A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.     

UPR: deadlock-free dynamic network reconfiguration by exploiting channel dependency graph compatibility

The Journal of Supercomputing - Deadlock-free dynamic network reconfiguration process is usually studied from the routing algorithm restrictions and resource reservation perspective. The dynamic...     

Visibility of collaboration on the Web

The emerging influence of new information and communication technologies (ICT) on collaboration in science and technology has to be considered. In particular, the question of the extent to which collaboration in science and in technology is visible on the Web needs examining. Thus the purpose of this study is to examine whether broadly similar results would occur if solely Web data was used rather than all available bibliometric co-authorship data. For this purpose a new approach of Web visibility indicators of collaboration is examined. The ensemble of COLLNET members is used to compare co-authorship patterns in traditional bibliometric databases and the network visible on the Web. One of the general empirical results is a high percentage (78%) of all bibliographic multi- authored publications become visible through search of engines in the Web. One of the special studies has shown Web visibility of collaboration is dependent on the type of bibliographic multi-authored papers. The social network analysis (SNA) is applied to comparisons between bibliographic and Web collaboration networks. Structure formation processes in bibliographic and Web networks are studied. The research question posed is to which extent collaboration structures visible in the Web change their shape in the same way as bibliographic collaboration networks over time. A number of special types of changes in bibliographic and Web structures are explained. This revised version was published online in June 2006 with corrections to the Cover Date.     

Effects of Sc2O3 and MgO passivation layerson the output power of AlGaN/GaN HEMTs

The low temperature (100°C) deposition of Sc₂O₃ or MgO layers is found to significantly increase the output power of AlGaN/GaN HEMTs. At 4 GHz, there was a better than 3 dB increase in output power of 0.5×100 μm² HEMTs for both types of oxide passivation layers. Both Sc₂ O₃ and MgO produced larger output power increases at 4 GHz than conventional plasma-enhanced chemical vapor deposited (PECVD) SiN_x passivation which typically showed ⩽2 dB increase on the same types of devices. The HEMT gain also in general remained linear over a wider input power range with the Sc₂O₃ or MgO passivation. These films appear promising for reducing the effects of surface states on the DC and RF performance of AlGaN/GaN HEMTs     

Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrP^C), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrP^C and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrP^C and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrP^C ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrP^C expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrP^C levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrP^C in this phenomenon. Our results indicate that PrP^C plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.     

Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase

Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure-based virtual screening of FDA-approved drugs was performed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05–4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).     

Effect of low-sulfur fuels upon NH3 and N2O emission during operation of commercial three-way catalytic converters

The use of low-sulfur fuel is known to improve the performance of the three-way catalytic converter (TWC). However, in this work we report how low-sulfur operation of commercial TWC also favors formation of N₂O and NH₃ as by products. We found that low-sulfur rich operation above 300 °C increases the production of NH₃, inhibiting the formation of N₂O characteristic of high-sulfur operation. During lean operation, the production of N₂O near the stoichiometric point is not significantly affected by the sulfur level. The large production of N₂O observed during light-off is not affected by SO₂ when the operation is lean, but under rich conditions N₂O is produced up to 575 °C. The increased production of NH₃ and N₂O in TWC as a result of the introduction of low-sulfur gasoline is an area that requires further analysis because of its implication upon public health in large urban settings.