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121.
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.  相似文献   
122.
The evolutionarily conserved SLX4 protein, a key regulator of nucleases, is critical for DNA damage response. SLX4 nuclease complexes mediate repair during replication and can also resolve Holliday junctions formed during homologous recombination. Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia. Btbd12-deficient animals are born at sub-Mendelian ratios, have greatly reduced fertility, are developmentally compromised and are prone to blood cytopenias. Btbd12(-/-) cells prematurely senesce, spontaneously accumulate damaged chromosomes and are particularly sensitive to DNA crosslinking agents. Genetic complementation reveals a crucial requirement for Btbd12 (also known as Slx4) to interact with the structure-specific endonuclease Xpf-Ercc1 to promote crosslink repair. The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway.  相似文献   
123.
124.
1 Results The enantioselective addition of allylic organometallic reagents to aldehydes is a fundamental tool in organic synthesis.The high degree of both diastereo-and enantioselectivity gives the possibility to obtain a wide series of homoallylic alcohols,versatile intermediates in a great number of synthesis[1]. One of the most successful approaches is related to the discovery that organocatalytic activation of the nucleophilic allyltrichlorosilanes by means of neutral Lewis bases,such as formamides,...  相似文献   
125.
In coal mines in such countries as China and Russia,most of the coal mine methane(CMM) generated during mining is emitted to the atmosphere without any effective usage,because the methane concentration of CMM is relatively low and not allowed to be used as fuel for safety reasons.Methane is one of the greenhouse gases.Therefore,if it becomes possible to concentrate CMM to an acceptable level for use as fuel,this will greatly contribute to reduction of greenhouse gas emissions.With the aim of gaining approva...  相似文献   
126.
B Sur  R B Rogge  R P Hammond  V N Anghel  J Katsaras 《Nature》2001,414(6863):525-527
The idea of atomic-resolution holography has its roots in the X-ray work of Bragg and in Gabor's electron interference microscope. Gabor's lensless microscope was not realized in his time, but over the past twelve years there has been a steady increase in the number of reports on atomic-resolution holography. All of this work involves the use of electrons or hard X-rays to produce the hologram. Neutrons are often unique among scattering probes in their interaction with materials: for example, the relative visibility of hydrogen and its isotopes is a great advantage in the study of polymers and biologically relevant materials. Recent work proposed that atomic-resolution holography could be achieved with thermal neutrons. Here we use monochromatic thermal neutrons, adopting the inside-source concept of Sz?ke, to image planes of oxygen atoms located above and below a single hydrogen atom in the oxide mineral simpsonite.  相似文献   
127.
Maternal control of resting-egg production in Daphnia.   总被引:1,自引:0,他引:1  
V Alekseev  W Lampert 《Nature》2001,414(6866):899-901
Many planktonic organisms produce 'resting' stages when the environmental conditions deteriorate. Like seeds, resting stages can survive unfavourable conditions. The crustacean Daphnia normally reproduces by means of parthenogenetically produced normal, not resting, eggs-but occasionally switches to bisexual reproduction, which results in two resting eggs encased in a robust structure carried on the back of the female. This 'ephippium' is shed with the next moult, and can survive dormant for many years. The induction of resting-egg production requires multiple environmental stimuli, one of them being photoperiod. The switch from production of parthenogenetic eggs to resting eggs in Daphnia has recently been shown to be influenced by a maternal food effect. Here we present evidence that female Daphnia transmit information not only about food but also on photoperiod to their offspring, and influence the production of resting eggs in the next generation. The combined maternal effects can be relevant for the correct timing of resting-egg production-for example, in discriminating between spring and autumn conditions.  相似文献   
128.
The activation of ubiquitin and related protein modifiers is catalysed by members of the E1 enzyme family that use ATP for the covalent self-attachment of the modifiers to a conserved cysteine. The Escherichia coli proteins MoeB and MoaD are involved in molybdenum cofactor (Moco) biosynthesis, an evolutionarily conserved pathway. The MoeB- and E1-catalysed reactions are mechanistically similar, and despite a lack of sequence similarity, MoaD and ubiquitin display the same fold including a conserved carboxy-terminal Gly-Gly motif. Similar to the E1 enzymes, MoeB activates the C terminus of MoaD to form an acyl-adenylate. Subsequently, a sulphurtransferase converts the MoaD acyl-adenylate to a thiocarboxylate that acts as the sulphur donor during Moco biosynthesis. These findings suggest that ubiquitin and E1 are derived from two ancestral genes closely related to moaD and moeB. Here we present the crystal structures of the MoeB-MoaD complex in its apo, ATP-bound, and MoaD-adenylate forms, and highlight the functional similarities between the MoeB- and E1-substrate complexes. These structures provide a molecular framework for understanding the activation of ubiquitin, Rub, SUMO and the sulphur incorporation step during Moco and thiamine biosynthesis.  相似文献   
129.
Even though every cell in a multicellular organism contains the same genes, the differing spatiotemporal expression of these genes determines the eventual phenotype of a cell. This means that each cell type contains a specific epigenetic program that needs to be replicated through cell divisions, along with the genome, in order to maintain cell identity. The stable inheritance of these programs throughout the cell cycle relies on several epigenetic mechanisms. In this review, DNA methylation and histone methylation by specific histone lysine methyltransferases (KMT) and the Polycomb/Trithorax proteins are considered as the primary mediators of epigenetic inheritance. In addition, non-coding RNAs and nuclear organization are implicated in the stable transfer of epigenetic information. Although most epigenetic modifications are reversible in nature, they can be stably maintained by self-recruitment of modifying protein complexes or maintenance of these complexes or structures through the cell cycle.  相似文献   
130.
Vegetation characteristics of 15 sagebrush community types identified on the Humboldt National Forest, northeastern Nevada, are described. A total of 218 plant species were found over the 372 relatively undisturbed rangeland communities sampled. The dominant plant families encountered were the Asteraceae (45 taxa), Poaceae (32 taxa), Scrophulariaceae (14 taxa), and the Fabaceae (12 taxa). Average annual dry weight production of the community types ranged from about 400 kg/ha/yr on types with Artemisia nova as the dominant sagebrush species to 1,200 kg/ha/yr on some A. tridentata ssp. vaseyana community types. A general increase in species richness and vegetation plus litter ground cover was observed within community types as the dominant sagebrush species changed from A. nova to A. arbuscula to A. longiloba to A. tridentata spp. tridentata to A. tridentata ssp. vaseyana . Major differences in plant species production and constancy exist between the sagebrush community types studied.  相似文献   
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