (HLF) were identified as candidate regulators of HSCs. Transgenic human hematopoietic cells expressing HES-1 or HLF demonstrated enhanced in vivo reconstitution ability that correlated to increased cycling frequency and inhibition of apoptosis, respectively. Our report identifies regulatory factors involved in HSC function that elicit their effect through independent systems, suggesting that a unique orchestration of pathways fundamental to all human cells is capable of controlling stem cell behavior. 相似文献
992.
Signaling through CD5 Activates a Pathway Involving Phosphatidylinositol 3-Kinase, Vav, and Rac1 in Human Mature T Lymphocytes 总被引:4,自引:0,他引:4 下载免费PDF全文
Sonja I. Gringhuis Lou F. M. H. de Leij Paul J. Coffer Edo Vellenga 《Molecular and cellular biology》1998,18(3):1725-1735
CD5 acts as a coreceptor on T lymphocytes and plays an important role in T-cell signaling and T-cell–B-cell interactions. Costimulation of T lymphocytes with anti-CD5 antibodies results in an increase of the intracellular Ca2+ levels, and subsequently in the activation of Ca2+/calmodulin-dependent (CaM) kinase type IV. In the present study, we have characterized the initial signaling pathway induced by anti-CD5 costimulation. The activation of phosphatidylinositol (PI) 3-kinase through tyrosine phosphorylation of its p85 subunit is a proximal event in the CD5-signaling pathway and leads to the activation of the lipid kinase activity of the p110 subunit. The PI 3-kinase inhibitors wortmannin and LY294002 inhibit the CD5-induced response as assessed in interleukin-2 (IL-2) secretion experiments. The expression of an inactivated Rac1 mutant (Rac1 · N17) in T lymphocytes transfected with an IL-2 promoter-driven reporter construct also abrogates the response to CD5 costimulation, while the expression of a constitutively active Rac1 mutant (Rac1-V12) completely replaces the CD5 costimulatory signal. The Rac1-specific guanine nucleotide exchange factor Vav is heavily phosphorylated on tyrosine residues upon CD5 costimulation, which is a prerequisite for its activation. A role for Vav in the CD5-induced signaling pathway is further supported by the findings that the expression of a dominant negative Vav mutant (Vav-C) completely abolishes the response to CD5 costimulation while the expression of a constitutively active Vav mutant [Vav(Δ1–65)] makes the CD5 costimulation signal superfluous. Wortmannin is unable to block the Vav(Δ1–65)- or Rac1 · V12-induced signals, indicating that both Vav and Rac1 function downstream from PI 3-kinase. Vav and Rac1 both act upstream from the CD5-induced activation of CaM kinase IV, since KN-62, an inhibitor of CaM kinases, and a dominant negative CaM kinase IV mutant block the Vav(Δ1–65)-and Rac1 · V12-mediated signals. We propose a model for the CD5-induced signaling pathway in which the PI 3-kinase lipid products, together with tyrosine phosphorylation, activate Vav, resulting in the activation of Rac1 by the Vav-mediated exchange of GDP for GTP. 相似文献
993.
Jianjun Zhao Maria-Jo?o Paulo Diaan Jamar Ping Lou Fred van Eeuwijk Guusje Bonnema Dick Vreugdenhil Maarten Koornneef 《Génome》2007,50(10):963-973
Association mapping was used to investigate the genetic basis of variation within Brassica rapa, which is an important vegetable and oil crop. We analyzed the variation of phytate and phosphate levels in seeds and leaves and additional developmental and morphological traits in a set of diverse B. rapa accessions and tested association of these traits with AFLP markers. The analysis of population structure revealed four subgroups in the population. Trait values differed between these subgroups, thus defining associations between population structure and trait values, even for traits such as phytate and phosphate levels. Marker-trait associations were investigated both with and without taking population structure into account. One hundred and seventy markers were found to be associated with the observed traits without correction for population structure. Association analysis with correction for population structure led to the identification of 27 markers, 6 of which had known map positions; 3 of these were confirmed in additional QTL mapping studies. 相似文献
994.
995.
996.
