Статті в журналах: "GPATs"

1

Irifune, Hidetoshi, Yu Kochi, Masayasu Hayashi, Yoshikane Kikushige, Toshihiro Miyamoto, and Koichi Akashi. "Identification of GPAT1 As a Novel Therapeutic Target for Acute Leukemia By Inhibiting Leukemia Specific Metabolism." Blood 134, Supplement_1 (November 13, 2019): 1384. http://dx.doi.org/10.1182/blood-2019-125661.

Повний текст джерела

Анотація:

With the development of mass spectrometer technology, recent studies revealed the critical roles of cancer-specific metabolism for tumor propagation in several types of cancers. In leukemia, many studies have been conducted to elucidate a leukemia-specific metabolism, and several effective treatments such as IDH1/2 inhibitors targeting acute myeloid leukemia (AML) with IDH1/2 mutation have been developed. To identify the new metabolic pathways on which acute leukemia cells depend, we purified water-soluble metabolites from CD34+ hematopoietic stem and progenitor cells (HSPCs) of healthy donors, AML and acute lymphoblastic leukemia (ALL) patients, and we comprehensively measured 116 metabolites using mass spectrometer analysis. From this experiment, we found that the cellular content of glycerol 3-phosphate (G3P) in CD34+ AML and ALL cells was lower than that of normal CD34+ HSPCs. G3P is an intermediate metabolite in the glycolysis metabolic pathway and is utilized as a substrate for phospholipids synthesis. The initial and rate-limiting step of phospholipids synthesis is the synthesis of lysophosphatidic acid (LPA) from G3P and acyl-CoA mediated by glycerol 3-phosphate acyltransferases (GPATs). Since CD34+ acute leukemia cells contained significantly lower level of G3P, we hypothesized that leukemia cells actively consumed G3P and synthesized LPA by GPATs. GPATs are classified into four isoforms based on intracellular localization and substrate preference. GPAT1 and GPAT2 are mitochondrial GPATs that are localized to the mitochondrial outer membrane, but on the other hand, GPAT3 and GPAT4 are microsomal GPATs that are localized to the endoplasmic reticulum membrane, each encoded by independent genes. GPAT1 is identified as an essential gene for the growth of leukemia cells by RNAi screen analysis in the public database (DepMap). We found that CD34+ immature AML cells exhibited higher GPAT1 expression as compared to CD34- more differentiated AML cells and normal T cells. GPAT1 knockdown inhibited the proliferation of several acute leukemia cell lines including THP-1 and Kasumi-1 in vitro and in vivo. Moreover, a mitochondrial GPATs specific inhibitor (FSG67), which was originally developed as a drug to treat obesity and diabetes, suppressed the growth of the leukemia cell lines through the induction of G1 cell cycle arrest. Growth inhibition was rescued by exogenous administration of LPA, suggesting that the synthetic activity mediated by mitochondrial GPATs should be required for acute leukemia growth. Furthermore, FSG67 induced the apoptosis of leukemia cells derived from AML and ALL patients without affecting normal CD34+ HSPCs at least in vitro. We also confirmed that the injection of FSG67 resulted in the suppression of AML and ALL propagation in vivo using patient-derived xenograft models (see figure). GPAT1 regulates the mitochondrial function by producing LPA which is an essential metabolite for maintaining mitochondrial fusion. Actually, the amount of LPA was decreased in GPAT1 knockdown acute leukemia cells. We next examined mitochondrial energy production by extracellular flux assay, and found that GPAT1 knockdown as well as FSG67 significantly suppressed oxygen consumption rate of acute leukemia cells. Consistent with the impaired mitochondrial function, FSG67 suppressed the mitochondrial membrane potential, indicating that GPAT1 should play a pivotal role in maintaining leukemia-specific mitochondrial function. These results collectively suggest that the synthesis of LPA from G3P catalyzed by GPAT1 has a critical role in propagation of acute leukemia cells irrespective of their lineage origin. Thus, GPAT1 is a novel and common therapeutic target for human acute leukemia through suppressing leukemia-specific mitochondrial function. Figure Disclosures Akashi: Celgene, Kyowa Kirin, Astellas, Shionogi, Asahi Kasei, Chugai, Bristol-Myers Squibb: Research Funding; Sumitomo Dainippon, Kyowa Kirin: Consultancy.

Стилі APA, Harvard, Vancouver, ISO та ін.

2

Cao, Jingsong, Sylvie Perez, Bryan Goodwin, Qingcong Lin, Haibing Peng, Ariful Qadri, Yingjiang Zhou, et al. "Mice deleted for GPAT3 have reduced GPAT activity in white adipose tissue and altered energy and cholesterol homeostasis in diet-induced obesity." American Journal of Physiology-Endocrinology and Metabolism 306, no. 10 (May 15, 2014): E1176—E1187. http://dx.doi.org/10.1152/ajpendo.00666.2013.

Повний текст джерела

Анотація:

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first step in the synthesis of glycerolipids and glycerophospholipids. Microsomal GPAT, the major GPAT activity, is encoded by at least two closely related genes, GPAT3 and GPAT4. To investigate the in vivo functions of GPAT3, we generated Gpat3-deficient ( Gpat3 −/−) mice. Total GPAT activity in white adipose tissue of Gpat3 −/− mice was reduced by 80%, suggesting that GPAT3 is the predominant GPAT in this tissue. In liver, GPAT3 deletion had no impact on total GPAT activity but resulted in a 30% reduction in N-ethylmaleimide-sensitive GPAT activity. The Gpat3 −/− mice were viable and fertile and exhibited no obvious metabolic abnormalities on standard laboratory chow. However, when fed a high-fat diet, female Gpat3 −/− mice showed decreased body weight gain and adiposity and increased energy expenditure. Increased energy expenditure was also observed in male Gpat3 −/− mice, although it was not accompanied by a significant change in body weight. GPAT3 deficiency lowered fed, but not fasted, glucose levels and tended to improve glucose tolerance in diet-induced obese male and female mice. On a high-fat diet, Gpat3 −/− mice had enlarged livers and displayed a dysregulation in cholesterol metabolism. These data establish GPAT3 as the primary GPAT in white adipose tissue and reveal an important role of the enzyme in regulating energy, glucose, and lipid homeostasis.

Стилі APA, Harvard, Vancouver, ISO та ін.

3

Karasawa, Ken, Kazunari Tanigawa, Ayako Harada, and Atsushi Yamashita. "Transcriptional Regulation of Acyl-CoA:Glycerol-sn-3-Phosphate Acyltransferases." International Journal of Molecular Sciences 20, no. 4 (February 22, 2019): 964. http://dx.doi.org/10.3390/ijms20040964.

Повний текст джерела

Анотація:

Acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT) is an enzyme responsible for the rate-limiting step in the synthesis of glycerophospholipids and triacylglycerol (TAG). The enzymes of mammalian species are classified into four isoforms; GPAT1 and GPAT2 are localized in the mitochondrial outer membrane, whereas GPAT3 and GPAT4 are localized in the endoplasmic reticulum membrane. The activity of each enzyme expressed is associated with physiological and pathological functions. The transcriptional regulation is well known, particularly in GPAT1. GPAT1 mRNA expression is mainly regulated by the binding of the transcriptional factor SREBP-1c to the specific element (the sterol regulatory element) flanking the GPAT1 promoter. The TAG level is controlled by the insulin-induced transcriptional expression of GPAT1, which occupies most of the GPAT activity in the liver. The transcriptional regulation of the other three GPAT isoforms remains undetermined in detail. It is predicted that retinoic acid serves as a transcription factor in the GPAT2 promoter. PPARγ (peroxisome proliferator-activated receptor γ) increases the mRNA expression of GPAT3, which is associated with TAG synthesis in adipose tissues. Although GPAT has been considered to be a key enzyme in the production of TAG, unexpected functions have recently been reported, particularly in GPAT2. It is likely that GPAT2 is associated with tumorigenesis and normal spermatogenesis. In this review, the physiological and pathophysiological roles of the four GPAT isoforms are described, alongside the transcriptional regulation of these enzymes.

Стилі APA, Harvard, Vancouver, ISO та ін.

4

Gao, Mingming, Lin Liu, Xiaowei Wang, Hoi Yin Mak, George Liu, and Hongyuan Yang. "GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy." Human Molecular Genetics 29, no. 3 (December 24, 2019): 432–43. http://dx.doi.org/10.1093/hmg/ddz300.

