Rheumatoid Arthritis Susceptibility Is Associated with the KIR2DS4-Full of Killer-Cell Immunoglobulin-Like Receptor Genes in the Lur Population of Iran

Background:The pathophysiology underlying the progression and development of autoimmune conditions, such as Rheumatoid Arthritis (RA), is a result of dysregulations of the immune system. Research has explored the genetic alterations present in RA; however, limited studies have examined the role of Killer cell Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) molecules in RA. Therefore, the aim of this study was to examine KIR genes, their HLA ligands, and KIR-HLA compounds in patients with RA.Methods:In this case-control study, a total of 50 patients with RA and 100 healthy individuals were enrolled. DNA samples were evaluated using PCR with sequence specific Primers (PCR-SSP). Odds ratio (OR) with a 95% confidence interval (CI) were reported.Results:Among the KIR genes examined, KIR2DLA (p= 0.0255, OR= 0.389, 95% CI= 0.210-0.722) and KIR2DS4-full (p< 0.0001, OR= 6.163, 95% CI= 3.174-11.968) were observed to have a statistically significant correlation with disease susceptibility to RA. As an inhibitory gene, KIR2DLA was observed to have a protective effect against RA while KIR2DS4-full as an activating gene, was found to increase risk for RA. No significant associations were found between any of the other KIR genotypes, HLA ligands, or KIR-HLA compounds examined in this study to RA susceptibility. Conclusion:In this study of RA in the Lur population of Iran, KIR2DS4-full was observed to increase susceptibility to RA, while KIR2DL5A was found to act as a protecting factor based on both the cross Table and regression analyses. Further research should focus on repeating this study in additional populations.Key Words: HLA, KIR, NK cells, Rheumatoid Arthritis     

Determination of the extraction kinetics for the quantification of polyhydroxyalkanoate monomers in mixed microbial systems

For the first time, a systematic approach was conducted to determine the key factors influencing the kinetics of hydroxyalkanote (HA) extraction in biological systems. Six mixed microbial systems where polyhydroxyalkanoate (PHA) is produced were evaluated. Experiments were carried out for full-scale and lab-scale activated sludge systems using different configurations (containing floccular or granular sludge), as well as specific PHA accumulating cultures that contain high or low intracellular PHA fractions. The overall reaction was limited by the kinetics of the PHA hydrolysis in floccular cultures, whereas in granular cultures, it was limited by the cell lysis step. The monomeric composition of the polymer also had an impact on the HA extraction rate: higher acid concentration and a longer digestion time should be employed when cells accumulate monomers with more substituents, such as hydroxy-2-methylbutyrate (H2MB) and hydroxy-2-methylvalerate (H2MV). This study optimised the method for HA extraction, which impacts the assessment of the quantity and quality of PHA biopolymers.     

Antigenic Potency of LY6E in Stimulating Dendritic Cells to Elicit Tumor-Specific Responses Against Human Colorectal and Gastric Cancer Cell Lines

Early-stage gastrointestinal (GI) carcinomas are amenable malignancies, however, due to late diagnosis or lack of proper medication, alternative treatment necessitates new approaches such as dendritic cell (DC) therapy. Our previous microarray study indicated Lymphocyte antigen-6 (LY6E) as a commonly overexpressed biomarker in three lethal GI cancers, colon, gastric, and pancreatic. Therefore, we examined the antigenic potency of LY6E in stimulating DCs to elicit tumor-specific responses against human colorectal cancer (CRC) and gastric cancer (GC) cell lines HT-29 and AGS, respectively. LY6E peptide-pulsed DCs stimulated lymphocytes up to 55.9% in comparison with mature DCs (48.3%). Also, flow cytometry analysis of lymphocyte proliferation illustrated that the populations CD4⁺ and CD8⁺ were increased after treating by peptide-pulsed DCs (62.9% and 48.7% respectively). Furthermore, the cytotoxicity assay demonstrated that the 40:1 ratio of stimulated lymphocytes on AGS and HT29 cell lines was 65.1% and 66.2%, respectively. The research exposed that LY6E loaded DCs had substantial impact stimulation, proliferation, and lineage differentiation of lymphocytes. Besides, co-cultured of primed lymphocytes with AGS and HT29 cell lines exhibited cytotoxic activity. These data suggest LY6E as a potential candidate in developing DC therapy against CRC and AGS.

     

Two new collaborative filtering approaches to solve the sparsity problem

Cluster Computing - Collaborative filtering which is the most successful technique of the Recommender System, has recently attracted great attention, especially in the field of e-commerce. CF is...     

Re-emergence of Crimean-Congo hemorrhagic fever virus in Central Africa

Background

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne disease well recognized through Europe and Asia where diagnostic tests and medical surveillance are available. However, it is largely neglected in Africa, especially in the tropical rainforest of Central Africa where only sporadic human cases have been reported and date back to more than 30 years. We describe here an isolated human case that occurred in the Democratic Republic of the Congo in 2008 and performed phylogenetic analysis to investigate whether it resulted from a regional re-emergence or from the introduction of a novel virus in the area.

