Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo

In the steady state, interaction between T cells and antigen-presenting dendritic cells (DCs) leads to T cell tolerance. To examine the role of DC regulated peripheral tolerance in a model autoimmune disease, we delivered an encephalitogenic oligodendrocyte glycoprotein (MOG) peptide to DCs in vivo. We found that targeting MOG peptide to DCs resulted in a novel form of peripheral T cell tolerance that was sufficiently profound to prevent autoimmune experimental acute encephalomyelitis (EAE). The tolerized T cells were severely impaired in specific secondary responses to antigen in vivo but they were not intrinsically anergic since they remained highly responsive to T cell receptor (TCR) stimulation in vitro. The mechanism that mediates this dynamic antigen-specific T cell unresponsiveness differs from previously described forms of tolerance in that it requires that DCs induce CD5 expression on activated T cells.     

The case of the missing girls: distribution of gender roles in Indian children’s television programming

Children’s programming is booming in India with children having increased access to television. Given that television is a powerful socializing agent, this study seeks to identify how gender is being represented in it using content analysis. The gender and role of 826 major characters across 89 programmes, which were telecast on 11 channels during the evenings, was analysed. The results show that 91.01% of all the programmes were animated. There was a gender bias in the programme titles, as the majority contained only male or gender-neutral names. Males (74.94%) outnumber females (25.06%) across all channels, irrespective of their target audience. More males than females were cast in all the character roles except in the role of the protagonist’s family member, where both genders were cast equally. The underrepresentation of females in some character roles also veered towards 100% on certain channels. Overall, most programmes seem oriented towards boys than girls.     

Pseudomonas Exotoxin A Based Toxins Targeting Epidermal Growth Factor Receptor for the Treatment of Prostate Cancer

The epidermal growth factor receptor (EGFR) was found to be a valuable target on prostate cancer (PCa) cells. However, EGFR inhibitors mostly failed in clinical studies with patients suffering from PCa. We therefore tested the targeted toxins EGF-PE40 and EGF-PE24mut consisting of the natural ligand EGF as binding domain and PE40, the natural toxin domain of Pseudomonas Exotoxin A, or PE24mut, the de-immunized variant thereof, as toxin domains. Both targeted toxins were expressed in the periplasm of E.coli and evoked an inhibition of protein biosynthesis in EGFR-expressing PCa cells. Concentration- and time-dependent killing of PCa cells was found with IC₅₀ values after 48 and 72 h in the low nanomolar or picomolar range based on the induction of apoptosis. EGF-PE24mut was found to be about 11- to 120-fold less toxic than EGF-PE40. Both targeted toxins were more than 600 to 140,000-fold more cytotoxic than the EGFR inhibitor erlotinib. Due to their high and specific cytotoxicity, the EGF-based targeted toxins EGF-PE40 and EGF-PE24mut represent promising candidates for the future treatment of PCa.     

Protein tyrosine phosphatase inhibitors: a patent review (2002 - 2011)

INTRODUCTION: The protein tyrosine phosphatases (PTPases or PTPs) are highly conserved phosphatases that regulate the tyrosine phosphorylation and consequently, the cellular functions. Protein tyrosine phosphorylation is the major post-translational modification to regulate signal transduction in cells. PTPs control diverse processes such as focal adhesion dynamics, cell-cell adhesion, insulin signaling, cytoskeletal functions, synaptogenesis and neurite growth. The availability of numerous X-ray crystal structures of PTPs, along with their inhibitors, has provided the opportunity for the structure-based design of effective inhibitors having potential for the treatment of various disorders. AREAS COVERED: The main focus of the present review is to get an insight into the most clinically relevant therapeutic PTP inhibitors published in patents over the past 10 years. EXPERT OPINION: Several computational studies are being carried out to understand ligand binding modes, selectivity interactions and conformational changes during inhibitor binding. PTP inhibitors that are of current interest include quinolyl, cyclic alabenzimidazole, pyrazine, (ethynediyl)bis-benzene, pyridopyrimidine, triazolopyridine, cyclo propylphenyl phenyloxamides, oxindole and azoloarin derivatives. The development of allosteric site-directed PTP inhibitors may help in understanding the absorption and selectivity of PTP inhibitors.     

Determinants of food allergy

Food allergy is an emerging epidemic in the United States and the Western world. The determination of factors that make certain foods allergenic is still not clearly understood. Only a tiny fraction of thousands of proteins and other molecules is responsible for inducing food allergy. In this review, the authors present 3 examples of food allergies with disparate clinical presentations: peanut, soy, and mammalian meat. The potential relationships between allergen structure and function, emphasizing the importance of cross-reactive determinants, immunoglobulin E antibodies to the oligosaccharides, and the immune responses induced in humans are discussed.