Повний текст джерела

Анотація:

Abstract Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs), and increased GPAT activity may be responsible for the defective adipogenesis under seipin deficiency. Here we generated Seipin−/−Gpat3−/− mice, which had mild but significant recovery of white adipose tissue mass over Seipin−/− mice. The mass of brown adipose tissue (BAT) of the Seipin−/−Gpat3−/− mice was almost completely restored to normal level. Importantly, the Seipin−/−Gpat3−/− mice showed significant improvement in liver steatosis and insulin sensitivity over Seipin−/− mice, which is attributable to the increased BAT mass and to the enhanced browning of the subcutaneous fat of the Seipin−/−Gpat3−/− mice. Together, our results establish a functional link between seipin and GPAT3 in vivo and suggest that GPAT inhibitors may have beneficial effects on BSCL2 patients.

Стилі APA, Harvard, Vancouver, ISO та ін.

5

Bratschi, Martin W., David P. Burrowes, Adam Kulaga, Jing F. Cheung, Ana L. Alvarez, Jennifer Kearley, and Vanina Zaremberg. "Glycerol-3-Phosphate Acyltransferases Gat1p and Gat2p Are Microsomal Phosphoproteins with Differential Contributions to Polarized Cell Growth." Eukaryotic Cell 8, no. 8 (June 12, 2009): 1184–96. http://dx.doi.org/10.1128/ec.00085-09.

Повний текст джерела

Анотація:

ABSTRACT Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial step in the synthesis of all glycerolipids. It is the committed and rate-limiting step and is redundant in Saccharomyces cerevisiae, mammals, and plants. GPAT controls the formation of lipid intermediates that serve not only as precursors of more-complex lipids but also as intracellular signaling molecules. Saccharomyces cerevisiae possesses two GPATs, encoded by the GAT1 and GAT2 genes. Metabolic analysis of yeast lacking either GAT1 or GAT2 indicated partitioning of the two main branches of phospholipid synthesis at the initial and rate-limiting GPAT step. We are particularly interested in identifying molecular determinants mediating lipid metabolic pathway partitioning; therefore, as a starting point, we have performed a detailed study of Gat1p and Gat2p cellular localization. We have compared Gat1p and Gat2p localization by fluorescence microscopy and subcellular fractionation using equilibrium density gradients. Our results indicate Gat1p and Gat2p overlap mostly in their localization and are in fact microsomal GPATs, localized to both perinuclear and cortical endoplasmic reticula in actively proliferating cells. A more detailed analysis suggests a differential enrichment of Gat1p and Gat2p in distinct ER fractions. Furthermore, overexpression of these enzymes in the absence of endogenous GPATs induces proliferation of distinct ER arrays, differentially affecting cortical ER morphology and polarized cell growth. In addition, our studies also uncovered a dynamic posttranslational regulation of Gat1p and Gat2p and a compensation mechanism through phosphorylation that responds to a cellular GPAT imbalance.

Стилі APA, Harvard, Vancouver, ISO та ін.

6

Bai, Yang, Yue Shen, Zhiqiang Zhang, Qianru Jia, Mengyuan Xu, Ting Zhang, Hailing Fang, et al. "A GPAT1 Mutation in Arabidopsis Enhances Plant Height but Impairs Seed Oil Biosynthesis." International Journal of Molecular Sciences 22, no. 2 (January 14, 2021): 785. http://dx.doi.org/10.3390/ijms22020785.

Повний текст джерела

Анотація:

Glycerol-3-phosphate acyltransferases (GPATs) play an important role in glycerolipid biosynthesis, and are mainly involved in oil production, flower development, and stress response. However, their roles in regulating plant height remain unreported. Here, we report that Arabidopsis GPAT1 is involved in the regulation of plant height. GUS assay and qRT-PCR analysis in Arabidopsis showed that GPAT1 is highly expressed in flowers, siliques, and seeds. A loss of function mutation in GPAT1 was shown to decrease seed yield but increase plant height through enhanced cell length. Transcriptomic and qRT-PCR data revealed that the expression levels of genes related to gibberellin (GA) biosynthesis and signaling, as well as those of cell wall organization and biogenesis, were significantly upregulated. These led to cell length elongation, and thus, an increase in plant height. Together, our data suggest that knockout of GPAT1 impairs glycerolipid metabolism in Arabidopsis, leading to reduced seed yield, but promotes the biosynthesis of GA, which ultimately enhances plant height. This study provides new evidence on the interplay between lipid and hormone metabolism in the regulation of plant height.

Стилі APA, Harvard, Vancouver, ISO та ін.

7

Mitka, Ilona, Katarzyna Ropka-Molik, and Mirosław Tyra. "Functional Analysis of Genes Involved in Glycerolipids Biosynthesis (GPAT1 and GPAT2) in Pigs." Animals 9, no. 6 (May 31, 2019): 308. http://dx.doi.org/10.3390/ani9060308.

Повний текст джерела

Анотація:

Glycerol-3-phosphate acyltransferase (GPAT) enzymes catalyze the first step in triacylglycerol (TAG) synthesis. Genes that belong to the GPAT family are potential genetic markers for intramuscular fat content (IMF) content and thus meat quality. The objective of this study was to analyze the expression of GPAT1 and GPAT2 genes in musculus longissimus lumborum, liver and subcutaneous fat of various breeds of pigs. Furthermore, correlations between the genes’ expression abundance and utility traits, meat quality and meat texture parameters of pork were determined. The results obtained showed significant differences in the mRNA level of GPAT1 between analyzed tissues and breeds. The highest expression of GPAT1 gene was observed in liver tissue (p ≤ 0.01). Furthermore, significantly higher GPAT1 transcript level in the m. longissimus lumborum was observed for duroc in comparison to other analyzed breeds (p ≤ 0.05). Expression of the GPAT2 gene was shown only in the liver tissues, however statistically significant differences between the analyzed breeds were not observed. Correlation analysis confirmed the highest association between GPAT2 gene expression level in liver and cohesiveness and resilience traits of m. longissimus lumborum (p ≤ 0.01).

Стилі APA, Harvard, Vancouver, ISO та ін.

8

Garcia-Fabiani, Maria B., Mauro A. Montanaro, Pablo Stringa, Ezequiel Lacunza, Elizabeth R. Cattaneo, Marianela Santana, Magali Pellon-Maison, and Maria R. Gonzalez-Baro. "Glycerol-3-phosphate acyltransferase 2 is essential for normal spermatogenesis." Biochemical Journal 474, no. 18 (August 31, 2017): 3093–107. http://dx.doi.org/10.1042/bcj20161018.

Повний текст джерела

Анотація:

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first and rate-limiting step in the de novo glycerolipid synthesis. The GPAT2 isoform differs from the other isoforms because its expression is restricted to male germ cells and cancer cells. It has been recently reported that GPAT2 expression in mouse testis fluctuates during sexual maturation and that it is regulated by epigenetic mechanisms in combination with vitamin A derivatives. Despite progress made in this field, information about GPAT2 role in the developing male germ cells remains unclear. The aim of the present study was to confirm the hypothesis that GPAT2 is required for the normal physiology of testes and male germ cell maturation. The gene was silenced in vivo by inoculating lentiviral particles carrying the sequence of a short-hairpin RNA targeting Gpat2 mRNA into mouse testis. Histological and gene expression analysis showed impaired spermatogenesis and arrest at the pachytene stage. Defects in reproductive fitness were also observed, and the analysis of apoptosis-related gene expression demonstrated the activation of apoptosis in Gpat2-silenced germ cells. These findings indicate that GPAT2 protein is necessary for the normal development of male gonocytes, and that its absence triggers apoptotic mechanisms, thereby decreasing the number of dividing germ cells.

Стилі APA, Harvard, Vancouver, ISO та ін.

