IFN-γ and TNF-α synergize to inhibit CTGF expression in human lung endothelial cells.

Connective tissue growth factor (CTGF/CCN2) is an angiogenetic and profibrotic factor, acting downstream of TGF-β, involved in both airway- and vascular remodeling. While the T-helper 1 (Th1) cytokine interferon-gamma (IFN-γ) is well characterized as immune-modulatory and anti-fibrotic cytokine, the role of IFN-γ in lung endothelial cells (LEC) is less defined. Tumour necrosis factor alpha (TNF-α) is another mediator that drives vascular remodeling in inflammation by influencing CTGF expression. In the present study we investigated the influence of IFN-γ and TNF-α on CTGF expression in human LEC (HPMEC-ST1.6R) and the effect of CTGF knock down on human LEC. IFN-γ and TNF-α down-regulated CTGF in human LEC at the promoter-, transcriptional- and translational-level in a dose- and time-dependent manner. The inhibitory effect of IFN-γ on CTGF-expression could be almost completely compensated by the Jak inhibitor AG-490, showing the involvement of the Jak-Stat signaling pathway. Besides the inhibitory effect of IFN-γ and TNF-α alone on CTGF expression and LEC proliferation, these cytokines had an additive inhibitory effect on proliferation as well as on CTGF expression when administered together. To study the functional role of CTGF in LEC, endogenous CTGF expression was down-regulated by a lentiviral system. CTGF silencing in LEC by transduction of CTGF shRNA reduced cell proliferation, but did not influence the anti-proliferative effect of IFN-γ and TNF-α. In conclusion, our data demonstrated that CTGF was negatively regulated by IFN-γ in LEC in a Jak/Stat signaling pathway-dependent manner. In addition, an additive effect of IFN-γ and TNF-α on inhibition of CTGF expression and cell proliferation could be found. The inverse correlation between IFN-γ and CTGF expression in LEC could mean that screwing the Th2 response to a Th1 response with an additional IFN-γ production might be beneficial to avoid airway remodeling in asthma

Pressure and Temperature Effect on Hydrogen Sorption of Carbon Material

The paper presents the experimental results of saturation of the carbon material containing nanotubes with hydrogen from the gas. The dependences of hydrogen concentration from pressure (from 0 to 8 atmospheres), at the same temperature for adsorption (-30 degrees Celsius) and different temperatures for desorption were obtained. The temperature has an influence on sorption-desorption process and sorption properties of carbon material. The amount of residual hydrogen depends on saturation parameters

Efficient determination of cysteine sulphoxides in Allium plants applying new biosensor and HPLC-MS² methods

Cysteine sulphoxide (CSO) contents of 16 different accessions of garlic (Allium sativum L.) and 15 varieties of onion (Allium cepa L.) were measured using two different rapid analytical methods: a biosensoric approach and a newly developed HPLC-MS2 technique. Both methods allow quantification of naturally occurring cysteine sulphoxides present in Allium plants without time-consuming sample pretreatment such as derivatisation of amino acid derivatives prior to HPLC-separation. It has been found that the amount of alliin, which is the predominant CSO occurring in garlic, varies between 0.2 and 2.2 g/100 g dry matter. Contrary to that, isoalliin representing the main CSO in onion has been detected in significantly lower amounts (0.3 to 1.25 g/100 g dry matter)

Особенности налогообложения в розничной торговле

Объектом исследования является: ИП Хорева специализирующееся на розничной торговле изделиями из меха и кожи. Цель работы – анализ деятельности предприятия, определение основных показателей его экономической деятельности, расчет налогов, расчет и анализ налоговой нагрузки предприятия. В процессе исследования проводились: создание теоретической базы для анализа экономической деятельности предприятия, непосредственно анализ экономической деятельности, расчёт и анализ налоговой нагрузки предприятия. В результате исследования выработаны конкретные рекомендации по оптимизации экономической деятельности предприятия.The object of research is: IP Khoreva specializing in the retail sale of fur and leather products. The purpose of the work is the analysis of the enterprise, determining the main indicators of its economic activity, tax calculation, calculation and analysis of the tax burden of the enterprise. In the course of the research, the following was carried out: creation of a theoretical base for analysis of the economic activity of an enterprise, direct analysis of economic activity, calculation and analysis of the tax burden of the enterprise. As a result of the study, specific recommendations were developed to optimize the economic activity of the enterprise

Application of shotgun metagenomics sequencing and targeted sequence capture to detect circulating porcine viruses in the Dutch-German border region

