Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories.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.     

A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity

Despite the sequencing of the human and mouse genomes, few genetic mechanisms for protecting against autoimmune disease are currently known. Here we systematically screen the mouse genome for autoimmune regulators to isolate a mouse strain, sanroque, with severe autoimmune disease resulting from a single recessive defect in a previously unknown mechanism for repressing antibody responses to self. The sanroque mutation acts within mature T cells to cause formation of excessive numbers of follicular helper T cells and germinal centres. The mutation disrupts a repressor of ICOS, an essential co-stimulatory receptor for follicular T cells, and results in excessive production of the cytokine interleukin-21. sanroque mice fail to repress diabetes-causing T cells, and develop high titres of autoantibodies and a pattern of pathology consistent with lupus. The causative mutation is in a gene of previously unknown function, roquin (Rc3h1), which encodes a highly conserved member of the RING-type ubiquitin ligase protein family. The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability.     

污泥龄对活性污泥处理微量磺胺类药物的影响

为了研究污泥龄对活性污泥系统处理微量磺胺类药物（5 μg/L）的影响,共运行了4个试验室规模（3L）的序批式活性污泥反应器（SBR）,其污泥龄分别为2、8、14、20 d。批次摇瓶试验通过设置3个工况（正常运行,加入生物抑制剂,无微生物）来讨论在1个运行周期（8 h）中对浓度惟5 μg/L磺胺甲恶唑的吸附作用、生物降解作用和挥发损失。试验结果显示对磺胺甲恶唑的总去除量为2.14 ± 0.60 μg/g SS,吸附作用占总去除量的63%;磺胺嘧啶为1.14 ± 0.63 μg/g SS,83%;磺胺间二甲氧为2.33± 0.67 μg/g SS, 35%;磺胺甲基嘧啶为2.45 ± 0.85 μg/g SS,55%;磺胺类药物的去除效果与污泥的污泥龄有着非常显著的关系（p<0.02）。通过运行加入磺胺甲恶唑（进水5 μg/L)的反应器60 d,4个反应器对磺胺甲恶唑的平均去除率分别为10%、41%、51%、58%,处理效果随着污泥龄的增加而变好,同时单位污泥去除率随着污泥龄的增加而降低,SRT=2 d的反应器由于存在大量的丝状菌,使得单位污泥对磺胺甲恶唑去除率大大高于其他3个反应器。通过分子生物学分析,发现微生物群落结构的变化不大,从而说明了影响磺胺类药物处理效果的主要因素在于更强的吸附能力,更高的污泥浓度。     

Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP

Endoplasmic reticulum (ER) chaperones and ER stress have been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer and Parkinson diseases, but their contribution to neuron death remains uncertain. In this study, we establish a direct in vivo link between ER dysfunction and neurodegeneration. Mice homozygous with respect to the woozy (wz) mutation develop adult-onset ataxia with cerebellar Purkinje cell loss. Affected cells have intracellular protein accumulations reminiscent of protein inclusions in both the ER and the nucleus. In addition, upregulation of the unfolded protein response, suggestive of ER stress, occurs in mutant Purkinje cells. We report that the wz mutation disrupts the gene Sil1 that encodes an adenine nucleotide exchange factor of BiP, a crucial ER chaperone. These findings provide evidence that perturbation of ER chaperone function in terminally differentiated neurons leads to protein accumulation, ER stress and subsequent neurodegeneration.     

Regulatory changes underlying expression differences within and between Drosophila species

Differences in gene expression are an important source of phenotypic variation, and can be caused by changes in cis and/or trans regulation. cis-regulatory variants alter allele-specific expression, whereas trans-regulatory variants influence expression of both alleles in a diploid cell. Because of this difference, we hypothesize that natural selection may favor one type of change over the other. Here, we investigate contributions of cis- and trans-regulatory changes to variable intra- and interspecific gene expression using four strains of Drosophila melanogaster, three strains of D. simulans and a total of 78 genes. We show that cis-regulatory changes account for a greater proportion of the expression differences observed between rather than within species. These data are inconsistent with a neutral model assuming equal probabilities of fixation for cis- and trans-regulatory polymorphisms, suggesting that natural selection influences the molecular mechanisms underlying divergent gene expression. Specifically, cis-regulatory changes seem to accumulate preferentially over time.     

Mechanochemical preparation and structural characterization of Ta-doped chlorapatite nanopowders

Nanocrystalline tantalum-doped chlorapatite(Ta-doped ClA) was successfully synthesized using a facile mechanochemical method. In the absence of the dopant, milling for 3 h led to the formation of a poorly crystalline hydroxyapatite, while in its presence of the Ta dopant, Ta-doped ClA nanopowders were produced as a result of an oncoming reaction. The results indicated that lattice micro-strain, crystallite size, crystallinity level, phase percentage and hexagonal lattice constants of the substituted apatite nanopowders were dramatically affected by the doping concentration. The a-axis and unit cell volume increased with the increase in the doping concentration, owing to the ionic radius difference of Cl~- and OH~- ions. From the TEM observations, the doped powders consisted of nanoneedles with a mean size of 60 ± 20 nm in length and 14 ±4 nm in width.     

The value of data

Data citation and the derivation of semantic constructs directly from datasets have now both found their place in scientific communication. The social challenge facing us is to maintain the value of traditional narrative publications and their relationship to the datasets they report upon while at the same time developing appropriate metrics for citation of data and data constructs.