9

LIU, Cong, Dan-Wang XIAO, Chun-Lin SHI, Xue-Fang HU, Ke-Bin WU, Chun-Yun GUAN, and Xing-Hua XIONG. "sn-glycerol-3-phosphate acyltransferases (GPATs) in plants." Hereditas (Beijing) 35, no. 12 (December 16, 2013): 1352–59. http://dx.doi.org/10.3724/sp.j.1005.2013.01352.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

10

Wendel, Angela A., Daniel E. Cooper, Olga R. Ilkayeva, Deborah M. Muoio, and Rosalind A. Coleman. "Glycerol-3-phosphate Acyltransferase (GPAT)-1, but Not GPAT4, Incorporates Newly Synthesized Fatty Acids into Triacylglycerol and Diminishes Fatty Acid Oxidation." Journal of Biological Chemistry 288, no. 38 (August 1, 2013): 27299–306. http://dx.doi.org/10.1074/jbc.m113.485219.

Повний текст джерела

Анотація:

Four glycerol-3-phosphate acyltransferase (GPAT) isoforms, each encoded by a separate gene, catalyze the initial step in glycerolipid synthesis; in liver, the major isoforms are GPAT1 and GPAT4. To determine whether each of these hepatic isoforms performs a unique function in the metabolism of fatty acid, we measured the incorporation of de novo synthesized fatty acid or exogenous fatty acid into complex lipids in primary mouse hepatocytes from control, Gpat1−/−, and Gpat4−/− mice. Although hepatocytes from each genotype incorporated a similar amount of exogenous fatty acid into triacylglycerol (TAG), only control and Gpat4−/− hepatocytes were able to incorporate de novo synthesized fatty acid into TAG. When compared with controls, Gpat1−/− hepatocytes oxidized twice as much exogenous fatty acid. To confirm these findings and to assess hepatic β-oxidation metabolites, we measured acylcarnitines in liver from mice after a 24-h fast and after a 24-h fast followed by 48 h of refeeding with a high sucrose diet to promote lipogenesis. Confirming the in vitro findings, the hepatic content of long-chain acylcarnitine in fasted Gpat1−/− mice was 3-fold higher than in controls. When compared with control and Gpat4−/− mice, after the fasting-refeeding protocol, Gpat1−/− hepatic TAG was depleted, and long-chain acylcarnitine content was 3.5-fold higher. Taken together, these data demonstrate that GPAT1, but not GPAT4, is required to incorporate de novo synthesized fatty acids into TAG and to divert them away from oxidation.

Стилі APA, Harvard, Vancouver, ISO та ін.

11

Sun, Lianping, Xiaojiao Xiang, Zhengfu Yang, Ping Yu, Xiaoxia Wen, Hong Wang, Adil Abbas, et al. "OsGPAT3 Plays a Critical Role in Anther Wall Programmed Cell Death and Pollen Development in Rice." International Journal of Molecular Sciences 19, no. 12 (December 12, 2018): 4017. http://dx.doi.org/10.3390/ijms19124017.

Повний текст джерела

Анотація:

In flowering plants, ideal male reproductive development requires the systematic coordination of various processes, in which timely differentiation and degradation of the anther wall, especially the tapetum, is essential for both pollen formation and anther dehiscence. Here, we show that OsGPAT3, a conserved glycerol-3-phosphate acyltransferase gene, plays a critical role in regulating anther wall degradation and pollen exine formation. The gpat3-2 mutant had defective synthesis of Ubisch bodies, delayed programmed cell death (PCD) of the inner three anther layers, and abnormal degradation of micropores/pollen grains, resulting in failure of pollen maturation and complete male sterility. Complementation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) experiments demonstrated that OsGPAT3 is responsible for the male sterility phenotype. Furthermore, the expression level of tapetal PCD-related and nutrient metabolism-related genes changed significantly in the gpat3-2 anthers. Based on these genetic and cytological analyses, OsGPAT3 is proposed to coordinate the differentiation and degradation of the anther wall and pollen grains in addition to regulating lipid biosynthesis. This study provides insights for understanding the function of GPATs in regulating rice male reproductive development, and also lays a theoretical basis for hybrid rice breeding.

Стилі APA, Harvard, Vancouver, ISO та ін.

12

Waschburger, Edgar, Franceli Rodrigues Kulcheski, Nicole Moreira Veto, Rogerio Margis, Marcia Margis-Pinheiro, and Andreia Carina Turchetto-Zolet. "Genome-wide analysis of the Glycerol-3-Phosphate Acyltransferase (GPAT) gene family reveals the evolution and diversification of plant GPATs." Genetics and Molecular Biology 41, no. 1 suppl 1 (March 19, 2018): 355–70. http://dx.doi.org/10.1590/1678-4685-gmb-2017-0076.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

13

Zhang, Chongben, Daniel E. Cooper, Trisha J. Grevengoed, Lei O. Li, Eric L. Klett, James M. Eaton, Thurl E. Harris, and Rosalind A. Coleman. "Glycerol-3-phosphate acyltransferase-4-deficient mice are protected from diet-induced insulin resistance by the enhanced association of mTOR and rictor." American Journal of Physiology-Endocrinology and Metabolism 307, no. 3 (August 1, 2014): E305—E315. http://dx.doi.org/10.1152/ajpendo.00034.2014.

Повний текст джерела

Анотація:

Glycerol-3-phosphate acyltransferase (GPAT) activity is highly induced in obese individuals with insulin resistance, suggesting a correlation between GPAT function, triacylglycerol accumulation, and insulin resistance. We asked whether microsomal GPAT4, an isoform regulated by insulin, might contribute to the development of hepatic insulin resistance. Compared with control mice fed a high fat diet, Gpat4 −/− mice were more glucose tolerant and were protected from insulin resistance. Overexpression of GPAT4 in mouse hepatocytes impaired insulin-suppressed gluconeogenesis and insulin-stimulated glycogen synthesis. Impaired glucose homeostasis was coupled to inhibited insulin-stimulated phosphorylation of Akt(Ser473) and Akt(Thr308). GPAT4 overexpression inhibited rictor's association with the mammalian target of rapamycin (mTOR), and mTOR complex 2 (mTORC2) activity. Compared with overexpressed GPAT3 in mouse hepatocytes, GPAT4 overexpression increased phosphatidic acid (PA), especially di16:0-PA. Conversely, in Gpat4 −/− hepatocytes, both mTOR/rictor association and mTORC2 activity increased, and the content of PA in Gpat4 −/− hepatocytes was lower than in controls, with the greatest decrease in 16:0-PA species. Compared with controls, liver and skeletal muscle from Gpat4 −/−-deficient mice fed a high-fat diet were more insulin sensitive and had a lower hepatic content of di16:0-PA. Taken together, these data demonstrate that a GPAT4-derived lipid signal, likely di16:0-PA, impairs insulin signaling in mouse liver and contributes to hepatic insulin resistance.

Стилі APA, Harvard, Vancouver, ISO та ін.

14

Quiroga, Ivana Y., Magali Pellon-Maison, Amanda L. Suchanek, Rosalind A. Coleman, and Maria R. Gonzalez-Baro. "Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and affect functionality in activated macrophages." Biochemical Journal 476, no. 1 (January 11, 2019): 85–99. http://dx.doi.org/10.1042/bcj20180381.

Повний текст джерела

Анотація:

AbstractMacrophage classical M1 activation via TLR4 triggers a variety of responses to achieve the elimination of foreign pathogens. During this process, there is also an increase in lipid droplets which contain large quantities of triacylglycerol (TAG) and phospholipid (PL). The functional consequences of this increment in lipid mass are poorly understood. Here, we studied the contribution of glycerolipid synthesis to lipid accumulation, focusing specifically on the first and rate-limiting enzyme of the pathway: glycerol-3-phosphate acyltransferase (GPAT). Using bone marrow-derived macrophages (BMDMs) treated with Kdo2-lipid A, we showed that glycerolipid synthesis is induced during macrophage activation. GPAT4 protein level and GPAT3/GPAT4 enzymatic activity increase during this process, and these two isoforms were required for the accumulation of cell TAG and PL. The phagocytic capacity of Gpat3−/− and Gpat4−/− BMDM was impaired. Additionally, inhibiting fatty acid β-oxidation reduced phagocytosis only partially, suggesting that lipid accumulation is not necessary for the energy requirements for phagocytosis. Finally, Gpat4−/− BMDM expressed and released more pro-inflammatory cytokines and chemokines after macrophage activation, suggesting a role for GPAT4 in suppressing inflammatory responses. Together, these results provide evidence that glycerolipid synthesis directed by GPAT4 is important for the attenuation of the inflammatory response in activated macrophages.