Porcine viruses have been emerging in recent decades, threatening animal and human health, as well as economic stability for pig farmers worldwide. Next-generation sequencing (NGS) can detect and characterize known and unknown viruses but has limited sensitivity when an unbiased approach, such as shotgun metagenomics sequencing, is used. To increase the sensitivity of NGS for the detection of viruses, we applied and evaluated a broad viral targeted sequence capture (TSC) panel and compared it to an unbiased shotgun metagenomic approach. A cohort of 36 pooled porcine nasal swab and blood serum samples collected from both sides of the Dutch-German border region were evaluated. Overall, we detected 46 different viral species using TSC, compared to 40 viral species with a shotgun metagenomics approach. Furthermore, we performed phylogenetic analysis on recovered influenza A virus (FLUAV) genomes from Germany and revealed a close similarity to a zoonotic influenza strain previously detected in the Netherlands. Although TSC introduced coverage bias within the detected viruses, it improved sensitivity, genome sequence depth and contig length. In-depth characterization of the swine virome, coupled with developing new enrichment techniques, can play a crucial role in the surveillance of circulating porcine viruses and emerging zoonotic pathogens

Intramuscular DNA Vaccination of Juvenile Carp against Spring Viremia of Carp Virus Induces Full Protection and Establishes a Virus-Specific B and T Cell Response

Although spring viremia of carp virus (SVCV) can cause high mortalities in common carp, a commercial vaccine is not available for worldwide use. Here, we report a DNA vaccine based on the expression of the SVCV glycoprotein (G) which, when injected in the muscle even at a single low dose of 0.1 µg DNA/g of fish, confers up to 100% protection against a subsequent bath challenge with SVCV. Importantly, to best validate vaccine efficacy, we also optimized a reliable bath challenge model closely mimicking a natural infection, based on a prolonged exposure of carp to SVCV at 15°C. Using this optimized bath challenge, we showed a strong age-dependent susceptibility of carp to SVCV, with high susceptibility at young age (3 months) and a full resistance at 9 months. We visualized local expression of the G protein and associated early inflammatory response by immunohistochemistry and described changes in the gene expression of pro-inflammatory cytokines, chemokines, and antiviral genes in the muscle of vaccinated fish. Adaptive immune responses were investigated by analyzing neutralizing titers against SVCV in the serum of vaccinated fish and the in vitro proliferation capacity of peripheral SVCV-specific T cells. We show significantly higher serum neutralizing titers and the presence of SVCV-specific T cells in the blood of vaccinated fish, which proliferated upon stimulation with SVCV. Altogether, this is the first study reporting on a protective DNA vaccine against SVCV in carp and the first to provide a detailed characterization of local innate as well as systemic adaptive immune responses elicited upon DNA vaccination that suggest a role not only of B cells but also of T cells in the protection conferred by the SVCV-G DNA vaccine

NH3-SCR catalysts for heavy-duty diesel vehicles: Preparation of CHA-type zeolites with low-cost templates

Computer-assistance allows selecting the most adequate low-cost organic structure directing agents (OSDAs) for the crystallization of Al-rich CHA-type zeolites. The host-guest stabilization energies of tetraethylammonium (TEA), methyltriethylammonium (MTEA) and dimethyldiethylammonium (DMDEA), in combination with Na, were first theoretically evaluated. This “ab-initio” analysis reveals that two TEA show a serious steric hindrance in a cha cavity, whereas two MTEA would present excellent host-guest confinements. The synthesis of Al-rich CHA-type zeolites has been accomplished using TEA and MTEA. Electron diffraction and high-resolution transmission electron microscopy reveal large CHA-domains with narrow faulted GME-domains in the CHA-type material synthesized with TEA, confirming the better OSDA-directing roles of MTEA cations towards the cha cavity, in good agreement with DFT calculations. Cu-exchanged Al-rich CHA-type samples achieved with MTEA and TEA show excellent catalytic activity and hydrothermal stability for the selective catalytic reduction (SCR) of NOx with ammonia under conditions relevant for future heavy duty diesel conditions.This work has been supported by Umicore and by the Spanish Government-MCIU through RTI2018-101033-B-I00 (MCIU/AEI/FEDER, UE) and PID2020-112590GB-C21 (AEI/FEDER, UE). T.W. acknowledges financial support by the Swedish Research Council (Grant No. 2019-05465). E.B. acknowledges the Spanish Government-MCIU for a FPI scholarship (PRE2019-088360). P.F. thanks ITQ for a contract. The Electron Microscopy Service of the UPV is acknowledged for their help in sample characterization. The computations were performed on the Tirant III cluster of the Servei d'Informàtica of the University of Valencia

Calculation of critical loads for cadmium, lead and mercury; background document to a mapping manual on critical loads of cadmium, lead and mercury

This report on heavy metals provides up-to-date methodologies to derive critical loads for the heavy metals cadmium (Cd), lead (Pb) and mercury (Hg) for both terrestrial and aquatic ecosystems. It presents background information to a Manual on Critical Loads for those metals. Focus is given to the methodologies and critical limits that have to be used to derive critical loads can be derived for Cd, Pb and Hg in view of : (i) ecotoxicological effects for either terrestrial or aquatic ecosystems.and (ii) human health effects for either terrestrial or aquatic ecosystems. For Hg, a separate approach is described to estimate critical levels in precipitation in view of human health effects due to the consumption of fish. The limitations and uncertainties of the approach are discussed including: (i) the uncertainties and particularities of the steady-state models used and (ii) the reliability of the approaches that are applied to derive critical limits for critical total dissolved metal concentrations in soil solution and surface wate