Defensins couple dysbiosis to primary immunodeficiency in Crohn's disease

Antimicrobial peptides,including defensins,are essential effectors in host defence and in the maintenance of immune homeostasis.Clinical studies have linked the defective expression of both α-and β-defensin to the reduced killing of certain microorganisms by the intestinal mucosa of patients suffering from ileal and colonic Crohn's disease(CD),respectively.Only recently have the events leading to defective expression of defensins in CD been further elucidated,and are discussed herein.These events may account for CD-associated alterations in the microbiome and may subsequently precipitate the development of granulomatous inflammatory lesions in genetically-predisposed patients.We also address how these discoveries may pave the way for the development of a molecular medicine aimed at restoring gut barrier function in CD.

Oxidative dehydrogenation of propane under steady-state and transient regimes over alumina-supported catalysts prepared from mixed V_2W_4O_(19)^(4-) hexametalate precursors

An integrated approach combining the development of an innovative catalyst and the research of a set of adequate operating conditions for the propane oxidative dehydrogenation （ODH） is described.The experimental set-up,specially designed for steady-state and transient studies is presented.The preparation method,the characterization and the performances in steady-state and transient regimes of catalysts based on V2W4O194-Lindqvist isopolyanion used as a precursor and supported on alumina are reported.The influence of the preparation method of the catalyst and the role of water in the feed gas are more particularly discussed.

Cracking of S235JR Cold-Deformed Steel during Galvanizing—Developing a Test to Evaluate and Predict the Effect of the Zinc Alloy Composition

This paper presents a study on the cracking of steel pieces during their galvanization in alloyed liquid zinc. An experimental design was developed to show the effect of the amount of the various alloying elements (Sn, Bi, Pb) on this phenomenon. The characterization of the effect was obtained by 1) deformation by three-point bending of a piece of steel with different levels of deflection;2) galvanizing and 3) observation and measurement of the cracks. A model of the critical deflection (deflection for crack starting) with the amounts of Sn, Pb, and Bi is presented and the predictions are described.

HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

AIM:To analyze hepatitis C virus(HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α(IFN-α)plus ribavirin and CIGB-230.METHODS:CIGB-230 was administered in different schedules with respect to IFN-αplus ribavirin therapy.Paired serum and peripheral blood mononuclear cells(PBMC)samples from baseline and end of treatment were analyzed.The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay,neutralizing antibodies were evaluated by cell culture HCV neutralization assays,PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γsecretion was assessed by enzyme-linked immunospot.Data on virological and histological response and their association with immune variables are also provided.RESULTS:From week 12 to week 48,all groups of patients showed a significant reduction in mean leukocyte counts.Statistically significant reductions in antibody titers were frequent,but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response,and the neutralizing antibody response was enhanced only in patients receiving CIGB-230.Cell-mediated immune responses also tended to decline,but significant reductions in IFN-γsecretion and total absence of core-specific lymphoproliferation were exclusive of the control group.Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens.Importantly,it was demonstrated that thequality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy.Specifically,the administration of 6 doses of CIGB-230 as late addon to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γsecretion,both of which were associated with the sustained virological response.CONCLUSION:CIGB-230,combined with IFN-α-based therapy,modifies the immune response in chronic patients.The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV.

Preliminary Characterizations of a Carbohydrate from the Concentrated Culture Filtrate from <i>Fusarium solani</i>and Its Role in Benzo[a]Pyrene Solubilization