Стилі APA, Harvard, Vancouver, ISO та ін.

15

Kuhajda, Francis P., Susan Aja, Yajun Tu, Wan Fang Han, Susan M. Medghalchi, Rajaa El Meskini, Leslie E. Landree, et al. "Pharmacological glycerol-3-phosphate acyltransferase inhibition decreases food intake and adiposity and increases insulin sensitivity in diet-induced obesity." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 301, no. 1 (July 2011): R116—R130. http://dx.doi.org/10.1152/ajpregu.00147.2011.

Повний текст джерела

Анотація:

Storage of excess calories as triglycerides is central to obesity and its associated disorders. Glycerol-3-phosphate acyltransferases (GPATs) catalyze the initial step in acylglyceride syntheses, including triglyceride synthesis. We utilized a novel small-molecule GPAT inhibitor, FSG67, to investigate metabolic consequences of systemic pharmacological GPAT inhibition in lean and diet-induced obese (DIO) mice. FSG67 administered intraperitoneally decreased body weight and energy intake, without producing conditioned taste aversion. Daily FSG67 (5 mg/kg, 15.3 μmol/kg) produced gradual 12% weight loss in DIO mice beyond that due to transient 9- to 10-day hypophagia (6% weight loss in pair-fed controls). Continued FSG67 maintained the weight loss despite return to baseline energy intake. Weight was lost specifically from fat mass. Indirect calorimetry showed partial protection by FSG67 against decreased rates of oxygen consumption seen with hypophagia. Despite low respiratory exchange ratio due to a high-fat diet, FSG67-treated mice showed further decreased respiratory exchange ratio, beyond pair-fed controls, indicating enhanced fat oxidation. Chronic FSG67 increased glucose tolerance and insulin sensitivity in DIO mice. Chronic FSG67 decreased gene expression for lipogenic enzymes in white adipose tissue and liver and decreased lipid accumulation in white adipose, brown adipose, and liver tissues without signs of damage. RT-PCR showed decreased gene expression for orexigenic hypothalamic neuropeptides AgRP or NPY after acute and chronic systemic FSG67. FSG67 given intracerebroventricularly (100 and 320 nmol icv) produced 24-h weight loss and feeding suppression, indicating contributions from direct central nervous system sites of action. Together, these data point to GPAT as a new potential therapeutic target for the management of obesity and its comorbidities.

Стилі APA, Harvard, Vancouver, ISO та ін.

16

Tamada, Taro, Michael D. Feese, Stefano R. Ferri, Yoichi Kato, Rieko Yajima, Toshihiro Toguri, and Ryota Kuroki. "Substrate recognition and selectivity of plant glycerol-3-phosphate acyltransferases (GPATs) fromCucurbita moscataandSpinacea oleracea." Acta Crystallographica Section D Biological Crystallography 60, no. 1 (December 18, 2003): 13–21. http://dx.doi.org/10.1107/s0907444903020778.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

17

Morgan-Bathke, Maria, Liang Chen, Elisabeth Oberschneider, Debra Harteneck, and Michael D. Jensen. "Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity." American Journal of Physiology-Endocrinology and Metabolism 308, no. 9 (May 1, 2015): E830—E846. http://dx.doi.org/10.1152/ajpendo.00424.2014.

Повний текст джерела

Анотація:

Adipose tissue fatty acid storage varies according to sex, adipose tissue depot, and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We examined whether differences in adipose tissue glycerol-3-phosphate acyltransferase (GPAT) might play a role in these variations. We optimized an enzyme activity assay for total GPAT and GPAT1 activity in human adipose tissue and measured GPAT activity. Omental and subcutaneous adipose tissue was collected from obese and nonobese adults for measures of GPAT and GPAT1 activities, ex vivo palmitate storage, acyl-CoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT) activities, and CD36 protein. Total GPAT and GPAT1 activities decreased as a function of adipocyte size in both omental ( r = −0.71, P = 0.003) and subcutaneous ( r = −0.58, P = 0.04) fat. The relative contribution of GPAT1 to total GPAT activity increased as a function of adipocyte size, accounting for up to 60% of GPAT activity in those with the largest adipocytes. We found strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots ( r values 0.58–0.91) and between these storage factors and palmitate storage rates into TAG ( r values 0.55–0.90). We conclude that: 1) total GPAT activity decreases as a function of adipocyte size; 2) GPAT1 can account for over half of adipose GPAT activity in hypertrophic obesity; and 3) ACS, GPAT, and DGAT are coordinately regulated.

Стилі APA, Harvard, Vancouver, ISO та ін.

18

Sun, Shao-kun, Ni-na Yang, Li-jing Chen, Muhammad Irfan, Xing-hua Zhao, and Tian-lai Li. "Characterization of LpGPAT Gene inLilium pensylvanicumand Response to Cold Stress." BioMed Research International 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/792819.

Повний текст джерела

Анотація:

LpGPAT was obtained fromL. pensylvanicumusing RT-PCR and rapid amplification of cDNA ends. The cloned full-length cDNA was 1544 bp; it encoded 410 amino acids and had a molecular size of 46 KDa. The nucleic acid sequence analysis showed that it shared high homology with other known GPATs. SMAT result suggests that there is a PlsC that exists in 176-322 amino acid sequence of LpGAPT; it means LpGPAT protein is a member of the family of acyltransferase and has acyltransferase enzymatic activity. Result of real-time quantitative PCR and semiquantitative PCR support LpGPAT gene is definitely induced by low temperature stress.

Стилі APA, Harvard, Vancouver, ISO та ін.

19

Misra, Aparna, Kasim Khan, Abhishek Niranjan, Vinod Kumar, and Vidhu A. Sane. "Heterologous expression of two GPATs from Jatropha curcas alters seed oil levels in transgenic Arabidopsis thaliana." Plant Science 263 (October 2017): 79–88. http://dx.doi.org/10.1016/j.plantsci.2017.07.003.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

20

Gonzalez-Baró, Maria R., Tal M. Lewin, and Rosalind A. Coleman. "Regulation of Triglyceride Metabolism II. Function of mitochondrial GPAT1 in the regulation of triacylglycerol biosynthesis and insulin action." American Journal of Physiology-Gastrointestinal and Liver Physiology 292, no. 5 (May 2007): G1195—G1199. http://dx.doi.org/10.1152/ajpgi.00553.2006.

Повний текст джерела

Анотація:

GPAT1, one of four known glycerol-3-phosphate acyltransferase isoforms, is located on the mitochondrial outer membrane, allowing reciprocal regulation with carnitine palmitoyltransferase-1. GPAT1 is upregulated transcriptionally by insulin and SREBP-1c and downregulated acutely by AMP-activated protein kinase, consistent with a role in triacylglycerol synthesis. Knockout and overexpression studies suggest that GPAT1 is critical for the development of hepatic steatosis and that steatosis initiated by overexpression of GPAT1 causes hepatic, and perhaps also peripheral, insulin resistance. Future questions include the function of GPAT1 in relation to the other GPAT isoforms and whether the lipid intermediates synthesized by GPAT and downstream enzymes in the pathway of glycerolipid biosynthesis participate in intracellular signaling pathways.

Стилі APA, Harvard, Vancouver, ISO та ін.

21

Kuleshov, Y., P. Hettrick, D. Mackerras, M. Darveniza, and E. Jayaratne. "Occurrence of positive and negative polarity cloud-to-ground lightning flashes: case study of CGR4 and GPATS data for Brisbane, Australia." Australian Meteorological and Oceanographic Journal 61, no. 2 (June 2011): 107–12. http://dx.doi.org/10.22499/2.6102.002.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

22

Shan, Dandan, Jian-liang Li, Leeying Wu, Dongmei Li, Jonathan Hurov, James F. Tobin, Ruth E. Gimeno, and Jingsong Cao. "GPAT3 and GPAT4 are regulated by insulin-stimulated phosphorylation and play distinct roles in adipogenesis." Journal of Lipid Research 51, no. 7 (February 24, 2010): 1971–81. http://dx.doi.org/10.1194/jlr.m006304.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

23

Kang, Hyun, and Sushruta Koppula. "Houttuynia cordata Attenuates Lipid Accumulation via Activation of AMP-Activated Protein Kinase Signaling Pathway in HepG2 Cells." American Journal of Chinese Medicine 42, no. 03 (January 2014): 651–64. http://dx.doi.org/10.1142/s0192415x14500426.

