PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression.

Tumor suppressor function of Gata2 in acute promyelocytic leukemia.

Most patients with acute promyelocytic leukemia (APL) can be cured with combined all-trans retinoic acid (ATRA) and arsenic trioxide therapy, which induces the destruction of PML-RARA, the initiating fusion protein for this disease. However, the underlying mechanisms by which PML-RARA initiates and maintains APL cells are still not clear. Therefore, we identified genes that are dysregulated by PML-RARA in mouse and human APL cells and prioritized GATA2 for functional studies because it is highly expressed in preleukemic cells expressing PML-RARA, its high expression persists in transformed APL cells, and spontaneous somatic mutations of GATA2 occur during APL progression in mice and humans.

Quantifying surface morphology of manufactured activated carbon and the waste coffee grounds using the Getis-Ord-Gi* statistic and Ripley's K function.

Activated carbon can be manufactured from waste coffee grounds via physical and/or chemical activation processes. However, challenges remain to quantify the differences in surface morphology between manufactured activated carbon granules and the waste coffee grounds. This paper presents a novel quantitative method to determine the quality of the physical and chemical activation processes performed in the presence of intensity inhomogeneity and identify surface characteristics of manufactured activated carbon granules and the waste coffee grounds.

Cathepsin K knockout protects against cardiac dysfunction in diabetic mice.

Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections.

Targeting Apelinergic System in Cardiometabolic Disease.

Background: Global burden of cardiometabolic disease warrants development of newer treatment strategies. Apelin is ubiquitously expressed endogenous peptide which is a ligand for the apelinergic (APJ) receptor. Apelin/APJ receptors regulate a variety of biological functions and have been implicated in cardiovascular and metabolic homeostasis.

Furostanolic saponins from Trigonella foenum-graecum alleviate diet-induced glucose intolerance and hepatic fat accumulation.

Scope: The objective of this study was to evaluate the effect of fenugreek furostanolic saponins (Fenfuro(TM) ) either alone or in combination with chlorogenic acid (GCB-70(TM) ) on insulin resistance in mice.

Methods And Results: Male C57BL/6J mice were subjected to a normal or high-fat diet (HFD) and were randomly assigned to receive Fenfuro(TM) , GCB-70(TM) , or their combination for 24 wk. Metabolic parameters, glucose tolerance, serum triglycerides, cardiac function, and hepatic insulin signaling were evaluated using indirect open-circuit calorimetry, intraperitoneal glucose tolerance test, oil red O staining, echocardiography, and Western blotting, respectively.