O-GlcNAcylation and O-GlcNAc Cycling Regulate Gene Transcription: Emerging Roles in Cancer.

O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar post-translational modification (PTM) of intracellular proteins linking nutrient flux through the Hexosamine Biosynthetic Pathway (HBP) to the control of cis-regulatory elements in the genome. Aberrant O-GlcNAcylation is associated with the development, progression, and alterations in gene expression in cancer. O-GlcNAc cycling is defined as the addition and subsequent removal of the modification by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) provides a novel method for cells to regulate various aspects of gene expression, including RNA polymerase function, epigenetic dynamics, and transcription factor activity.

-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis.

The addition of a single β-d-GlcNAc sugar (-GlcNAc) by -GlcNAc-transferase (OGT) and -GlcNAc removal by -GlcNAcase (OGA) maintain homeostatic -GlcNAc levels on cellular proteins. Changes in protein -GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear. Here, we investigated the role of -GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E) addition.

Elements of fractal geometry in the H NMR spectrum of a copolymer intercalation-complex: identification of the underlying Cantor set.

Sequence-selective intercalation of pyrene into the chain-folds of a random, binary copolyimide under fast-exchange conditions results in the development of self-similar structure in the diimide region of the H NMR spectrum. The resulting spectrum can be described by the mathematics of fractals, an approach that is rationalised in terms of a dynamic summation of ring-current shielding effects produced by pyrene molecules intercalating into the chain at progressively greater distances from each "observed" diimide residue. The underlying set of all such summations is found to be a defined mathematical fractal namely the fourth-quarter Cantor set, within which the observed spectrum is embedded.

Mouse Models of Erythropoiesis and Associated Diseases.

Animal models of erythropoiesis have been, and will continue to be, important tools for understanding molecular mechanisms underlying the development of this cell lineage and the pathophysiology associated with various human erythropoietic diseases. In this regard, the mouse is probably the most valuable animal model available to investigators. The physiology and short gestational period of mice make them ideal for studying developmental processes and modeling human diseases.

Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH.

Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology.

Robust and Operationally Simple Synthesis of Poly(bis(2,2,2-trifluoroethoxy) phosphazene) with Controlled Molecular Weight, Low PDI, and High Conversion.

Synthetically straightforward conditions have been developed for the preparation of poly(bis 2,2,2-trifluoroethoxy)phosphazene with low PDI (<1.15) at high conversion (75-99%) and on a multigram scale. A combination of P NMR and GPC analyses demonstrate that molecular weight increases linearly as a function of monomer consumption, exhibiting first order kinetics with respect to monomer concentration up to high monomer conversion.