Повний текст джерела

Анотація:

Houttuynia cordata (H. cordata) from the family Saururaceae is a perennial herb native to Southeast Asia. It possesses a range of medicinal properties to treat several disease symptoms including allergic inflammation and anaphylaxis. In the present investigation, we provided the molecular mechanisms underlying the role of H. cordata extract (HCE) in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes. HepG2 cells were pre-treated with various concentrations of HCE (0, 10, 20, 40, and 80 μg/mL) and treated with serum-free medium with normal glucose (5 mM) for 1 h, followed by exposure to high glucose (25 mM D-glucose) for 24 h. HCE significantly and dose-dependently attenuated lipid accumulation in human HepG2 hepatocytes when exposed to high glucose (25 mM D-glucose) (p < 0.05, p < 0.01 and p < 0.001 at 20, 40, and 80 μg/mL concentrations, respectively). Further, HCE attenuated the expression of fatty acid synthase (FAS), sterol regulatory element-binding protein-1 and glycerol 3-phosphate acyltransferases (GPATs). The adenosine monophosphate-activated protein kinase (AMPK) was also activated by HCE treatment when exposed to high glucose (25 mM D-glucose) in human HepG2 hepatocytes. This study suggests the hypolipidemic effects of HCE by the inhibition of lipid biosynthesis mediated through AMPK signaling, which may play an active role and can be developed as an anti-obesity agent.

Стилі APA, Harvard, Vancouver, ISO та ін.

24

Fernández-Santos, Rubén, Yovanny Izquierdo, Ana López, Luis Muñiz, Marta Martínez, Tomás Cascón, Mats Hamberg, and Carmen Castresana. "Protein Profiles of Lipid Droplets during the Hypersensitive Defense Response of Arabidopsis against Pseudomonas Infection." Plant and Cell Physiology 61, no. 6 (March 27, 2020): 1144–57. http://dx.doi.org/10.1093/pcp/pcaa041.

Повний текст джерела

Анотація:

Abstract Lipid droplets (LDs) have classically been viewed as seed storage particles, yet they are now emerging as dynamic organelles associated with developmental and stress responses. Nevertheless, their involvement in plant immunity has still been little studied. Here, we found LD accumulation in Arabidopsis thaliana leaves that induced a hypersensitive response (HR) after Pseudomonas infection. We established a protocol to reproducibly isolate LDs and to analyze their protein content. The expression of GFP fusion proteins in Nicotiana benthamiana and in transgenic Arabidopsis lines validated the LD localization of glycerol-3-phosphate acyltransferase 4 (GPAT4) and 8 (GPAT8), required for cutin biosynthesis. Similarly, we showed LD localization of α-dioxygenase1 (α-DOX1) and caleosin3 (CLO3), involved in the synthesis of fatty acid derivatives, and that of phytoalexin-deficient 3 (PAD3), which is involved in camalexin synthesis. We found evidence suggesting the existence of different populations of LDs, with varying protein contents and distributions. GPAT4 and GPAT8 were associated with LDs inside stomata and surrounding cells of untreated leaves, yet they were mainly confined to LDs in guard cells after bacterial inoculation. By contrast, α-DOX1 and PAD3 were associated with LDs in the epidermal cells of HR-responding leaves, with PAD3 mostly restricted to cells near dead tissue, while CLO3 had a more ubiquitous distribution. As such, the nature of the proteins identified, together with the phenotypic examination of selected mutants, suggests that LDs participate in lipid changes and in the production and transport of defense components affecting the interaction of plants with invading pathogens.

Стилі APA, Harvard, Vancouver, ISO та ін.

25

Sukumaran, Suja, Robert I. Barnes, Abhimanyu Garg, and Anil K. Agarwal. "Functional characterization of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 10/glycerol-3-phosphate acyltransferase isoform 3." Journal of Molecular Endocrinology 42, no. 6 (March 23, 2009): 469–78. http://dx.doi.org/10.1677/jme-09-0010.

Повний текст джерела

Анотація:

Synthesis of phospholipids can occur de novo or via remodeling of the existing phospholipids. Synthesis of triglycerides, a form of energy storage in cells, is an end product of these pathways. Several 1-acylglycerol-3-phosphate-O-acyltransferases (AGPATs) acylate lysophosphatidic acid (LPA) at the sn-2 (carbon 2) position to produce phosphatidic acid (PA). These enzymes are involved in phospholipids and triglyceride synthesis through an evolutionary conserved process involving serial acylations of glycerol-3-phosphate. We cloned a cDNA predicted to be an AGPAT isoform (AGPAT10). This cDNA has been recently identified as glycerol-3-phosphate-O-acyltransferase isoform 3 (GPAT3). When this AGPAT10/GPAT3 cDNA was expressed in Chinese Hamster ovary cells, the protein product localizes to the endoplasmic reticulum. In vitro enzymatic activity using lysates of human embryonic kidney-293 cells infected with recombinant AGPAT10/GPAT3 adenovirus show that the protein has a robust AGPAT activity with an apparent Vmax of 2 nmol/min per mg protein, but lacks GPAT enzymatic activity. This AGPAT has similar substrate specificities for LPA and acyl-CoA as shown for another known isoform, AGPAT2. We further show that when overexpressed in human Huh-7 cells depleted of endogenous AGPAT activity by sh-RNA-AGPAT2-lentivirus, the protein again demonstrates AGPAT activity. These observations strongly suggest that the cDNA previously identified as GPAT3 has AGPAT activity and thus we prefer to identify this clone as AGPAT10 as well.

Стилі APA, Harvard, Vancouver, ISO та ін.

26

Nampak, Haleh, Peter Love, Paul Fox-Hughes, Christopher Watson, Jagannath Aryal, and Rebecca M. B. Harris. "Characterizing Spatial and Temporal Variability of Lightning Activity Associated with Wildfire over Tasmania, Australia." Fire 4, no. 1 (March 2, 2021): 10. http://dx.doi.org/10.3390/fire4010010.

Повний текст джерела

Анотація:

Lightning strikes are pervasive, however, their distributions vary both spatially and in time, resulting in a complex pattern of lightning-ignited wildfires. Over the last decades, lightning-ignited wildfires have become an increasing threat in south-east Australia. Lightning in combination with drought conditions preceding the fire season can increase probability of sustained ignitions. In this study, we investigate spatial and seasonal patterns in cloud-to-ground lightning strikes in the island state of Tasmania using data from the Global Position and Tracking System (GPATS) for the period January 2011 to June 2019. The annual number of lightning strikes and the ratio of negative to positive lightning (78:22 overall) were considerably different from one year to the next. There was an average of 80 lightning days per year, however, 50% of lightning strikes were concentrated over just four days. Most lightning strikes were observed in the west and north of the state consistent with topography and wind patterns. We searched the whole population of lightning strikes for those most likely to cause wildfires up to 72 h before fire detection and within 10 km of the ignition point derived from in situ fire ignition records. Only 70% of lightning ignitions were matched up with lightning records. The lightning ignition efficiency per stroke/flash was also estimated, showing an annual average efficiency of 0.24% ignition per lightning stroke with a seasonal maximum during summer. The lightning ignition efficiency as a function of different fuel types also highlighted the role of buttongrass moorland (0.39%) in wildfire incidents across Tasmania. Understanding lightning climatology provides vital information about lightning characteristics that influence the probability that an individual stroke causes ignition over a particular landscape. This research provides fire agencies with valuable information to minimize the potential impacts of lightning-induced wildfires through early detection and effective response.

Стилі APA, Harvard, Vancouver, ISO та ін.

27

Lu, Li, Kun Hao, Yu Hong, Jie Liu, Jinwei Zhu, Wenjiao Jiang, Zheying Zhu, Guangji Wang, and Ying Peng. "Magnesium Isoglycyrrhizinate Reduces Hepatic Lipotoxicity through Regulating Metabolic Abnormalities." International Journal of Molecular Sciences 22, no. 11 (May 30, 2021): 5884. http://dx.doi.org/10.3390/ijms22115884.

Повний текст джерела

Анотація:

The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.

Стилі APA, Harvard, Vancouver, ISO та ін.

