The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Are public subsidies effective for university spinoffs? Evidence from SBIR awards in the University of California system

This study examines the impact of public subsidies, and specifically, Small Business Innovation Research (SBIR) awards on university spinoff companies. Using unique data for a population of University of California spinoffs, we find pronounced differences between companies commercializing digital technologies (software and hardware), and those that focus on other product spaces. For digital spinoffs, receiving an SBIR award has a negative impact on raising venture capital and no impact on IPOs, exits or first sales. Conversely, for non-digital firms (e.g., biotechnology, energy), receiving an SBIR award has a positive effect on raising venture capital and performance outcomes. We reason that digital technologies are subject to faster cycle times and higher market uncertainty, relative to technological uncertainty. Digital firms may therefore benefit less from subsidies designed to support technology development, and private investors may view the need of digital companies to obtain such subsidies as a negative certification. Our findings inform policy by suggesting that the industrial domain may be an important boundary condition for the effectiveness of SBIR-type subsidies for university spinoffs

Right ventricular dysfunction after thrombolysis in patients with right ventricular infarction

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Mobile learning for the integration of groups that risk being marginalized

Social inclusion and cohesion are two of the objectives that the European Union has very often proclaimed in its documents, in the past ten years. At the same time, community policies have emphasized the role that ICTs can play to encourage and support participation and integration opportunities of disadvantaged citizens. Within this context, the ENSEMBLE project, presented here, aims at developing a strategy of use of ICTs to promote socio-cultural integration of immigrant citizens by using technologies such as MP3 players and mobile phones, and by experimenting instructional methods and communication models suitable for the adopted instruments. The present paper focuses particularly on the educational communication design of MMS messages

Bile acid structure-activity relationship: evaluation of bile acid lipophilicity using 1-octanol/water partition coefficient and reverse phase HPLC.

Two independent methods have been developed and compared to determine the lipophilicity of a representative series of naturally occurring bile acids (BA) in relation to their struc- ture. The BA included cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursocholic acid (UCA), hyocholic acid (HCA), as well as their glycine and taurine ami- dates. Lipophilicity was determined using a 1-octanol/water shake-flask procedure and the experiments were performed at different pH and ionic strengths and at initial BA concentrations below their critical micellar concentrations (CMC) and the water solubility of the protonated form. The experimental data show that both the protonated (HA) and ionized (A-) forms of BA can distribute in 1-octanol, and consequently a partition co- efficient for HA (logP' HA) and for A- (logP' A-) must be defined. An equation to predict a weighted apparent distribution coefficient (D) value as a function of pH and pKa has been de- veloped and fits well with the experimental data. Differences be- tween logP for protonated and ionized species for unconjugated BA were in the order of 1 log unit, which increased to 2 for glycine-amidated BA. The partition coefficient of the A- form in- creased with Na+ concentration and total ionic strength, suggest- ing an ion-pair mechanism for its partition into 1-octanol. Lipophilicity was also assessed using reverse phase chromatogra- phy (C-18-HPLC), and a capacity factor (K') for ionized species was determined. Despite a broad correlation with the logP data, some BA behaved differently. The logP values showed that the order of lipophilicity was DCA >CDCA >UDCA > HDCA > HCA>CA >UCA for both the protonated and ionized uncon- jugated and glycine-amidated BA, while the K' data showed an inversion for some BA, i.e., DCA>CDCA >CA> HCA> UDCA > HDCA >UCA. The logP data fitted well with other in- direct measurements of BA monomeric lipophilicity such as al- bumin binding or accessible total hydrophobic surface area data calculated by energy minimization and molecular computer graphics. Differences between unconjugated and amidated BA are consistent with the presence of an amide bond and a lower pKa when pH dependence was studied. Capacity factors, on the other hand, were related to properties of BA micelles such as cholesterol-solubilizing capacity and membrane disruption, reflecting the BA detergency. The extrapolation of these data to biological phenomena must carefully consider the experimental conditions in which the interaction occurs, Le., total BA concen- tration, ionic strength, Na+ concentration, and pH, which in turn determine the BA species existing in solution that coul