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"Martin, George R. R"
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A knight of the seven kingdoms
\"Taking place nearly a century before the events of A Game of Thrones, [this book] compiles the first three official prequel novellas to George R.R. Martin's ongoing masterwork, A Song of Ice and Fire. These never-before-collected [but previously published] adventures recount an age when the Targaryen line still holds the Iron Throne, and the memory of the last dragon has not yet passed from living consciousness\"--Dust jacket flap.
Book
Zika virus-like particle (VLP) based vaccine
The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development.
Journal Article
Aces high
\"After the alien virus struck humanity in the wake of World War II, a handful of the survivors found they possessed superhuman powers. The Wild Cards shared-world volumes tell their story. Here in book two, we trace these heroes and villains through the tumultuous 1980s, in stories from SF and fantasy giants such as George R. R. Martin, Roger Zelazny, Pat Cadigan, Lewis Shiner, Walter Jon Williams, and others\"-- Provided by publisher.
Book
A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice
Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-β1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-β1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis.
Journal Article
Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis
Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients.
Dermal interstitial fluid sample from the involved forearm skin, and synchronous plasma samples were collected from SSc patients (n = 26, diffuse cutaneous SSc (DcSSc) n = 20, limited cutaneous SSc (LcSSc) n = 6), and healthy controls (HC) (n = 10) and profiled by Luminex® array for inflammatory cytokines, chemokines, and growth factors.
Luminex® profiling of the dermal blister fluid showed increased inflammatory cytokines (median interleukin ( IL)-6 in SSc 39.78 pg/ml, HC 5.51 pg/ml, p = 0.01, median IL-15 in SSc 6.27 pg/ml, HC 4.38 pg/ml, p = 0.03), chemokines (monocyte chemotactic protein (MCP)-3 9.81 pg/ml in SSc, 7.18 pg/ml HC, p = 0.04), and profibrotic growth factors (platelet derived growth factor (PDGF)-AA 10.38 pg/ml versus 6.94 pg/ml in HC, p = 0.03). In general dermal fluid and plasma cytokine levels did not correlate, consistent with predominantly local production of these factors within the dermal lesions, rather than leakage from the serum. In hierarchical clustering and network analysis IL-6 emerged as a key central mediator.
Our data confirm that an immuno-inflammatory environment and aberrant vascular repair are intimately linked to fibroblast activation in lesional skin in SSc. This non-invasive method could be used to profile disease activity in the clinic, and identifies key inflammatory or pro-fibrotic proteins that might be targeted therapeutically. Distinct subgroups of SSc may be defined that show innate or adaptive immune cytokine signatures.
Journal Article
Nightflyers
\"When a scientific expedition is launched to study a mysterious alien race, the only ship available is the Nightflyer, a fully autonomous vessel manned by a single human. But Captain Royd Eris remains locked away, interacting with his passengers only as a disembodied voice--or a projected hologram no more substantial than a ghost. Yet thats not the only reason the ship seems haunted. The team's telepath, Thale Lasamer, senses another presence aboard the Nightflyer--something dangerous, volatile, and alien. Captain Eris claims to know nothing about the elusive intruder, and when someone, or something, begins killing off the expeditions members, hes unable--or unwilling--to stem the bloody tide. Only Melantha Jhirl, a genetically enhanced outcast with greater strength, stamina, and intelligence than other humans, has a chance of solving the mystery--and stopping the malevolent being thats wiping out her shipmates. But first she has to keep herself alive\"--Amazon.com.
Book
Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.
Journal Article
A clash of kings
FANTASY. George R.R. Martin's superb fantasy epic continues in consummate style as bloodshed and alchemy lay waste the Seven Kingdoms in the second volume of A Song of Ice and Fire. The Iron Throne once united the Sunset Lands, but King Robert is dead, his widow is a traitor to his memory, and his surviving brothers are set on a path of war amongst themselves. At King's Landing, the head of Lord Eddard Stark rots on a spike for all to see. His daughter Sansa is betrothed still to his killer's son Joffrey -- Queen Cersei's son, though not the son of her late husband Robert. Even so, Joffrey is now a boy-king, Cersei is his regent, and war is inevitable. In Dragonstone, Robert's brother Stannis has declared himself king, while his other brother Renly proclaims himself king at Storm's End -- and Eddard Stark's fifteen year old son Robb wears the crown of the north at Winterfell.
YIGSR, a Synthetic Laminin Pentapeptide, Inhibits Experimental Metastasis Formation
The invasion of tumor cells through basement membranes is a critical step in the formation of metastases. The binding of the malignant cells to laminin in the basement membranes allows their attachment and activates their invasiveness. Recently a synthetic nonapeptide from the B1 chain sequence of laminin was identified as a major site for cell binding. A pentapeptide within the nonapeptide sequence was found to reduce the formation of lung colonies in mice injected with melanoma cells and also to inhibit the invasiveness of the cells in vitro.
Journal Article