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1.
M F Lu  C Pressman  R Dyer  R L Johnson  J F Martin 《Nature》1999,401(6750):276-278
Rieger syndrome, an autosomal dominant disorder, includes ocular, craniofacial and umbilical abnormalities. The pitx2 homeobox gene, which is mutated in Rieger syndrome, has been proposed to be the effector molecule interpreting left-right axial information from the early embryonic trunk to each organ. Here we have used gene targeting in mice to generate a loss-of-function allele that would be predicted to result in organ randomization or isomerization. Although pitx2-/- embryos had abnormal cardiac morphogenesis, mutant hearts looped in the normal direction. Pitx2-/- embryos had correctly oriented, but arrested, embryonic rotation and right pulmonary isomerism. They also had defective development of the mandibular and maxillary facial prominences, regression of the stomodeum and arrested tooth development. Fgf8 expression was absent, and Bmp4 expression was expanded in the branchial-arch ectoderm. These data reveal a critical role for pitx2 in left-right asymmetry but indicate that pitx2 may function at an intermediate step in cardiac morphogenesis and embryonic rotation.  相似文献   

2.
The establishment of the main body axis and the determination of left-right asymmetry are fundamental aspects of vertebrate embryonic development. A link between these processes has been revealed by the frequent finding of midline defects in humans with left-right anomalies. This association is also seen in a number of mutations in mouse and zebrafish, and in experimentally manipulated Xenopus embryos. However, the severity of laterality defects accompanying abnormal midline development varies, and the molecular basis for this variation is unknown. Here we show that mouse embryos lacking the early-response gene SIL have axial midline defects, a block in midline Sonic hedgehog (Shh) signalling and randomized cardiac looping. Comparison with Shh mutant embryos, which have axial defects but normal cardiac looping, indicates that the consequences of abnormal midline development for left-right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2.  相似文献   

3.
Polarized epithelia are fundamental to multicellular life. In animal epithelia, conserved junctional complexes establish membrane diffusion barriers, cellular adherence and sealing of the extracellular space. Plant cellular barriers are of independent evolutionary origin. The root endodermis strongly resembles a polarized epithelium and functions in nutrient uptake and stress resistance. Its defining features are the Casparian strips, belts of specialized cell wall material that generate an extracellular diffusion barrier. The mechanisms localizing Casparian strips are unknown. Here we identify and characterize a family of transmembrane proteins of previously unknown function. These 'CASPs' (Casparian strip membrane domain proteins) specifically mark a membrane domain that predicts the formation of Casparian strips. CASP1 displays numerous features required for a constituent of a plant junctional complex: it forms complexes with other CASPs; it becomes immobile upon localization; and it sediments like a large polymer. CASP double mutants display disorganized Casparian strips, demonstrating a role for CASPs in structuring and localizing this cell wall modification. To our knowledge, CASPs are the first molecular factors that are shown to establish a plasma membrane and extracellular diffusion barrier in plants, and represent a novel way of epithelial barrier formation in eukaryotes.  相似文献   

4.
RIP3 mediates the embryonic lethality of caspase-8-deficient mice   总被引:4,自引:0,他引:4  
Apoptosis and necroptosis are complementary pathways controlled by common signalling adaptors, kinases and proteases; among these, caspase-8 (Casp8) is critical for death receptor-induced apoptosis. This caspase has also been implicated in non-apoptotic pathways that regulate Fas-associated via death domain (FADD)-dependent signalling and other less defined biological processes as diverse as innate immune signalling and myeloid or lymphoid differentiation patterns. Casp8 suppresses RIP3-RIP1 (also known as RIPK3-RIPK1) kinase complex-dependent necroptosis that follows death receptor activation as well as a RIP3-dependent, RIP1-independent necrotic pathway that has emerged as a host defence mechanism against murine cytomegalovirus. Disruption of Casp8 expression leads to embryonic lethality in mice between embryonic days 10.5 and 11.5 (ref. 7). Thus, Casp8 may naturally hold alternative RIP3-dependent death pathways in check in addition to promoting apoptosis. We find that RIP3 is responsible for the mid-gestational death of Casp8-deficient embryos. Remarkably, Casp8(-/-)Rip3(-/-) double mutant mice are viable and mature into fertile adults with a full immune complement of myeloid and lymphoid cell types. These mice seem immunocompetent but develop lymphadenopathy by four months of age marked by accumulation of abnormal T cells in the periphery, a phenotype reminiscent of mice with Fas-deficiency (lpr/lpr; also known as Fas). Thus, Casp8 contributes to homeostatic control in the adult immune system; however, RIP3 and Casp8 are together completely dispensable for mammalian development.  相似文献   