28

Cobo, Fernando, Jaime Borrego, Esther Gómez, Isabel Casanovas, Elizabeth Calatrava, Carla Foronda, and José María Navarro-Marí. "Clinical Findings and Antimicrobial Susceptibility of Anaerobic Bacteria Isolated in Bloodstream Infections." Antibiotics 9, no. 6 (June 19, 2020): 345. http://dx.doi.org/10.3390/antibiotics9060345.

Повний текст джерела

Анотація:

The objectives of this study were to report on the antimicrobial susceptibility of 141 clinically significant anaerobic bacteria isolated from bloodstream infections between January 2016 and April 2020 in a tertiary-care hospital in Granada (Spain) and to describe the main clinical features of the patients. Species identification was performed by MALDI-TOF MS (Bruker Daltonics, Billerica, MA, USA). Antimicrobial susceptibility tests were performed against penicillin, amoxicillin-clavulanic acid, imipenem, moxifloxacin, clindamycin, metronidazole, and piperacillin-tazobactam using the gradient diffusion technique and EUCAST breakpoints, except for moxifloxacin (CLSI breakpoints). The most frequent anaerobes were Bacteroides (43.9%, n = 62), Clostridium (24.1%, n = 34) and Gram-positive anaerobic cocci (GPACs) (15.6%, n = 22). Almost all tested anaerobes were susceptible to imipenem and amoxicillin-clavulanic acid, except for Bacteroides. High overall resistance rates to clindamycin were observed, especially for Gram-positive anaerobic cocci (GPACs) (54.5%) and for Bacteroides spp. (45.1%). Overall, low resistance rates to almost all antibiotics were observed for Clostridium. High resistance rates to penicillin were also observed for Gram-positive anaerobic bacilli (GPABs) (44.4%), as well as to metronidazole (22.2%), although only nine isolates were included. Antimicrobial susceptibility testing for anaerobes should always be performed in severe infections, such as those localized in the bloodstream. The information obtained contributes to selecting empirical treatments according with local data on resistance.

Стилі APA, Harvard, Vancouver, ISO та ін.

29

Sato, Taku J. "4G GPTAS Temptations." hamon 31, no. 1 (2021): 31. http://dx.doi.org/10.5611/hamon.31.1_31.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

30

Gidda, Satinder K., Jay M. Shockey, Steven J. Rothstein, John M. Dyer, and Robert T. Mullen. "Arabidopsis thaliana GPAT8 and GPAT9 are localized to the ER and possess distinct ER retrieval signals: Functional divergence of the dilysine ER retrieval motif in plant cells." Plant Physiology and Biochemistry 47, no. 10 (October 2009): 867–79. http://dx.doi.org/10.1016/j.plaphy.2009.05.008.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

31

Phanikumar, Bhyravajjula Ramachandra, Ammavajjala Sesha Sai Raghuram, and Ajjarapu Sriramarao. "Improving expansive clay beds with granular pile anchors (GPAs) and geogrid-encased GPAs." Proceedings of the Institution of Civil Engineers - Ground Improvement 173, no. 4 (November 2020): 237–48. http://dx.doi.org/10.1680/jgrim.18.00086.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

32

Tiba, R. "Application web-gpts version 3.0." Transfusion Clinique et Biologique 21, no. 4-5 (November 2014): 265–66. http://dx.doi.org/10.1016/j.tracli.2014.08.075.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

33

Sarkar, Jehad, La The Vinh, Young-Koo Lee, and Sungyoung Lee. "GPARS: a general-purpose activity recognition system." Applied Intelligence 35, no. 2 (March 13, 2010): 242–59. http://dx.doi.org/10.1007/s10489-010-0217-4.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

34

Santos, Amanda, Letícia Lemos Ayres da Gama Bastos, Andrezza Aparecida Aleixo, Thaís Reis Silva de Paulo, and Edmar Lacerda Mendes. "Distribuição, evolução e produção científica dos grupos de pesquisa em atividade física e saúde do Brasil." Revista Brasileira de Atividade Física & Saúde 17, no. 4 (April 28, 2016): 258–62. http://dx.doi.org/10.12820/rbafs.v.17n4p258-262.

Повний текст джерела

Анотація:

O presente estudo objetivou verificar a distribuição geográfica, evolução e produção científica dos Grupos de Pesquisa em Atividade Física e Saúde (GPAFS) no Brasil. Realizou- -se busca sistemática na base corrente e nos censos do Diretório de Grupos de Pesquisa do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), utilizando a frase exata “Atividade Física e Saúde” e Ciências da Saúde como filtro. Foram encontrados 141 GPAFS. A produção científica dos grupos foi obtida pela análise do Currículo Lattes de seus líderes. Analisaram-se os Censos a partir do ano 2000, segundo o ano de formação dos GPAFS. Divididos geograficamente, 24,82% dos GPAFS situam-se na região Sudeste, 38,30% Sul, 23,40% Nordeste, 5,67% Norte e 7,80% Centro-Oeste. Segundo a localização e a produção dos líderes, temos respectivamente, 23,02% e 32,70% no Sudeste, 34,67% e 37,10% Sul, 25,28% e 21,32% Nordeste, 6,95% e 2,36% Norte e 10,08% e 6,52% Centro-Oeste. Quanto ao período de formação, 9,93% dos GPAFS surgiram entre 2000 e 2002, 8,51% entre 2002 e 2004, 15,60% entre 2004 e 2006, 17,73% entre 2006 e 2008 e 19,86% entre 2008 e 2010. Das seis grandes áreas da saúde que estudam o tema, 72,34% dos GPAFS pertencem a Educação Física. Os dados apresentam discrepância do número de GPAFS, principalmente em relação às regiões Centro-Oeste e Norte, além da concentração da produção científica no eixo Sul-Sudeste. Políticas de incentivo à formação de jovens mestres e doutores devem ser estimuladas de forma igualitária no Brasil a fim de suprir as desigualdades entre as regiões.

Стилі APA, Harvard, Vancouver, ISO та ін.

35

Shiromoto, Yusuke, Satomi Kuramochi-Miyagawa, Ippei Nagamori, Shinichiro Chuma, Tatsuhiko Arakawa, Toru Nishimura, Hidetoshi Hasuwa, Taro Tachibana, Masahito Ikawa, and Toru Nakano. "GPAT2 is required for piRNA biogenesis, transposon silencing, and maintenance of spermatogonia in mice†." Biology of Reproduction 101, no. 1 (April 5, 2019): 248–56. http://dx.doi.org/10.1093/biolre/ioz056.

Повний текст джерела

Анотація:

Abstract PIWI-interacting RNAs (piRNAs), a subclass of germ cell-specific noncoding small RNAs, are essential for de novo DNA methylation of retrotransposon genes in embryonic testes. PIWIL2/MILI, one of three mouse PIWI family members, is indispensable for piRNA production, DNA methylation of retrotransposons presumably via piRNA, and normal spermatogenesis. In vitro analysis using germline stem cells (GS cells) revealed that glycerol-3-phosphate acyltransferase 2 (GPAT2), which is a mitochondrial outer membrane protein involved in generation of lysophosphatidic acid (LPA) and highly expressed in testes, plays important roles in spermatogenesis. Namely, GPAT2 binds to PIWIL2 and is closely involved in the biogenesis of piRNAs; this process is independent of its enzymatic activity on LPA. However, GS cells recapitulate only a limited phase of spermatogenesis and the biological functions of GPAT2 remain largely unknown. In this study, we generated GPAT2-deficient mice and conducted comprehensive analyses. The deficient mice showed defective piRNA production and subsequent de-silencing of IAP and Line-1 retrotransposons in fetal testes. In addition, apoptosis of pachytene spermatocytes was observed. These abnormalities were all common to the phenotype of PIWIL2-deficient mice, in which piRNA production was impaired. GPAT2-deficient mice exhibited apoptosis in spermatogonia at the neonatal stage, which was not observed in PIWIL2-deficient mice. These data show that GPAT2 plays a critical role in preventing apoptosis in spermatogonia.

Стилі APA, Harvard, Vancouver, ISO та ін.

36

Garcia-Fabiani, Maria B., Mauro A. Montanaro, Ezequiel Lacunza, Elizabeth R. Cattaneo, Rosalind A. Coleman, Magali Pellon-Maison, and Maria R. Gonzalez-Baro. "Methylation of the Gpat2 promoter regulates transient expression during mouse spermatogenesis." Biochemical Journal 471, no. 2 (October 2, 2015): 211–20. http://dx.doi.org/10.1042/bj20150730.

