ICOS/ICOSL interaction is required for CD4+ invariant NKT cell function and homeostatic survival

The development of airway hyperreactivity (AHR), a cardinal feature of asthma, requires the presence of invariant NKT (iNKT) cells. In a mouse model of asthma, we demonstrated that the induction of AHR required ICOS costimulation of iNKT cells. ICOS was highly expressed on both naive and activated iNKT cells, and expression of ICOS was greater on the CD4(+) iNKT than on CD4(-) iNKT cells. Furthermore, the number of CD4(+) iNKT cells was significantly lower in spleens and livers of ICOS(-/-) and ICOSL(-/-) mice, and the remaining iNKT cells in ICOS(-/-) mice were dysfunctional and failed to reconstitute AHR when adoptively transferred into iNKT cell-deficient Jalpha18(-/-) mice. In addition, direct activation of iNKT cells with alpha-GalCer, which induced AHR in wild-type mice, failed to induce AHR in ICOS(-/-) mice. The failure of ICOS(-/-) iNKT cells to induce AHR was due in part to an inability of the ICOS(-/-) iNKT cells to produce IL-4 and IL-13 on activation. Moreover, survival of wild-type iNKT cells transferred into ICOSL(-/-) mice was greatly reduced due to the induction of apoptosis. These results indicate that ICOS costimulation plays a major role in induction of AHR by iNKT cells and is required for CD4(+) iNKT cell function, homeostasis, and survival in the periphery.     

Evaluation of random amplified polymorphic DNA analysis and antibiotic susceptibility application in discrimination of salmonella typhimurium isolates in Iran

The purpose of this study was to determine the utility of RAPD-PCR and antibiotic susceptibility tests in differentiation of S. typhimurium isolates in Iran. Thirty isolates of S. typhimurium, selected based on animal source; place and time of the isolation and a reference strain of the bacterium were used in this study. Serotyping of the isolates was performed by reliable antisera and confirmed with a multiplex PCR. Genomic DNAs were extracted and subjected to an optimized RAPD-PCR, using two previously reported arbitrary primers (P1254 and 23L). Bacteria were also examined for resistance against 8 antibiotics, using a standard antibiotic susceptibility test. While the antibiotic susceptibility test resulted in the identification of 13 profiles of R-type among the bacterial isolates, application of primers P1254 and 23L in the RAPD-PCR could discriminate the isolates only in four and six profiles respectively. However, combination of the two methods could differentiate the 30 isolates in 20 different profiles. The results of this study indicate that the discriminatory power of RAPD-PCR for S. typhimurium is low but a combination of this method with antibiotic susceptibility test could be considered an easy and relatively reliable discriminatory approach in differentiation of S. typhimurium for epidemiologic purposes in Iran.     

Artificial beta-sheets: chemical models of beta-sheets

Chemical models provide tools with which to simplify and study complicated biological systems. Forces and chemical processes that govern the structure, function, and interactions of a biomacromolecule can be explored with a simple, easy-to-study synthetic molecule. Chemical models of beta-sheet structures have helped to elucidate the factors influencing protein structures and functions. Chemical models that mimic beta-sheet quaternary structure and interactions are emerging as valuable tools with which to better understand and control protein recognition and protein aggregation.     

A new endogenous form of PYY isolated from canine ileum: Gly-extended PYY(1-36)

We purified and identified the peptide YY (PYY) forms present and determined their levels from a portion of the canine ileum directly adjacent to the cecum by a new extraction method designed to prevent and evaluate degradation of endogenous peptides. We used three reverse phase chromatography steps with radioimmunoassay of fractions for PYY-like-immunoreactivity (PYY-LI). The purified fractions underwent intact protein/peptide mass spectrometry identification and sequencing (i.e. "top-down" MS analysis). This analysis confirmed the identity of a new form of PYY, PYY(1-36)-Gly, which co-elutes with PYY(1-36)-NH(2) through all three of separation steps used. The PYY(1-36)-Gly form represents approximately 20% of the total PYY found in this region of the canine intestine. In addition, we also found that the PYY(3-36)-NH(2) form represents 6% of the total PYY in the canine ileo-cecal junction. The physiological implication of the Gly-extended form of PYY(1-36) warrants further investigation.     

Nanotechnology and aptamers: applications in drug delivery

Nucleic acid ligands, also known as aptamers, are a class of macromolecules that are being used in several novel nanobiomedical applications. Aptamers are characterized by high affinity and specificity for their target, a versatile selection process, ease of chemical synthesis and a small physical size, which collectively make them attractive molecules for targeting diseases or as therapeutics. These properties will enable aptamers to facilitate innovative new nanotechnologies with applications in medicine. In this review, we will highlight recent developments in using aptamers in nanotechnology solutions for treating and diagnosing disease.