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Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined: during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation

Mutations in CUC1 and CUC2 (for CUP-SHAPED COTYLEDON), which are newly identified genes of Arabidopsis, caused defects in the separation of cotyledons (embryonic organs), sepals, and stamens (floral organs) as well as in the formation of shoot apical meristems. These defects were most apparent in the double mutant. Phenotypes of the mutants suggest a common mechanism for separating adjacent organs within the same whorl in both embryos and flowers. We cloned the CUC2 gene and found that the encoded protein was homologous to the petunia NO APICAL MERISTEM (NAM) protein, which is thought to act in the development of embryos and flowers

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-dependent transcription factor that has been demonstrated to regulate fat cell development and glucose homeostasis. PPAR gamma is also expressed in a subset of macrophages and negatively regulates the expression of several proinflammatory genes in response to natural and synthetic ligands. We here demonstrate that PPAR gamma is expressed in macrophage foam cells of human atherosclerotic lesions, in a pattern that is highly correlated with that of oxidation-specific epitopes. Oxidized low density lipoprotein (oxLDL) and macrophage colony-stimulating factor, which are known to be present in atherosclerotic lesions, stimulated PPAR gamma expression in primary macrophages and monocytic cell lines. PPAR gamma mRNA expression was also induced in primary macrophages and THP-1 monocytic leukemia cells by the phorbol ester 12-0-tetradecanoylphorbol 13-acetate (TPA). Inhibition of protein kinase C blocked the induction of PPAR gamma expression by TPA, but not by oxLDL, suggesting that more than one signaling pathway regulates PPAR gamma expression in macrophages. TPA induced the expression of PPAR gamma in RAW 264.7 macrophages by increasing transcription from the PPAR gamma 1 and PPAR gamma 3 promoters. In concert, these observations provide insights into the regulation of PPAR gamma expression in activated macrophages and raise the possibility that PPAR gamma ligands may influence the progression of atherosclerosis

Broadly defined, phytoestrogens include isoflavones, coumestans, and lignans. A number of these compounds have been identified in fruits, vegetables, and whole grains commonly consumed by humans. Soybeans, clover and alfalfa sprouts, and oilseeds (such as flaxseed) are the most significant dietary sources of isoflavones, coumestans, and lignans, respectively. Studies in humans, animals, and cell culture systems suggest that dietary phytoestrogens play an important role in prevention of menopausal symptoms, osteoporosis, cancer, and heart disease. Proposed mechanisms include estrogenic and antiestrogenic effects, induction of cancer cell differentiation, inhibition of tyrosine kinase and DNA topoisomerase activities, suppression of angiogenesis, and antioxidant effects. Although there currently are no dietary recommendations for individual phytoestrogens, there may be great benefit in increased consumption of plant foods

The expression of the MyoD gene homolog, nautilus (nau), in the Drosophila embryo defines a subset of mesodermal cells known as the muscle \"pioneer\" or \"founder\" cells. These cells are thought to establish the future muscle pattern in each hemisegment. Founders appear to recruit fusion-competent mesodermal cells to establish a particular muscle fiber type. In support of this concept every somatic muscle in the embryo is associated with one or more nautilus-positive cells. However, because of the lack of known (isolated) nautilus mutations, no direct test of the founder cell hypothesis has been possible. We now have utilized toxin ablation and genetic interference by double-stranded RNA (RNA interference or RNA-i) to determine both the role of the nautilus-expressing cells and the nautilus gene, respectively, in embryonic muscle formation. In the absence of nautilus-expressing cells muscle formation is severely disrupted or absent. A similar phenotype is observed with the elimination of the nautilus gene product by genetic interference upon injection of nautilus double-stranded RNA. These results define a crucial role for nautilus in embryonic muscle formation. The application of RNA interference to a variety of known Drosophila mutations as controls gave phenotypes essentially indistinguishable from the original mutation. RNA-i provides a powerful approach for the targeted disruption of a given genetic function in Drosophila

Gene regulatory networks are the most complex, extensive control systems found in nature.The interaction between biology and evolution has been the subject of great interest in recent years.The author, Eric Davidson, has been instrumental in elucidating this relationship.

The roots of plants normally carry small hairs arranged in a regular pattern. Transfer DNA-tagged lines of Arabidopsis thaliana included a mutant with few, randomly distributed root hairs. The mutated gene CAPRICE (CPC) encoded a protein with a Myb-like DNA binding domain typical of transcription factors involved in animal and plant development. Analysis in combination with other root hair mutations showed that CPC may work together with the TTG gene and upstream of the GL2 gene. Transgenic plants overexpressing CPC had more root hairs and fewer trichomes than normal. Thus, the CPC gene determines the fate of epidermal cell differentiation in Arabidopsis

The three yeast A kinase catalytic subunit isoforms are redundant for viability. We demonstrate that they have dramatically different roles in pseudohyphal development: Tpk2 is essential, whereas Tpk3 inhibits. Tpk1 has no discernible effect. Two-hybrid analysis identified the transcription factor Sfl1 as a protein that interacts specifically with Tpk2, but not Tpk1 or Tpk3. Deletion of SFL1 enhances pseudohyphal and invasive growth. Flo11, a cell surface flocculin required for pseudohyphal development, is transcriptionally regulated by Tpk2 and Sfl1. Genetic evidence indicates that Tpk2 acts upstream of Sfl1 in the regulation of Flo11.