5.
以高蛋白大豆品种"黑农35"和"黑生101"为供试品材料,采用在分化及伸长培养基中分别添加0.2 mg/L 6-BA和0.2 mg/L IBA浓度激素配比,建立了胚尖再生体系,并分别在芽诱导、不定芽伸长和生根3个环节对两种大豆品种进行了比较.结果显示:"黑农35"大豆芽诱导率高于"黑生101"大豆22.15%,两者在已出芽外植体上的平均出芽数比较接近;"黑农35"大豆不定芽伸长速度大于"黑生101"大豆,同时"黑农35"大豆大于1 cm的芽个数也多于"黑生101"大豆;"黑生101"大豆生根率以及根系生长状态好于"黑农35"大豆.本研究为今后以"黑农35"和"黑生101"大豆为材料进行遗传转化研究奠定了基础.  相似文献   

6.
H J Yost 《Nature》1992,357(6374):158-161
The vertebrate body is organized along three geometric axes: anterior-posterior, dorsal-ventral and left-right. Left-right axis formation, displayed in heart and gut development, is the least understood, even though it has been studied for many years. In Xenopus laevis gastrulae, a fibronectin-rich extracellular matrix is deposited on the basal surface of ectoderm cells over which cardiac and visceral primordia move during development. Here I report experiments in which localized perturbation of a small patch of extracellular matrix by microsurgery was correlated with localized randomization of left-right asymmetries. Global perturbation of the extracellular matrix by microinjection of Arg-Gly-Asp peptides or heparinase into the blastocoel resulted in global randomization of left-right asymmetries. From these observations, I suggest that left-right axial information is contained in the extracellular matrix early in development and is independently transmitted to cardiac and visceral primordia.  相似文献   

7.
The asymmetry of rainfall process   总被引:2,自引:0,他引:2  
Using hourly station rain gauge data in the warm season (May-October) during 1961-2006, the climatological features of the evolution of the rainfall process are analyzed by compositing rainfall events centered on the maximum hourly rainfall amount of each event. The results reveal that the rainfall process is asymmetric, which means rainfall events usually reach the maximum in a short period and then experience a relatively longer retreat to the end of the event. The effects of rainfall intensity, duration and peak time, as well as topography, are also considered. It is found that the asymmetry is more obvious in rainfall events with strong intensity and over areas with complex terrain, such as the eastern margin of the Tibetan Plateau, the Hengduan Mountains, and the Yungui Plateau. The asymmetry in short-duration rainfall is more obvious than that in long-duration rainfall, but the regional differences are weaker. The rainfall events that reach the maximum during 14:00-02:00 LST exhibit the strongest asymmetry and those during 08:00-14:00 LST show the weakest asymmetry. The rainfall intensity at the peak time stands out, which means that the rainfall intensity increases and decreases quickly both before and after the peak. These results can improve understanding of the rainfall process and provide metrics for the evaluation of climate models. Moreover, the strong asymmetry of the rainfall process should be highly noted when taking measures to defending against geological hazards, such as collapses, landslides and debris flows throughout southwestern China.  相似文献   

8.
PAS domain of the deduced Org35 protein mediates the interaction with NifA   总被引:3,自引:0,他引:3  
PAS domains are sensory input domains and pro- tein-protein interaction sites that have been identified recently in a family of sensory proteins from all king-doms of life[1,2]. A variety of environmental stimuli such as light, oxygen, redox potential, an…  相似文献   

9.
Friedman M 《Nature》2008,454(7201):209-212
All adult flatfishes (Pleuronectiformes), including the gastronomically familiar plaice, sole, turbot and halibut, have highly asymmetrical skulls, with both eyes placed on one side of the head. This arrangement, one of the most extraordinary anatomical specializations among vertebrates, arises through migration of one eye during late larval development. Although the transformation of symmetrical larvae into asymmetrical juveniles is well documented, the evolutionary origins of flatfish asymmetry are uncertain because there are no transitional forms linking flatfishes with their symmetrical relatives. The supposed inviability of such intermediates gave pleuronectiforms a prominent role in evolutionary debates, leading to attacks on natural selection and arguments for saltatory change. Here I show that Amphistium and the new genus Heteronectes, both extinct spiny-finned fishes from the Eocene epoch of Europe, are the most primitive pleuronectiforms known. The orbital region of the skull in both taxa is strongly asymmetrical, as in living flatfishes, but these genera retain many primitive characters unknown in extant forms. Most remarkably, orbital migration was incomplete in Amphistium and Heteronectes, with eyes remaining on opposite sides of the head in post-metamorphic individuals. This condition is intermediate between that in living pleuronectiforms and the arrangement found in other fishes. Amphistium and Heteronectes indicate that the evolution of the profound cranial asymmetry of extant flatfishes was gradual in nature.  相似文献   

10.
校园网建设初探   总被引:1,自引:0,他引:1  
简述了校园网络建设中网络结构与局域网技术的运用 ,windows95 /98对等网和服务器的设置 ,网络接入 Internet等一些关键技术 .  相似文献   

11.
Ye Y  Shibata Y  Yun C  Ron D  Rapoport TA 《Nature》2004,429(6994):841-847
Elimination of misfolded proteins from the endoplasmic reticulum (ER) by retro-translocation is an important physiological adaptation to ER stress. This process requires recognition of a substrate in the ER lumen and its subsequent movement through the membrane by the cytosolic p97 ATPase. Here we identify a p97-interacting membrane protein complex in the mammalian ER that links these two events. The central component of the complex, Derlin-1, is a homologue of Der1, a yeast protein whose inactivation prevents the elimination of misfolded luminal ER proteins. Derlin-1 associates with different substrates as they move through the membrane, and inactivation of Derlin-1 in C. elegans causes ER stress. Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor.  相似文献   

12.
The Microprocessor complex mediates the genesis of microRNAs   总被引:5,自引:0,他引:5  
  相似文献   

13.
The bcl-2 gene encodes a novel G protein   总被引:5,自引:0,他引:5  
S Haldar  C Beatty  Y Tsujimoto  C M Croce 《Nature》1989,342(6246):195-198
Little is known about the biochemical or functional nature of the proteins encoded by the bcl-2 gene, which undergoes chromosomal translocation in approximately 85% of follicular lymphoma, 20% of diffuse large cell lymphoma and 10% of chronic lymphocytic leukaemia of B cells. Translocation of bcl-2 sequences from chromosome 18 to the JH segment of the immunoglobulin gene at chromosome band 14q32 in B cells results in deregulated expression of this gene, causing high steady state levels of bcl-2 messenger RNA2. DNA sequence data indicate that bcl-2 encodes two proteins by virtue of alternative splicing, designated as Bcl-2 alpha and Bcl-2 beta, with relative molecular masses of 26,000 and 22,000 respectively. Cell fractionation experiments indicate that the bcl-2 alpha gene product is located at the inner surface of the cell membrane, suggesting a possible role in mitogenic signal transduction. We report here that Bcl-2 alpha has GTP-binding activity and a protein sequence that suggests it belongs to the small molecular weight GTP-binding protein (G protein) family.  相似文献   

