Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia.

The hematopoietic transcription factor Ikaros () regulates normal B cell development and functions as a tumor suppressor in precursor B cell acute lymphoblastic leukemia (B-ALL). MicroRNAs (miRNAs) are small regulatory RNAs that through post-transcriptional gene regulation play critical roles in intracellular processes including cell growth in cancer. However, the role of Ikaros in the regulation of miRNA expression in developing B cells is unknown.

Deciphering the role of retinoic acid in hepatic patterning and induction in the mouse.

Retinoic acid (RA), a metabolite of vitamin A, is a small molecule and morphogen that is required for embryonic development. While normal RA signals are required for hepatic development in a variety of vertebrates, a role for RA during mammalian hepatic specification has yet to be defined. To examine the requirement for RA in murine liver induction, we performed whole embryo culture with the small molecule RA inhibitor, BMS493, to attenuate RA signaling immediately prior to hepatic induction and through liver bud formation.

Estrogen Acts Through Estrogen Receptor 2b to Regulate Hepatobiliary Fate During Vertebrate Development.

Background And Aims: During liver development, bipotent progenitor cells differentiate into hepatocytes and biliary epithelial cells to ensure a functional liver required to maintain organismal homeostasis. The developmental cues controlling the differentiation of committed progenitors into these cell types, however, are incompletely understood. Here, we discover an essential role for estrogenic regulation in vertebrate liver development to affect hepatobiliary fate decisions.

Efficient Differentiation of Human Pluripotent Stem Cells into Liver Cells.

The liver detoxifies harmful substances, secretes vital proteins, and executes key metabolic activities, thus sustaining life. Consequently, liver failure-which can be caused by chronic alcohol intake, hepatitis, acute poisoning, or other insults-is a severe condition that can culminate in bleeding, jaundice, coma, and eventually death. However, approaches to treat liver failure, as well as studies of liver function and disease, have been stymied in part by the lack of a plentiful supply of human liver cells.

Patterning of the hepato-pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud.

Unlabelled: During development, the endoderm initiates organ-restricted gene expression patterns in a spatiotemporally controlled manner. This process, termed induction, requires signals from adjacent mesodermal derivatives. Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) emanating from the cardiac mesoderm and the septum transversum mesenchyme (STM), respectively, are believed to be simultaneously and uniformly required to directly induce hepatic gene expression from the murine endoderm.

FGF signaling is required for anterior but not posterior specification of the murine liver bud.

Background: The definitive endoderm arises as a naive epithelial sheet that produces the entire gut tube and associated organs including the liver, pancreas and lungs. Murine explant studies demonstrate that fibroblast growth factor (FGF) signaling from adjacent tissues is required to induce hepatic gene expression from isolated foregut endoderm. The requirement of FGF signaling during liver development is examined by means of small molecule inhibition during whole embryo culture.

Optimizations to achieve high-level expression of cytochrome P450 proteins using Escherichia coli expression systems.

Recombinant expression of membrane-bound cytochrome P450s in bacterial expression systems provide a well-established system capable of producing large yields of catalytically active protein. As the biochemical knowledge regarding cytochrome P450s increases, so does the efficiency of protein expression through various modifications that do not disrupt the functional properties of the protein of interest. Changes such as N-terminal modifications, reduction of secondary mRNA structure, bacterial codon usage, selection of vector and host strain, as well as varying external growth conditions all appear to influence protein expression.

Functional studies of N-terminally modified CYP2J2 epoxygenase in model lipid bilayers.

CYP2J2 epoxygenase is a membrane bound cytochrome P450 that converts omega-3 and omega-6 fatty acids into physiologically active epoxides. In this work, we present a comprehensive comparison of the effects of N-terminal modifications on the properties of CYP2J2 with respect to the activity of the protein in model lipid bilayers using Nanodiscs. We demonstrate that the complete truncation of the N-terminus changes the association of this protein with the E.

Effect of a synbiotic yogurt on levels of fecal bifidobacteria, clostridia, and enterobacteria.

While ingestion of synbiotic yogurts containing Bifidobacterium animalis subsp. lactis and inulin is increasing, their effect on certain microbial groups in the human intestine is unclear. To further investigate this, a large-scale, crossover-design, placebo-controlled study was utilized to evaluate the effect of a synbiotic yogurt containing B.