On the contribution of twist-3 multi-gluon correlation functions to single transverse-spin asymmetry in SIDIS

We study the single spin asymmetry (SSA) induced by purely gluonic correlation inside a nucleon, in particular, by the three-gluon correlation functions in the transversely polarized nucleon, $p^\uparrow$. This contribution is embodied as a twist-3 mechanism in the collinear factorization framework and controls the SSA to be observed in the $D$-meson production with large transverse-momentum in semi-inclusive DIS (SIDIS), $ep^\uparrow \rightarrow eDX$. We define the relevant three-gluon correlation functions in the nucleon, and determine their complete set at the twsit-3 level taking into account symmetry constraints in QCD. We derive the single-spin-dependent cross section for the $D$-meson production in SIDIS, taking into account all the relevant contributions at the twist-3 level. The result is obtained in a manifestly gauge-invariant form as the factorization formula in terms of the three-gluon correlation functions and reveals the five independent structures with respect to the dependence on the azimuthal angle for the produced $D$ meson. We also demonstrate the remarkable relation between the twist-3 single-spin-dependent cross section and twist-2 cross sections for the $D$-meson production, as a manifestation of universal structure behind the SSA in a variety of hard processes.Comment: 8 pages, 2 figures. To appear in the proceedings of the 19th International Spin Physics Symposium (SPIN2010), Juelich, Germany, Sept.27 - Oct.2, 201

Gauge links for transverse momentum dependent correlators at tree-level

In this paper we discuss the incorporation of gauge links in hadronic matrix elements that describe the soft hadronic physics in high energy scattering processes. In this description the matrix elements appear in soft correlators and they contain non-local combinations of quark and gluon fields. In our description we go beyond the collinear approach in which case also the dependence on transverse momenta of partons is taken into consideration. The non-locality in the transverse direction leads to a complex gauge link structure for the full process, in which color is entangled, even at tree-level. We show that at tree-level in a 1-parton unintegrated (1PU) situation, in which only the transverse momentum of one of the initial state hadrons is relevant, one can get a factorized expression involving transverse momentum dependent (TMD) distribution functions. We point out problems at the level of two initial state hadrons, even for relatively simple processes such as Drell-Yan scattering.Comment: 25 pages, corrected typos and updated reference

Transverse Momentum Dependent Parton Distribution/Fragmentation Functions at an Electron-Ion Collider

We present a summary of a recent workshop held at Duke University on Partonic Transverse Momentum in Hadrons: Quark Spin-Orbit Correlations and Quark-Gluon Interactions. The transverse momentum dependent parton distribution functions (TMDs), parton-to-hadron fragmentation functions, and multi-parton correlation functions, were discussed extensively at the Duke workshop. In this paper, we summarize first the theoretical issues concerning the study of partonic structure of hadrons at a future electron-ion collider (EIC) with emphasis on the TMDs. We then present simulation results on experimental studies of TMDs through measurements of single spin asymmetries (SSA) from semi-inclusive deep-inelastic scattering (SIDIS) processes with an EIC, and discuss the requirement of the detector for SIDIS measurements. The dynamics of parton correlations in the nucleon is further explored via a study of SSA in D (`D) production at large transverse momenta with the aim of accessing the unexplored tri-gluon correlation functions. The workshop participants identified the SSA measurements in SIDIS as a golden program to study TMDs in both the sea and valence quark regions and to study the role of gluons, with the Sivers asymmetry measurements as examples. Such measurements will lead to major advancement in our understanding of TMDs in the valence quark region, and more importantly also allow for the investigation of TMDs in the sea quark region along with a study of their evolution.Comment: 44 pages 23 figures, summary of Duke EIC workshop on TMDs accepted by EPJ

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Diverse basis of β-catenin activation in human hepatocellular carcinoma: Implications in biology and prognosis

Aim: β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ϵ (CK1ϵ) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC. Methods: Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues. Results: Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001). Conclusion: This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism

Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor

Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity

Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma

We sought to identify a secreted biomarker for β-catenin activation commonly seen in hepatocellular carcinoma (HCC). By examination of our previously published genearray of hepatocyte-specific β-catenin knockout (KO) livers, we identified secreted factors whose expression may be β-catenin-dependent. We verified expression and secretion of the leading factor in HCC cells transfected with mutated (Hep3BS33Y)-β- catenin. Serum levels of biomarker were next investigated in a mouse model of HCC with β-catenin gene (Ctnnb1) mutations and eventually in HCC patients. Leukocyte cell-derived chemotaxin-2 (LECT2) expression was decreased in KO livers. Hep3BS33Y expressed and secreted more LECT2 in media as compared to Hep3BWT. Mice developing HCC with Ctnnb1 mutations showed significantly higher serum LECT2 levels. However patients with CTNNB1 mutations showed LECT2 levels of 54.28±22.32 ng/mL (Mean ± SD; n = 8) that were insignificantly different from patients with non-neoplastic chronic liver disease (32.8±21.1 ng/mL; n = 15) or healthy volunteers (33.2±7.2 ng/mL; n = 11). Intriguingly, patients without β-catenin mutations showed significantly higher serum LECT2 levels (54.26 ± 22.25 ng/mL; n = 46). While β-catenin activation was evident in a subset of non-mutant β-catenin HCC group with high LECT2 expression, serum LECT2 was unequivocally similar between β-catenin-active and -normal group. Further analysis showed that LECT2 levels greater than 50 ng/ml diagnosed HCC in patients irrespective of β-catenin mutations with specificity of 96.1% and positive predictive value of 97.0%. Thus, LECT2 is regulated by β-catenin in HCC in both mice and men, but serum LECT2 reflects β-catenin activity only in mice. Serum LECT2 could be a potential biomarker of HCC in patients. © 2014 Okabe et al

Dietary algae and HIV/AIDS: proof of concept clinical data

Dietary algae have been reported to decrease HIV viral fusion/entry and replication and increase immune response, suggesting that regular consumption of algae by people in Japan, Korea, and Chad could be an important factor in their relatively low HIV/AIDS rates. Five antiretroviral-naïve people with HIV (three females, two males; five African Americans) living in Columbia SC participated in the phase I study of acute toxicity. Subjects were randomly assigned to 5 g day-1 brown seaweed (Undaria pinnatifida), Spirulina (Arthrospira platensis), or a combination of both. Endpoints included HIV viral load, complete blood count (CBC), metabolic and lipid panel, and quality of life questionnaire data. When no short-term toxicities were observed, six additional subjects (four females, two males; five African Americans, one Latina) were recruited to further evaluate short- and long-term toxicities (phase II). No adverse effects were observed for the 11 subjects in the phase I trial, and quality of life indicators improved at 3 weeks. No significant changes were observed in CBC, metabolic or lipid panel analyses. CD4 cells (milliliters) and HIV-1 viral load remained stable over the first 3-month phase II study period. One subject continued in the study for 13 months and had clinically significant improvement in CD4 (>100 cells mL−1) and decreased HIV viral load of 0.5 log10. Our pilot data suggest that Undaria, Spirulina, and a combination of both were nontoxic and over time may improve clinical endpoints of HIV/AIDS

Neutrophil elastase reduces secretion of secretory leukoproteinase inhibitor (SLPI) by lung epithelial cells: role of charge of the proteinase-inhibitor complex

<p>Abstract</p> <p>Background</p> <p>Secretory leukoproteinase inhibitor (SLPI) is an important inhibitor of neutrophil elastase (NE), a proteinase implicated in the pathogenesis of lung diseases such as COPD. SLPI also has antimicrobial and anti-inflammatory properties, but the concentration of SLPI in lung secretions in COPD varies inversely with infection and the concentration of NE. A fall in SLPI concentration is also seen in culture supernatants of respiratory cells exposed to NE, for unknown reasons. We investigated the hypothesis that SLPI complexed with NE associates with cell membranes <it>in vitro</it>.</p> <p>Methods</p> <p>Respiratory epithelial cells were cultured in the presence of SLPI, varying doses of proteinases over time, and in different experimental conditions. The likely predicted charge of the complex between SLPI and proteinases was assessed by theoretical molecular modelling.</p> <p>Results</p> <p>We observed a rapid, linear decrease in SLPI concentration in culture supernatants with increasing concentration of NE and cathepsin G, but not with other serine proteinases. The effect of NE was inhibited fully by a synthetic NE inhibitor only when added at the same time as NE. Direct contact between NE and SLPI was required for a fall in SLPI concentration. Passive binding to cell culture plate materials was able to remove a substantial amount of SLPI both with and without NE. Theoretical molecular modelling of the structure of SLPI in complex with various proteinases showed a greater positive charge for the complex with NE and cathepsin G than for other proteinases, such as trypsin and mast cell tryptase, that also bind SLPI but without reducing its concentration.</p> <p>Conclusion</p> <p>These data suggest that NE-mediated decrease in SLPI is a passive, charge-dependent phenomenon <it>in vitro</it>, which may correlate with changes observed <it>in vivo</it>.</p