Phagocyte-derived catecholamines enhance acute inflammatory injury

It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of alpha2-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an alpha2-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response.     

Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster

Human adenocarcinomas commonly harbor mutations in the KRAS and MYC proto-oncogenes and the TP53 tumor suppressor gene. All three genetic lesions are potentially pro-angiogenic, as they sustain production of vascular endothelial growth factor (VEGF). Yet Kras-transformed mouse colonocytes lacking p53 formed indolent, poorly vascularized tumors, whereas additional transduction with a Myc-encoding retrovirus promoted vigorous vascularization and growth. In addition, VEGF levels were unaffected by Myc, but enhanced neovascularization correlated with downregulation of anti-angiogenic thrombospondin-1 (Tsp1) and related proteins, such as connective tissue growth factor (CTGF). Both Tsp1 and CTGF are predicted targets for repression by the miR-17-92 microRNA cluster, which was upregulated in colonocytes coexpressing K-Ras and c-Myc. Indeed, miR-17-92 knockdown with antisense 2'-O-methyl oligoribonucleotides partly restored Tsp1 and CTGF expression; in addition, transduction of Ras-only cells with a miR-17-92-encoding retrovirus reduced Tsp1 and CTGF levels. Notably, miR-17-92-transduced cells formed larger, better-perfused tumors. These findings establish a role for microRNAs in non-cell-autonomous Myc-induced tumor phenotypes.     

Proteolytic control of TGF-β co-receptor activity by BMP-1/tolloid-like proteases revealed by quantitative iTRAQ proteomics

The metalloproteinase BMP-1 (bone morphogenetic protein-1) plays a major role in the control of extracellular matrix (ECM) assembly and growth factor activation. Most of the growth factors activated by BMP-1 are members of the TGF-β superfamily known to regulate multiple biological processes including embryonic development, wound healing, inflammation and tumor progression. In this study, we used an iTRAQ (isobaric tags for relative and absolute quantification)-based quantitative proteomic approach to reveal the release of proteolytic fragments from the cell surface or the ECM by BMP-1. Thirty-eight extracellular proteins were found in significantly higher or lower amounts in the conditioned medium of HT1080 cells overexpressing BMP-1 and thus, could be considered as candidate substrates. Strikingly, three of these new candidates (betaglycan, CD109 and neuropilin-1) were TGF-β co-receptors, also acting as antagonists when released from the cell surface, and were chosen for further substrate validation. Betaglycan and CD109 proved to be directly cleaved by BMP-1 and the corresponding cleavage sites were extensively characterized using a new mass spectrometry approach. Furthermore, we could show that the ability of betaglycan and CD109 to interact with TGF-β was altered after cleavage by BMP-1, leading to increased and prolonged SMAD2 phosphorylation in BMP-1-overexpressing cells. Betaglycan processing was also observed in primary corneal keratocytes, indicating a general and novel mechanism by which BMP-1 directly affects signaling by controlling TGF-β co-receptor activity. The proteomic data have been submitted to ProteomeXchange with the identifier PXD000786 and doi: 10.6019/PXD000786.     

Insect-mediated pollination in slickspot peppergrass, Lepidium papilliferum L. (Brassicaceae), and its implications for population viability

Field experiments on the pollination biology of slickspot peppergrass, Lepidium papilliferum L. (Brassicaceae), a rare species endemic to microsites in sagebrush-steppe habitat in southwestern Idaho, were conducted at 2 sites from May to July 2001. Site KB contained over 10,000 plants, whereas site WG contained less than 150 plants. Insect exclusion experiments revealed that seed production in L. papilliferum is dependent on insect-mediated pollination; median percent seed set dropped from 70% to 2% when insects were excluded from flowers. A total of 25 insect families from 5 orders visited L. papilliferum flowers: 24 families at KB and 11 families at WG. Only 9 families contained more than trace amounts of pollen on their bodies: Hymenoptera-Anthophoridae, Apidae, Colletidae, Halictidae, Sphecidae, Vespidae; Coleoptera-Cerambycidae, Dermestidae; Diptera-Syrphidae. Insects from these families are likely responsible for pollination of L. papilliferum , although some may be of only minor significance due to their infrequent visits to flowers. Two of the 4 most common and pollen-laden insects found at KB, honey bees ( Apis mellifera ) and colletid bees, were absent or rare at WG. Three other pollen-carrying families present at KB, Sphecidae, Vespidae, and Halictidae, were not found at WG. We raise several possible explanations for this disparity in pollinator communities between sites and discuss the importance of pollinator diversity to the long term viability of L. papilliferum .     

植酸酶分泌型酵母工程菌的构建

通过逆转录PCR从无花果曲霉总RNA中扩增出1.4-kb带信号肽的植酸酶基因，将其克隆到穿梭表示载体pYES2，构建了含有目的的基因的重组质粒pYPA1.用pYPA1转化酿酒酵母INVSc1菌株，成功地构建了能分泌活性植酸酶的工程菌株。该菌株的成功构建为饲料和食品添加剂以及解磷工程菌肥的开发奠定了基础。     

An Optimal Algorithm To Recognize Robinsonian Dissimilarities

A dissimilarity D on a finite set S is said to be Robinsonian if S can be totally ordered in such a way that, for every i < j < k, D (i, j) ≤ D (i, k) and D (j, k) ≤ D (i, k). Intuitively, D is Robinsonian if S can be represented by points on a line. Recognizing Robinsonian dissimilarities has many applications in seriation and classification. In this paper, we present an optimal O (n ²) algorithm to recognize Robinsonian dissimilarities, where n is the cardinal of S. Our result improves the already known algorithms.     

Characterization of Fe-S minerals influenced by buried ancient woods in the intertidal zone, East China Sea

An ancient wood layer dated at about 5600 cal. a BP by AMS14C dating was discovered in the intertidal zone, East China Sea. Samples affected by ancient woods, including fresh coast bedrock, weathering bedrock, seepage water from coast, seepage water from ancient wood layer, intertidal seawater, fresh water, beach mud, ancient wood barks and ancient peat, were collected for geochemical analysis. The beach mud and the bacteriogenic iron oxides （BIOS） in coastal seepage water were analyzed by min- eralogical and high-resolution transmission electron microscopy （HRTEM）-selected area electron dif- fraction （SAED） analysis. Inorganic sulfur compositions and b＇34S of the ancient peat and the beach mud were determined. The results showed that Fe, Mn, S （SO~-） were enriched in the intertidal area at different levels, very likely caused by fermentation of ancient woods. The presence of abundant iron- oxidizing bacteria （FeOB） and sulfate-reducing bacteria （SRB） in this intertidal zone was confirmed by HRTEM-SAED observation, and these bacteria were involved in Fe-S cycle to induce extracellular biomineralization. The negative ~4Sv.cDT （--2.9%o） likely indicated the biogenic origin of iron-sulfide minerals in the beach mud at high sulfate reduction rate （SRR）. These findings are helpful for under- standing the biogeochemical Fe-S cycle and biomineralization process at high organic matter deposition rate and high SRR in the intertidal zone, estuary, or near shoreline.