β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development

Abstract β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development. Further analysis identified E-cadherin as the top positive correlated gene, while hepatocyte growth factor-regulated tyrosine kinase substrate as the top negative correlated gene. Expression of two proteoglycans were also positively correlated with that of β-defensin 1. We have also identified small molecules as potential therapeutic agents to reverse β-defensin 1-associated gene signature. Furthermore, the downregulation of β-defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate, were further confirmed in liver cancer and adjacent normal tissue collected from in-house Chinese liver cancer patients. Together, our results suggest β-defensin 1 plays an important role in protecting HCV progression and liver cancer development

GEMINI 3D spectroscopy of BAL+IR+Fe II QSOs: II. IRAS 04505-2958 an explosive QSO with hypershell and a new scenario for galaxy formation and galaxy end

From a study of BAL + IR + Fe II QSOs (using deep Gemini GMOS-IFU spectroscopy) new results are presented: for IRAS 04505-2958. Specifically, we have studied in detail the out flow (OF) process and their associated structures, mainly at two large galactic scales: (i) two blobs/shells (S1, S2) at radius r = 1.1 and 2.2 kpc; and (ii) an external hypergiant shell (S3) at r = 11 kpc. In addition, the presence of two very extended hypergiant shells (S4, S5) at r = 80 kpc is discussed. From this GMOS study the following main results were obtained: (i) For the external hypergiant shell S3 the kinematics GMOS maps of the ionized gas show very similar features to those observed for the prototype of exploding external supergiant shell: in NGC 5514. (ii) The main knots K1, K2 and K3 -of this hypergiant shell S3- show a stellar population and emission line ratios associated with the presence of a starburst + OF/shocks. (iii) The internal shells S1 and S2 show structures, OF components and properties very similar to those detected in the nuclear shells of Mrk 231. (iv) The shells S1+S2 and S3 are aligned at PA = 131: i.e. suggesting that the OF process is in the blow-out phase with bipolar structure. In addition, the shells S4 and S5 (at 80-100 kpc scale) are aligned at PA = 40, i.e.: a bipolar OF perpendicular to the internal OF. Finally, the generation of UHE cosmic rays and neutrino/ dark-matter -associated with HyNe in BAL + IR + Fe II QSOs- is discussed.Comment: Submitted MNRAS, 81 pages, 25 Figure

A taxonomic backbone for the global synthesis of species diversity in the angiosperm order Caryophyllales

The Caryophyllales constitute a major lineage of flowering plants with approximately 12500 species in 39 families. A taxonomic backbone at the genus level is provided that reflects the current state of knowledge and accepts 749 genera for the order. A detailed review of the literature of the past two decades shows that enormous progress has been made in understanding overall phylogenetic relationships in Caryophyllales. The process of re-circumscribing families in order to be monophyletic appears to be largely complete and has led to the recognition of eight new families (Anacampserotaceae, Kewaceae, Limeaceae, Lophiocarpaceae, Macarthuriaceae, Microteaceae, Montiaceae and Talinaceae), while the phylogenetic evaluation of generic concepts is still well underway. As a result of this, the number of genera has increased by more than ten percent in comparison to the last complete treatments in the Families and genera of vascular plants” series. A checklist with all currently accepted genus names in Caryophyllales, as well as nomenclatural references, type names and synonymy is presented. Notes indicate how extensively the respective genera have been studied in a phylogenetic context. The most diverse families at the generic level are Cactaceae and Aizoaceae, but 28 families comprise only one to six genera. This synopsis represents a first step towards the aim of creating a global synthesis of the species diversity in the angiosperm order Caryophyllales integrating the work of numerous specialists around the world

Chemocentric Informatics Approach to Drug Discovery: Identification and Experimental Validation of Selective Estrogen Receptor Modulators as Ligands of 5-Hydroxytryptamine-6 Receptors and as Potential Cognition Enhancers

We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure- Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5HT6R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT6R actives. Second, we queried chemogenomics data from the Connectivity Map (http://www.broad.mit.edu/cmap/) with the gene expression profile signatures of Alzheimer’s disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT6R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT6R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations