B cell responses to a peptide epitope. VI. The kinetics of antigen recognition modulates B cell-mediated recruitment of T helper subsets

The ability of Ag-primed B cells to recruit distinct Th subsets was examined using two analogous synthetic peptides, G41CT3 and G28CT3, as model Ags. With sequence differences at only two positions, these peptides were identical both with respect to fine specificity of Abs induced and ability to prime T cells. Lymph node cell populations primed with peptide G41CT3, when challenged with the homologous Ag, yielded predominantly Th2 cytokines. In contrast, a challenge with the heterologous Ag, G28CT3, resulted in a markedly increased production of Th1 cytokines. These distinctions derived from altered APC function of Ag-primed B cells due to differential kinetics of recognition of the two Ags by surface Ig receptors, as confirmed by binding studies with a panel of anti-G41CT3 mAbs. A concentration-dependent circular dichroism study revealed differences in the nature of intermolecular associations for these two peptides. Furthermore, the on-rate of peptide G28CT3 binding to Ab also increased with increasing peptide concentration, implying a dependence on intermolecular interactions. This, in turn, correlated well with the ability of peptide G28CT3 to preferentially activate either Th1 or Th2 cells. Thus, the relative proportion of Th1 vs Th2 cells recruited by Ag-primed B cells is governed by the on-rate of Ag binding to surface Ig receptors, with higher on-rates promoting Th1 recruitment. Further, even subtle changes in solution behavior of an Ag can markedly influence the kinetics of recognition by B cells

Scaling up studies on PEMFC using a modified serpentine flow field incorporating porous sponge inserts to observe water molecules

This is the final version. Available from MDPI via the DOI in this record. Flooding of the cathode flow channel is a major hindrance in achieving maximum performance from Proton Exchange Membrane Fuel Cells (PEMFC) during the scaling up process. Water accumulated between the interface region of Gas Diffusion Layer (GDL) and rib of the cathode flow field can be removed by the use of Porous Sponge Inserts (PSI) on the ribs. In the present work, the experimental investigations are carried out on PEMFC for the various reaction areas, namely 25, 50 and 100 cm2. Stoichiometry value of 2 is maintained for all experiments to avoid variations in power density obtained due to differences in fuel utilization. The experiments include two flow fields, namely Serpentine Flow Field (SFF) and Modified Serpentine with Staggered provisions of 4 mm PSI (4mm x 2mm x 2mm) Flow Field (MSSFF). The peak power densities obtained on MSSFF are 0.420 W/cm2, 0.298 W/cm2 and 0.232 W/cm2 compared to SFF which yields 0.242 W/cm2, 0.213 W/cm2 and 0.171 W/cm2 for reaction areas of 25, 50 and 100 cm2 respectively. Further, the reliability of experimental results is verified for SFF and MSSFF on 25 cm2 PEMFC by using Electrochemical Impedance Spectroscopy (EIS). The use of 4 mm PSI is found to improve the performance of PEMFC through the better water management.All India Council for Technical EducationDepartment of Science and Technology, New Delh

Using honey to heal diabetic foot ulcers

Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring

A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1.

Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10(-11)) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10(-9)). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology

A genome-wide association study of Hodgkin Lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21, and 10p14 (GATA3)

To identify predisposition loci for classical Hodgkin Lymphoma (cHL) we conducted a genome-wide association study of 589 cHL cases and 5,199 controls with validation in 4 independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL; odds ratio [OR]=1.22, Pcombined=1.91×10−8), 8q24.21 (rs2019960, PVT1; OR=1.33, Pcombined=1.26×10−13) and 10p14 (rs501764, GATA3; OR=1.25, Pcombined=7.05×10−8). Furthermore, we confirmed the role of the MHC in disease etiology by revealing a strong HLA association (rs6903608; OR=1.70, Pcombined=2.84×10−50). These data provide new insight into the pathogenesis of cHL