Soluble polysialylated NCAM: a novel player of the innate immune system in the lung

Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing “neutrophil extracellular traps”, which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes.     

选择实验的理论和应用——以中国退耕还林为例

选择实验的理论基础来自于要素价值理论和随机效用理论,既是一种对环境资源进行价值评估的重要方法,也是揭示研究对象政策偏好的重要手段。利用该方法不仅可以通过对支付意愿或接受赔偿意愿进行评估,进而对一项政策的各个要素的相对重要性进行排序,还可以得到因多个政策要素同时改变时导致的价值变化,从而有助于政策制订者对政策进行调整。本文在评述选择实验的基本理论和方法的基础上,以中国正在实施的退耕还林工程为例,利用选择实验方法对该政策进行了评估,并且基于研究结果对未来的政策改进提出了相关建议。     

HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers

DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n?=?19), diploid (n?=?31), and aneuploid (n?=?47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.     

Biogenesis of bacterial inner-membrane proteins

All cells must traffic proteins into and across their membranes. In bacteria, several pathways have evolved to enable protein transfer across the inner membrane, the periplasm, and the outer membrane. The major route of protein translocation in and across the cytoplasmic membrane is the general secretion pathway (Sec-pathway). The biogenesis of membrane proteins not only requires protein translocation but also coordinated targeting to the membrane beforehand and folding and assembly into their protein complexes afterwards to function properly in the cell. All these processes are responsible for the biogenesis of membrane proteins that mediate essential functions of the cell such as selective transport, energy conversion, cell division, extracellular signal sensing, and motility. This review will highlight the most recent developments on the structure and function of bacterial membrane proteins, focusing on the journey that integral membrane proteins take to find their final destination in the inner membrane.     

Organocatalytic Domino-methylenation/Diels-Alder Reactions

1 Results Organocatalytic reactions are currently very much en vogue as the term implies a connotation of ecologically benign chemistry.In addition,beautiful new results have been achieved over the last few years which triggered a dramatic increase in publications[1].Related to this topic is the catalysis of organic transformations by hydrogen bond donors and organic Brnsted acids[2].From an industrial point of view,these reactions can be beneficial when performed in water in high concentration,prerequ...     

Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency

Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage. Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis.     

The far-ultraviolet signature of the 'missing' baryons in the Local Group of galaxies

The number of baryons detected in the low-redshift (z < 1) Universe is far smaller than the number detected in corresponding volumes at higher redshifts. Simulations of the formation of structure in the Universe show that up to two-thirds of the 'missing' baryons may have escaped detection because of their high temperature and low density. One of the few ways to detect this matter directly is to look for its signature in the form of ultraviolet absorption lines in the spectra of background sources such as quasars. Here we show that the amplitude of the average velocity vector of 'high velocity' O vi (O5+) absorption clouds detected in a survey of ultraviolet emission from active galactic nuclei decreases significantly when the vector is transformed to the frames of the Galactic Standard of Rest and the Local Group of galaxies. At least 82 per cent of these absorbers are not associated with any 'high velocity' atomic hydrogen complex in our Galaxy, and are therefore likely to result from a primordial warm-hot intergalactic medium pervading an extended corona around the Milky Way or the Local Group. The total mass of baryons in this medium is estimated to be up to approximately 10(12) solar masses, which is of the order of the mass required to dynamically stabilize the Local Group.