Xie Luo Xiaolei Su Jingmiao Cui Ya Lou Ru Li Xiumei Luo Yuanqin Zeng Yaobo Xu Jinyan Dong 《Ecological Research》2016,31(3):407-416
Impoundment of the Three Gorges Reservoir (TGR) has dramatically influenced the riparian environment and shaped a new drawdown zone, which has experienced long-term winter conditions and short periods of summer flooding. The community structure and diversity of arbuscular mycorrhizal (AM) fungi (AMF) were investigated in three areas with different fertilization histories [Area A (5 years of fertilization), Area B (3 years of fertilization) and Area C (no fertilization)] in the drawdown zone of the TGR. Altogether, 50 AMF species were identified; the genera Acaulospora, Funneliformis and Glomus were predominant. The AM fungal community differed among areas A, B and C. A higher isolation frequency and relative abundance of Acaulospora, Ambispora, Entrophospora and Paraglomus were observed in areas A and B; however, Claroideoglomus, Diversispora, Sclerocystis and Septoglomus were more abundant in Area C. The highest spore density occurred in Area C, and was slightly lower in Area A and lowest in Area B. Conversely, species richness and diversity indices (Shannon–Wiener and evenness indices) were the highest in Area A, followed by areas C and B. Based on nonmetric multidimensional scaling analyses, the distribution of AMF was influenced by plant host, fertilization practice and environmental factors. Among them, the soil physicochemical properties were the main drivers affecting AMF, in which three edaphic attributes (carbon/nitrogen ratio, available phosphorus and potassium content) were significantly correlated (P < 0.001) with the AM fungal community composition in the three areas of the drawdown zone of the TGR. 相似文献
997.
Jinqi Ren Lin Huo Wenjuan Wang Yong Zhang Wei Li Jizhong Lou Tao Xu Wei Feng 《The Journal of biological chemistry》2016,291(7):3581-3594
Processive kinesin motors often contain a coiled-coil neck that controls the directionality and processivity. However, the neck coil (NC) of kinesin-3 is too short to form a stable coiled-coil dimer. Here, we found that the coiled-coil (CC1)-forkhead-associated (FHA) tandem (that is connected to NC by Pro-390) of kinesin-3 KIF13A assembles as an extended dimer. With the removal of Pro-390, the NC-CC1 tandem of KIF13A unexpectedly forms a continuous coiled-coil dimer that can be well aligned into the CC1-FHA dimer. The reverse introduction of Pro-390 breaks the NC-CC1 coiled-coil dimer but provides the intrinsic flexibility to couple NC with the CC1-FHA tandem. Mutations of either NC, CC1, or the FHA domain all significantly impaired the motor activity. Thus, the three elements within the NC-CC1-FHA tandem of KIF13A are structurally interrelated to form a stable dimer for activating the motor. This work also provides the first direct structural evidence to support the formation of a coiled-coil neck by the short characteristic neck domain of kinesin-3. 相似文献
998.
999.
The transcription factors MS188 and AMS form a complex to activate the expression of CYP703A2 for sporopollenin biosynthesis in Arabidopsis thaliana 下载免费PDF全文
1000.
Jianshu Dong Fahui Li Feng Gao Jia Wei Yajing Lin Yong Zhang Jizhong Lou Guangfeng Liu Yuhui Dong Lin Liu Hongmin Liu Jiangyun Wang Weimin Gong 《Journal of molecular biology》2018,430(21):4183-4194
The accurate modification of the tRNAIle anticodon wobble cytosine 34 is critical for AUA decoding in protein synthesis. Archaeal tRNAIle2 cytosine 34 is modified with agmatine in the presence of ATP by TiaS (tRNAIle2 agmatidine synthetase). However, no structure of apo-form full-length TiaS is available currently. Here, the crystal structures of apo TiaS and a complex of TiaS–agmatine–AMPPCP–Mg are presented, with properly folded zinc ribbon and Cys4-zinc coordination identified. Compared with tRNAIle2-bound form, the architecture of apo TiaS shows a totally different conformation of zinc ribbon. Molecular dynamics simulations of the docking complex between free-state TiaS and tRNAIle2 suggest that zinc ribbon domain is capable of performing large-scale motions to sample substrate binding-competent conformation. Principle component analysis and normal mode analysis show consistent results about the relative directionality of functionally correlated zinc ribbon motions. Apo TiaS and TiaS–agmatine–AMPPCP–Mg/TiaS–AMPCPP–Mg complex structures capture two snapshots of the flexible ATP-Mg binding p2loop step-by-step stabilization. Research from this study provides new insight into TiaS functional mechanism and the dynamic feature of zinc ribbons. 相似文献