14.
15.
A Zachowski  J P Henry  P F Devaux 《Nature》1989,340(6228):75-76
The Ca2+-dependent binding of annexin proteins to secretory granule membranes seems to be involved in the early stage of exocytosis. Binding studies have shown that these proteins have a specificity for phosphatidylserine (PtdS) interfaces. Furthermore, aminolipids are necessary for contact and fusion between lipid vesicles or between liposomes and chromaffin granules. Thus, PtdS must be present on the granule outer (cytoplasmic) monolayer. We report here that chromaffin granules possess a mechanism to maintain PtdS orientation, comparable to the ATP-dependent aminophospholipid translocase from human erythrocytes. The translocase, in granules, selectively transports PtdS from the luminal to the cytoplasmic monolayer, provided the incubation medium contains ATP. As this protein shares several properties with the granule vanadate-sensitive ATPase II, we infer that this ATPase, of relative molecular mass 115,000, is the protein responsible for aminophospholipid translocation. This is the first evidence for an ATP-dependent specific phospholipid 'flippase' in intracellular organelles.  相似文献   

16.
In most species the length of a pregnancy exceeds that of the luteal phase of the ovarian cycle. The conceptus within the uterus, therefore, is believed to produce a substance or substances which directly or indirectly prolong the lifespan of the corpus luteum and prevent a return to ovarian cyclicity. This phenomenon is known as maternal recognition of pregnancy. The active substance implicated in signalling maternal recognition of pregnancy in the sheep is an embryonic secretory protein, known as ovine trophoblast protein-1 (oTP-1) (refs 2-4), which is targeted in a paracrine manner to the uterine epithelium of the mother. We report here the primary amino-acid sequence of oTP-1 as inferred from a cloned complementary DNA and demonstrate that the protein is most probably an interferon-alpha.  相似文献   

17.
18.
利益均衡机制与和谐社会的构建   总被引:3,自引:0,他引:3  
和谐社会是社会结构和利益格局比较合理,能够不断有效协调各方面的利益关系,保证社会基本公平和正义。使人们普遍分享改革和发展带来的收益。构建和谐社会问题的关键是如何形成在市场经济条件下的利益均衡机制。  相似文献   

19.
The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion.   总被引:7,自引:0,他引:7  
I Stamenkovic  B Seed 《Nature》1990,345(6270):74-77
Interaction with antigen-presenting accessory cells is thought to be an important step in B-cell activation, and the B-cell receptor CD22, which is coordinately expressed with surface immunoglobulin, has been proposed to participate in the antigen response. Here we show that CD22 has a structure closely related to myelin-associated glycoprotein (MAG, a neuronal adhesion protein), and mediates monocyte and erythrocyte adhesion. Like CD2, the T-cell erythrocyte receptor, CD22 may facilitate antigen recognition by promoting antigen-nonspecific contacts with accessory cells.  相似文献   

20.
盾叶薯蓣高频再生体系的建立   总被引:1,自引:0,他引:1  
以盾叶薯蓣(Dioscorea zingiberensis C. H. Wright)无菌苗的茎段和叶片为外植体,研究了适于盾叶薯蓣再生的外植体类型和植物生长调节剂组合,建立了一个高频的离体再生体系.结果表明:以无菌苗茎段为外植体,在2.0~3.0 mg·L-1 6-苄氨基腺嘌呤(BA)作用下可诱导产生致密的胚性愈伤组织;转移到含2.0~3.0 mg·L-1 BA和0.2~0.5 mg·L-1 α-萘乙酸(NAA)的分化培养基上可迅速分化出大量的丛生芽,分化率达90%以上;无根苗在1/2 MS+NAA 0.1~0.2 mg·L-1的生根培养基上生根率超过90%,移栽成活率达70%以上.  相似文献   

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