Повний текст джерела

Анотація:

We studied the expression pattern and the mechanisms governing the transcription of GPAT2, an enzyme that is highly expressed in testis. GPAT2 is regulated epigenetically and its expression correlates with the initiation of meiosis.

Стилі APA, Harvard, Vancouver, ISO та ін.

37

Collison, Lauren W., Eric J. Murphy, and Christopher A. Jolly. "Glycerol-3-phosphate acyltransferase-1 regulates murine T-lymphocyte proliferation and cytokine production." American Journal of Physiology-Cell Physiology 295, no. 6 (December 2008): C1543—C1549. http://dx.doi.org/10.1152/ajpcell.00371.2007.

Повний текст джерела

Анотація:

We have previously established a correlation between reduced mitochondrial glycerol-3-phosphate acyltransferase-1 (GPAT-1) activity and decreased proliferation in splenic T-lymphocytes from aged rats. To better understand the immunoregulatory role of GPAT-1, we examined T-lymphocyte function in young GPAT-1 knockout (KO) mice. We show that without GPAT-1, T-lymphocyte proliferation is inhibited and activation induced apoptosis is increased. Th-1 (IL-2 and IFN-γ) cytokine secretion is reduced, and Th-2 (IL-4 and IL-10) cytokine secretion is increased. These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species. Furthermore, we show increased arachidonate content and subsequent increased prostaglandin E2 secretion, which may inhibit T-lymphocyte proliferation. Taken together, we show a novel link between GPAT-1 and changes in T-lymphocyte function. These data have broad health implications because GPAT-1 suppression has recently been implicated as a new target for preventing insulin sensitivity and hepatic steatosis and we show that immune function may also be affected. Interestingly, the changes in young GPAT-1 KO splenic T-lymphocytes are similar to defects commonly seen in T-lymphocytes from aged rodents, which further underscores the significance of GPAT-1 in T-lymphocyte function.

Стилі APA, Harvard, Vancouver, ISO та ін.

38

Mitchell, J. R. D., and E. D. Saggerson. "Activities of enzymes of glycerolipid synthesis in brown adipose tissue after treatment of rats with the adrenergic agonists BRL 26830A and phenylephrine, after exposure to cold and in streptozotocin-diabetes." Biochemical Journal 277, no. 3 (August 1, 1991): 665–69. http://dx.doi.org/10.1042/bj2770665.

Повний текст джерела

Анотація:

1. Measurements were made, relative to tissue DNA, of the activities of enzymes of glycerolipid synthesis in homogenates of interscapular brown adipose tissue. These were: mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), Mg(2+)-dependent phosphatidate phosphohydrolase (PPH) and fatty acyl-CoA synthetase (FAS). 2. In normal animals, 3 days of cold-exposure (4 degrees C) increased all activities. The increase in mitochondrial GPAT activity was particularly pronounced (5-fold). Administration of the beta-adrenergic agonist BRL 26830A mimicked the effect of cold on microsomal GPAT activity. Mitochondrial GPAT, PPH and FAS activities were unresponsive to BRL 26830A. The alpha-adrenergic agonist phenylephrine significantly decreased activities of GPAT and PPH. 3. Streptozotocin-diabetes decreased mitochondrial GPAT activity, but did not abolish the effect of cold to increase this activity or the activity of microsomal GPAT. Diabetes abolished the effect of cold on PPH and FAS activities. 4. The findings are relevant to signals that drive early events in mitochondriogenesis and cell proliferation in brown adipose tissue on exposure to cold.

Стилі APA, Harvard, Vancouver, ISO та ін.

39

Bakir, Saad T., and Bob McNeal. "Monitoring The Level Of Students GPA's Over Time." American Journal of Business Education (AJBE) 3, no. 6 (June 1, 2010): 43–50. http://dx.doi.org/10.19030/ajbe.v3i6.441.

Повний текст джерела

Анотація:

A nonparametric (or distribution-free) statistical quality control chart is used to monitor the cumulative grade point averages (GPAs) of students over time. The chart is designed to detect any statistically significant positive or negative shifts in student GPAs from a desired target level. This nonparametric control chart is based on the signed-ranks of the GPAs of the sampled students. The exact false alarm rate and the in-control average run length of the proposed chart can be computed exactly and are independent of the underlying probability distribution of GPAs. The traditional Shewhart X-bar control chart for monitoring the mean of a process is based on the assumption that data follows a normal distribution. However, student GPAs may differ significantly from the normal distribution. As a result, using a traditional control chart to monitor the GPAs of students may lead to incorrectly specifying the control limits and the average run length and/or the false alarm rate of the chart. A test study was conducted at the College of Business Administration at Alabama State University. The study monitored the median cumulative GPAs of management majors during the period Spring 2005 through Spring 2009. The study revealed that the GPAs of students were stable at a median level of 2.6 over the period of the study.

Стилі APA, Harvard, Vancouver, ISO та ін.

40

Zhu, Xiphias Ge, Shirony Nicholson Puthenveedu, Yihui Shen, Konnor La, Can Ozlu, Tim Wang, Diana Klompstra, et al. "CHP1 Regulates Compartmentalized Glycerolipid Synthesis by Activating GPAT4." Molecular Cell 74, no. 1 (April 2019): 45–58. http://dx.doi.org/10.1016/j.molcel.2019.01.037.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

41

Lee, Misu, Amelie Lupp, Nigel Mendoza, Niamh Martin, Rudi Beschorner, Jürgen Honegger, Jürgen Schlegel, et al. "SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary." Endocrine-Related Cancer 22, no. 1 (December 16, 2014): 111–19. http://dx.doi.org/10.1530/erc-14-0472.

Повний текст джерела

Анотація:

Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients. The somatostatin analogs (SSAs) octreotide and lanreotide that preferentially target somatostatin receptor type 2 (SSTR2) have little effect on GPAs. It is widely accepted that the expression of specific SSTR subtypes determines the response to SSAs. Given that previous studies on mRNA and protein expression of SSTRs in GPAs have generated conflicting results, we investigated the expression of SSTR2, SSTR3, and SSTR5 (the main targets of available SSAs) in a clinically and pathologically well-characterized cohort of 108 patients with GPAs. A total of 118 samples were examined by immunohistochemistry using validated and specific MABs. Matched primary and recurrent tissues were available for ten patients. The results obtained were validated in an independent cohort of 27 GPAs. We observed that SSTR3 was significantly more abundant than SSTR2 (P<0.0001) in GPAs, while full-length SSTR5 was only expressed in few tumors. Expression of SSTR3 was similar in primary and recurrent adenomas, was high in potentially aggressive lesions, and did not change significantly in adenomas that recurred after irradiation. In conclusion, low levels of expression of SSTR2 may account for the limited response of GPAs to octreotide and lanreotide. Given the potent anti-proliferative, pro-apoptotic, and anti-angiogenic activities of SSTR3, targeting this receptor with a multireceptor ligand SSA such as pasireotide may be indicated for potentially aggressive GPAs.

Стилі APA, Harvard, Vancouver, ISO та ін.

42

MISHRA, Sanjay, and Yasushi KAMISAKA. "Purification and characterization of thiol-reagent-sensitive glycerol-3-phosphate acyltransferase from the membrane fraction of an oleaginous fungus." Biochemical Journal 355, no. 2 (April 6, 2001): 315–22. http://dx.doi.org/10.1042/bj3550315.