Methods and Findings

Near complete segment S and partial segment M sequences were characterized. Bayesian phylogenetic analysis and datation were performed to investigate the relationship between this new strain and viral strains from Africa, Europe and Asia. The new strain is phylogenetically close to the previously described regional genotype (II) that appears to be specific to Central Africa. Phylogenetic discrepancy between segment S and M suggested genetic exchange among local sublineages, which was dated back to 130–590 years before present.

Conclusions

The phylogenetic analyses presented here suggest ongoing CCHF virus circulation in Central Africa for a long time despite the absence of reported human cases. Many infections have most probably been overlooked, due to the weakness of healthcare structures and the absence of available diagnostic procedure. However, despite the lack of accurate ecological data, the sporadic reporting of human cases could also be partly associated with a specific sylvatic cycle in Central Africa where deforestation may raise the risks of re-emergence. For these reasons, together with the high risk of nosocomial transmission, public health authorities'' attention should be drawn to this etiological agent.     

Stain-Free total protein staining is a superior loading control to β-actin for Western blots

Semi-quantification of proteins using Western blots typically involves normalization against housekeeping genes such as β-actin. More recently, Ponceau S and Coomassie blue staining have both been shown to be suitable alternatives to housekeeping genes as loading controls. Stain-Free total protein staining offers the advantage of no staining or destaining steps. Evaluation of the use of Stain-Free staining as an alternative to β-actin or the protein stain Ponceau S showed that Stain-Free staining was superior to β-actin and as good as or better than Ponceau S staining as a loading control for Western blots.     

Telencephalic neural precursor cells show transient competence to interpret the dopaminergic niche of the embryonic midbrain

Neural Precursor Cells (NPCs) generate complex stereotypic arrays of neuronal subtypes in the brain. This process involves the integration of patterning cues that progressively restrict the fate of specific NPCs. Yet the capacity of NPCs to interpret foreign microenvironments during development remains poorly defined. The aim of this work was to test the competence of mouse telencephalic NPCs to respond to the dopaminergic niche of the mesencephalon. Telencephalic NPCs isolated from midgestation mouse embryos (E10.5) and transplanted to age-matched mesencephalic explants efficiently differentiated into neurons but were largely unable to produce midbrain dopaminergic (mDA) neurons. Instead, E10.5 telencephalic NPCs behaved as restricted gabaergic progenitors that maintained ectopic expression of Foxg1 and Pax6. In contrast, E8.5 telencephalic NPCs were able to differentiate into Lmx1a⁺/Foxa2⁺/TH⁺ neurons in the dopaminergic niche of the mesencephalic explants. In addition, these early telencephalic NPCs showed region-dependent expression of Nkx6.1, Nkx2.2 and site-specific differentiation into gabaergic neurons within the mesencephalic tissue. Significant dopaminergic differentiation of E8.5 telencephalic NPCs was not observed after transplantation to E12.5 mesencephalic explants, suggesting that inductive signals in the dopaminergic niche rapidly decay after midgestation. Moreover, we employed transplantation of embryonic stem cells-derived precursors to demonstrate that extinction of inductive signals within the telencephalon lags behind the commitment of residing NPCs. Our data indicate that the plasticity to interpret multiple instructive niches is an early and ephemeral feature of the telencephalic neural lineage.     

Landscape factors modulating patterns of salmonid distribution during summer in north Patagonian rivers

Understanding how ecosystem processes influencing fish distribution operate across spatial scales is important to understand biological invasions. Salmonids, originally from the Northern Hemisphere, have been repeatedly introduced throughout the world, making them an ideal group to test hypotheses about factors driving invasions. We assessed the influence of environmental variables at the watershed scale on the abundance and structure of salmonid assemblages in the breeding streams of the Upper Limay river basin, Rio Negro, Argentina. We combined field captures with digital map data and geographic information systems to examine landscape-level patterns of salmonid abundance in 35 representative sub-basins of the environmental gradient. We employed a hierarchical cluster analysis and classification and regression tree models to relate the abundance of salmonids and types of species assemblages with environmental characteristics at watershed level. We found stream localization, precipitation regime, altitude and air temperature to be important predictors of the abundance and assemblage structure of salmonids. Total catches showed an increasing gradient of catch-per-unit-effort from west to east and from north to south, with Oncorhynchus mykiss being the most abundant species. O. mykiss relative abundance was westward skewed, where smaller catchments with steeper and shaded valleys are drained by less productive streams with more irregular hydrological regimes, like those found in this species' North American native range. In contrast, the abundance of Salmo trutta abundance was eastward skewed, where larger, sunnier and more gently sloped catchments result in more productive streams with stable hydrological regimes, like those found in that species' European native range. Thus, differential salmonid abundance could result from the interplay between the evolutionary fingerprint left by each species' native environment (especially flow and temperature regimes) and the availability of those conditions in new environments to which they have been translocated. By furthering our understanding of how landscape conditioned invasion success, these findings can help guide the management of economically important introduced fish.