Genetic variants in the vitamin D pathway and their association with vitamin D metabolite levels: Detailed studies of an inner-city pediatric population suggest a modest but significant effect in early childhood.

Objectives: In a large cohort of healthy infants and toddlers 6-36 months of age (n = 776), we have been exploring the potential role of genetic variation in predisposition to vitamin D insufficiency. The genes encoding the key cytochrome P450 hydroxylases (CYP2R1, CYP24A1, and CYP27B1) harbour recurrent mutations of uncertain effect. This study was undertaken to look for biochemically relevant associations of these variants with inter-individual differences in vitamin D metabolism in an at-risk pediatric population.

The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma.

CD133 marks self-renewing cancer stem cells (CSCs) in a variety of solid tumors, and CD133+ tumor-initiating cells are known markers of chemo- and radio-resistance in multiple aggressive cancers, including glioblastoma (GBM), that may drive intra-tumoral heterogeneity. Here, we report three immunotherapeutic modalities based on a human anti-CD133 antibody fragment that targets a unique epitope present in glycosylated and non-glycosylated CD133 and studied their effects on targeting CD133+ cells in patient-derived models of GBM. We generated an immunoglobulin G (IgG) (RW03-IgG), a dual-antigen T cell engager (DATE), and a CD133-specific chimeric antigen receptor T cell (CAR-T): CART133.

Improving the therapeutic efficacy of mesenchymal stromal cells to restore perfusion in critical limb ischemia through pulsed focused ultrasound.

Mesenchymal stem cells (MSC) are promising therapeutics for critical limb ischemia (CLI). Mechanotransduction from pulsed focused ultrasound (pFUS) upregulates local chemoattractants to enhance homing of intravenously (IV)-infused MSC and improve outcomes. This study investigated whether pFUS exposures to skeletal muscle would improve local homing of iv-infused MSCs and their therapeutic efficacy compared to iv-infused MSCs alone.

Prognostic Importance of Atrial Fibrillation Timing and Pattern in Adults With Congestive Heart Failure: A Systematic Review and Meta-Analysis.

Background: Atrial fibrillation (AF) is common among adults with congestive heart failure (CHF). We conducted a meta-analysis to summarize the risk of mortality and cardiovascular disease associated with AF in CHF and stratified our analyses by AF timing and pattern.

Methods: We searched MEDLINE and EMBASE for observational studies examining the association of AF with cardiovascular disease and death.

Radiological-pathological correlation of diffusion tensor and magnetization transfer imaging in a closed head traumatic brain injury model.

Objective: Metrics of diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) can detect diffuse axonal injury in traumatic brain injury (TBI). The relationship between the changes in these imaging measures and the underlying pathologies is still relatively unknown. This study investigated the radiological-pathological correlation between these imaging techniques and immunohistochemistry using a closed head rat model of TBI.

Characterization of additional vitamin D binding protein variants.

The gene (GC) for the vitamin D binding protein (DBP) shows significant genetic variation. Two missense variants, p.D432E and p.

Cyclooxygenase-2 or tumor necrosis factor-α inhibitors attenuate the mechanotransductive effects of pulsed focused ultrasound to suppress mesenchymal stromal cell homing to healthy and dystrophic muscle.

Maximal homing of infused stem cells to diseased tissue is critical for regenerative medicine. Pulsed focused ultrasound (pFUS) is a clinically relevant platform to direct stem cell migration. Through mechanotransduction, pFUS establishes local gradients of cytokines, chemokines, trophic factors (CCTF) and cell adhesion molecules (CAM) in treated skeletal muscle that subsequently infused mesenchymal stromal cells (MSC) can capitalize to migrate into the parenchyma.

Post-translational regulation of CD133 by ATase1/ATase2-mediated lysine acetylation.

The CD133 cell-surface protein expresses the AC133 epitope that is associated with cancer progenitor cells and cancer resistance to traditional anticancer therapies. We report that the endoplasmic reticulum Golgi intermediate compartment residing acetyltransferases, ATase1 (NAT8B) and ATase2 (NAT8), can physically interact with CD133 to acetylate the protein on three lysine residues predicted to reside on the first extracellular loop of CD133. Site-directed mutagenesis of these residues mimicking a loss of acetylation and downregulation or inhibition of ATase1/ATase2 resulted in near-complete abolishment of CD133 protein expression.

CD133 protein N-glycosylation processing contributes to cell surface recognition of the primitive cell marker AC133 epitope.

The AC133 epitope expressed on the CD133 glycoprotein has been widely used as a cell surface marker of numerous stem cell and cancer stem cell types. It has been recently proposed that posttranslational modification and regulation of CD133 may govern cell surface AC133 recognition. Therefore, we performed a large scale pooled RNA interference (RNAi) screen to identify genes involved in cell surface AC133 expression.