Anti-CelTOS Transmission Blocking Activity in vivo and in vitro against P. falciparum by Epitope-specific Monoclonal Antibodies
Poster May 08, 2018
Shulin Xu, Alison E. Roth, Richard T. Luque, Nichole D. Salinas, Niraj H. Tolia, Samantha Barnes, Courtney Herman, John H. Adams.
Standard in vitro culture methods were used to produce mature gametocytes for the SMFA. The in vivo studies relied on an NF54 line carrying a luciferase-expressing cassette integrated in the genome. NSG mice treated with clodronate lipsome supported high-level engraftment of huRBC and can be infected by this P. falciparum luciferase reporter line, including development of mature gametocytes infectious for mosquitoes and leading to salivary gland sporozoites. This in vivo laboratory model permitted a highly sensitive transmission blocking assay to reliably quantify early oocyst development on day 22 post infection when stage V gametocytemia reached 0.07-0.18%. Mice were randomly divided into 4 groups and 60 min. before direct mosquito feed, each mouse in the antibody-treatment group received 16 mg/kg mAb in 200µl RPMI by iv injection and the blank control group received of equal volume RPMI. For the in vitro SMFA, 400 µg/ml of CelTOS mAb was added to gametocyte culture 60 min. prior to the mosquito feed. The presence of CelTOS mAb significantly inhibited oocyst development in mosquitoes in both in vivo and in vitro assays.
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of phase I (cytochrome P450s), phase II metabolizing enzymes and transporter genes in response to xenobiotics, including prescription drugs.READ MORE
Human papillomavirus (HPV) vaccine rates continue to be low in the United States. Young women ages 18-26 years are eligible for catch-up vaccination but previous research shows that relationships status and percieved risk may be barriers to HPV vaccination. The purpose of this quantitative study was to assess the association between relationship status and perceived risk for HPV among young adult women.READ MORE