Large-scale heterochromatin remodeling linked to overreplication-associated DNA damage.

Previously, we have shown that loss of the histone 3 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAX-RELATED 5 (ATXR5) and ATXR6 (ATXR6) results in the overreplication of heterochromatin. Here we show that the overreplication results in DNA damage and extensive chromocenter remodeling into unique structures we have named "overreplication-associated centers" (RACs). RACs have a highly ordered structure with an outer layer of condensed heterochromatin, an inner layer enriched in the histone variant H2AX, and a low-density core containing foci of phosphorylated H2AX (a marker of double-strand breaks) and the DNA-repair enzyme RAD51.

Open and closed: the roles of linker histones in plants and animals.

Histones package DNA in all eukaryotes and play key roles in regulating gene expression. Approximately 150 base pairs of DNA wraps around an octamer of core histones to form the nucleosome, the basic unit of chromatin. Linker histones compact chromatin further by binding to and neutralizing the charge of the DNA between nucleosomes.

Age modifies the response to recombinant human thyrotropin.

Background: A standardized protocol is used to administer recombinant human thyrotropin (rhTSH) in preparation for diagnostic studies and treatment in patients with thyroid cancer. The expectation is that serum TSH concentrations will peak on the day after the second injection and will be sufficiently elevated to stimulate uptake of radioiodine. We wished to test the hypothesis that TSH concentrations achieved after rhTSH injection are influenced by age.

Age and the thyrotropin response to hypothyroxinemia.

Context: Some studies suggest altered pituitary functioning and TSH production with aging.

Objective: Our objective was to test the hypothesis that less TSH production occurs despite comparable hypothyroxinemia with advancing age.

Design: We retrospectively studied adult outpatients of all ages with confirmed hypothyroidism and documented their TSH and free T4 concentrations.

Combination pharmacotherapy with incretins: what works best and when?

The incretin hormone glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors fill an unaddressed therapeutic gap in the treatment of type 2 diabetes mellitus (T2DM) by potentiating insulin secretion in pancreatic beta cells, suppressing glucagon secretion, delaying gastric emptying, and reducing appetite. The incretin therapies, alone or in combination with metformin and/or thiazolidinediones, yield improved glycemic control without risk of hypoglycemia and the potential for weight neutrality or even weight loss. New incretin-based approaches offer promising new strategies for treating T2DM by recruiting new, physiologically based mechanisms of action for glucoregulation in the context of a favorable safety profile.