In order to investigate the mechanism of benzo[a]pyrene uptake by a filamentous fungus Fusarium solani, a biochemical characterization of its concentrated culture filtrate has been conducted. The preparation contained approximately (w/w): 50% of total carbohydrate, 6.5% of uronic acid and 6% protein, as determined by colorimetric tests. Gel filtration and anion-exchange chromatographic profiles indicated that the main product of the culture filtrate was a glycoprotein, which contained mannose, glucose and galactose in an approximate molar ratio of 1.5: 0.8: 1. The polysaccharide fraction of the culture filtrate was prepared by treatment with proteinase K, followed by gel-filtration chromatography. Its chemical structure was studied by methylation analysis, gas-liquid chromatography-mass spectrometry (GC-MS) and Nuclear Magnetic Resonance spectroscopy (NMR). The major carbohydrate was a polymer of β-(1 → 6)-linked galactofuranose units fully branched at positions O-2 by single residues of α-glucopyranose. The Fusarium concentrated culture filtrate increased 4-fold the BaP solubilization in comparison with its aqueous solubility and suggested that the carbohydrate present in this filtrate should probably be involved in this enhancement. Our findings point out the potential role of fungal glycoproteins in PAH microbial bioavaibility, an important step for PAH biodegradation.

GUIDED WAVES IN MULTILAYERED PLATES: AN IMPROVED ORTHOGONAL POLYNOMIAL APPROACH

Conventional orthogonal polynomial approach can solve the multilayered plate only when the material properties of two adjacent layers do not change significantly. This paper de- veloped an improved orthogonal polynomial approach to solve wave propagation in multilayered plates with very dissimilar material properties. Through numerical comparisons among the exact solution, the results from the conventional polynomial approach and from the improved poly- nomial approach, the validity of the improved polynomial approach is illustrated. Finally, it is shown that the conventional polynomial approach can not yield correct continuous normal stress profiles. The improved orthogonul polynomial approach has overcome this drawback.

Neuroendocrine control of natural killer cell function through the checkpoint molecule PD-1

Host defense strategies encompass resistance to reduce pathogen burden,and disease tolerance to preserve host fitness.1 Immunedriven resistance mechanisms have inevitably a negative impact on host fitness and can lead to immunopathology.Disease tolerance limit immunopathology and therefore disease severity by preventing tissue damage or ameliorating tissue function without interfering with pathogen load.Several pathways cooperate to protect the host.These pathways include metabolic and oxidative stress responses,2 and the interaction between neuroendocrine system and the immune system3 to favor resolution of inflammation and to prevent tissue damage.

DIELECTRIC AND PIEZOELECTRIC PROPERTIES OF LEAD-FREE(Bi_(0.5)Na_(0.5))_(0.94)Ba_(0.06)TiO_(3)+x%Ce_(2)O_(3)+y%La_(2)O_(3)+z%Y_(2)O_(3) COMPOUNDS SYNTHESIZED BY SOL-GEL TECHNIQUE

(Bi_(0.5)Na_(0.5))_(0.94)Ba_(0.06)TiO_(3)+x%Ce_(2)O_(3)+y%La_(2)O_(3)+z%Y_(2)O_(3) compounds(named BNT-BT-x/y/z)were synthesized by a sol-gel technique,for (x,y,z)=(0,0,0),(0.25,0.25,0.25),(0.25,0.5,0.5),(0.5,0.25,0.25)and(0.5,0.5,0.25).The structural variation according to the different system compositions is investigated by X-ray diffraction analyses.The results shows that the addition of Ce_(2)O_(3),La_(2)O_(3) or Y_(2)O_(3) in BNT-BT system,do not modify the crystalline structure,and a rhombohedral-tetragonal morphotropic phase boundary is maintained for different dopant addition.The BNT-BT-x/y/z-based ceramics sintered at relatively low temperature(1100℃)exhibit a good densification ratio.The optimum dielectric and piezoelectric properties are obtained with the BNT-BT-0.5/0.25/0.25 composition.High dielectric properties at room temperature(ε_(r)>1000)and low dielectric losses(tanδ<4×10^(-2))are obtained for this composition.This compound exhibits a piezoelectric constant d_(33) of 95 pC/N,a good polarization behavior is observed with high remanent polarization P_(r) of 9.21μC/cm^(2) and low value coercitivefield E_(c) of 2.66 kV/mm.