Повний текст джерела

Анотація:

Glycerol-3-phosphate acyltransferase (GPAT), responsible for the first committed, rate-limiting, step of glycerolipid synthesis, was purified to homogeneity from the membrane fraction of an oleaginous fungus, Mortierella ramanniana var. angulispora. The enzyme was solubilized from the membrane fraction by pretreatment with 0.05% Triton X-100 and treatment of the resulting pellet with 0.3% Triton X-100. The enzyme was subsequently purified by column chromatography on heparin-Sepharose, Yellow 86 agarose, a second heparin-Sepharose column, Superdex-200 and hydroxylapatite Bio-Gel. Enzyme activity was finally enriched 1308-fold over that of the starting membrane fraction. SDS/PAGE of the purified fraction revealed a single band with a molecular mass of 45kDa. Native PAGE showed a major band that corresponded to GPAT activity. Enzyme activity was inhibited by thiol reagents, suggesting that it originated from microsomes rather than mitochondria. Purified GPAT depended on exogenous oleoyl-CoA and sn-glycerol-3-phosphate, with the highest activity at approx. 50 and 250µM, respectively, and preferred oleoyl-CoA 5.4-fold over palmitoyl-CoA as an acyl donor. Anionic phospholipids, such as phosphatidic acid and phosphatidylserine, were absolutely required for activity of the purified enzyme, and their ability to activate GPAT was influenced by the purity of the GPAT preparation. Bivalent cations, such as Mg2+ and Ca2+, inhibited purified GPAT activity, whereas 5mM Mn2+ elevated activity approx. 2-fold. These results provide new insights into the molecular characterization of microsomal GPAT, which has not been well characterized compared with mitochondrial and plastidic GPAT.

Стилі APA, Harvard, Vancouver, ISO та ін.

43

Montali, Aurora, Francesca Berini, Maurizio Francesco Brivio, Maristella Mastore, Alessio Saviane, Silvia Cappellozza, Flavia Marinelli, and Gianluca Tettamanti. "A Silkworm Infection Model for In Vivo Study of Glycopeptide Antibiotics." Antibiotics 9, no. 6 (June 4, 2020): 300. http://dx.doi.org/10.3390/antibiotics9060300.

Повний текст джерела

Анотація:

Glycopeptide antibiotics (GPAs) are drugs of last resort for treating infections by Gram-positive bacteria. They inhibit bacterial cell wall assembly by binding to the d-Ala-d-Ala terminus of peptidoglycan precursors, leading to cell lysis. Vancomycin and teicoplanin are first generation GPAs, while dalbavancin is one of the few, recently approved, second generation GPAs. In this paper, we developed an in vivo insect model to compare, for the first time, the efficacy of these three GPAs in curing Staphylococcus aureus infection. Differently from previous reports, Bombyx mori larvae were reared at 37 °C, and the course of infection was monitored, following not only larval survival, but also bacterial load in the insect body, hemocyte activity, phenoloxidase activity, and antimicrobial peptide expression. We demonstrated that the injection of S. aureus into the hemolymph of B. mori larvae led to a marked reduction of their survival rate within 24–48 h. GPAs were not toxic to the larvae and cured S. aureus infection. Dalbavancin was more effective than first generation GPAs. Due to its great advantages (i.e., easy and safe handling, low rearing costs, low antibiotic amount needed for the tests, no restrictions imposed by ethical and regulatory issues), this silkworm infection model could be introduced in preclinical phases—prior to the use of mice—accelerating the discovery/development rate of novel GPAs.

Стилі APA, Harvard, Vancouver, ISO та ін.

44

Verspohl, E. J., H. P. Ammon, and M. Klosa. "Anti-insulin antiserum increases inositol phosphate accumulation in rat pancreatic islets." Biochemical Journal 267, no. 2 (April 15, 1990): 339–42. http://dx.doi.org/10.1042/bj2670339.

Повний текст джерела

Анотація:

The role of insulin in modulating phosphoinositide breakdown and accumulation of inositol phosphates was investigated in isolated rat pancreatic islets by using GPAIS (guinea-pig anti-insulin antiserum) that neutralizes effects of insulin in the medium. At either 3.0 mM- or 16.7 mM-glucose or 3.0 mM-glucose plus 10 microM-arecaidine propargyl ester (muscarinic receptor agonist), GPAIS (but not control serum) was able to increase InsP2 and InsP3, but not InsP, in myo-[3H] inositol-prelabelled islets. The effect of GPAIS on 3H incorporation into InsP3 was dose-dependent, with a half-maximal effect at a concentration able to bind 4004 +/- 163 microunits of insulin. A specific mass assay of the biologically relevant isomer Ins (1,4,5)P3 revealed a huge increase (greater than 3-folf). Formation of PtdIns, PtdInsP and PtdInsP2 was not affected by GPAIS. This is indirect evidence for an effect of insulin on inositide metabolism, and therefore endogenously released insulin may have led to an underestimation in earlier studies of effects of insulinotropic substances on inositol phosphate accumulation.

Стилі APA, Harvard, Vancouver, ISO та ін.

45

SAFDER, Imran, Gaoneng SHAO, Zhonghua SHENG, Peisong HU, and Shaoqing TANG. "Identification of SNPs in rice GPAT genes and in silico analysis of their functional impact on GPAT proteins." Notulae Botanicae Horti Agrobotanici Cluj-Napoca 49, no. 3 (September 27, 2021): 12346. http://dx.doi.org/10.15835/nbha49312346.

Повний текст джерела

Анотація:

SNPs are the most common nucleotide variations in the genome. Functional SNPs in the coding region, known as nonsynonymous SNPs (nsSNPs), change amino acid residues and affect protein function. Identifying functional SNPs is an uphill task as it is difficult to correlate between variation and phenotypes in association studies. Computational in silico analysis provides an opportunity to understand the SNPs functional impact to proteins and facilitate experimental approaches in understanding the relationship between the phenotype and genotype. Advancement in sequencing technologies contributed to sequencing thousands of genomes. As a result, many public databases have been designed incorporating this sequenced data to explore nucleotide variations. In this study, we explored functional SNPs in the rice GPAT family (as a model plant gene family), using 3000 Rice Genome Sequencing Project data. We identified 1056 SNPs, among hundred rice varieties in 26 GPAT genes, and filtered 98 nsSNPs. We further investigated the structural and functional impact of these nsSNPs using various computational tools and shortlisted 13 SNPs having high damaging effects on protein structure. We found that rice GPAT genes can be influenced by nsSNPs and they might have a major effect on regulation and function of GPAT genes. This information will be useful to understand the possible relationships between genetic mutation and phenotypic variation, and their functional implication on rice GPAT proteins. The study will also provide a computational pathway to identify SNPs in other rice gene families.

Стилі APA, Harvard, Vancouver, ISO та ін.

46

Hannouf, M. B., E. Winquist, S. M. Mahmud, M. Brackstone, S. Sarma, G. Rodrigues, P. K. Rogan, J. S. Hoch, and G. S. Zaric. "The clinical significance of occult gynecologic primary tumours in metastatic cancer." Current Oncology 24, no. 5 (October 30, 2017): 368. http://dx.doi.org/10.3747/co.24.3594.

Повний текст джерела

Анотація:

Objective We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os).Methods We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002−2011. We defined patients as having an “occult” primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have “obvious” primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt.Results Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women (n = 285 of 2552, 11.2%) than in men (n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours (n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts (n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses.Conclusions In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes.

Стилі APA, Harvard, Vancouver, ISO та ін.

47

Martens, Fred L. "Selection of Physical Education Students and Success in Student Teaching." Journal of Teaching in Physical Education 6, no. 4 (July 1987): 411–24. http://dx.doi.org/10.1123/jtpe.6.4.411.

Повний текст джерела

Анотація:

This is an extension of a 1977 study on the effectiveness, in terms of success in student teaching, of a process for screening students for a physical education teacher preparation program. Preentry data including interview ratings, secondary school GPAs, and skill and fitness scores, as well as postentry data including university GPAs, were correlated with student teaching ratings (STRs) on a total of402 graduates between 1967 and 1983 at the University of Victoria. In the 1986 study, in addition to the correlations, ANOVAs were computed. The correlation matrix revealed significant but low positive correlations between secondary GPAs and university GPAs generally, and between STR and 3rd-, 4th-, and 5th-year GPA, respectively. ANOVAs revealed no significant differences in achieved STRs between interview categories, teaching attitude categories, or the four levels of entering GPAs. The only predictive power of preentry data was exhibited by entering GPA in presaging academic attainment in the 5-year program. In general, no preentry data were helpful in predicting teaching success.

Стилі APA, Harvard, Vancouver, ISO та ін.

48

Ibanez, Vincent, John R. Slate, and Cheryl Kelsey. "Computer Gaming and Student Achievement: Investigating Middle School Students’ Behaviors." Journal of Youth Development 3, no. 3 (December 1, 2008): 177–84. http://dx.doi.org/10.5195/jyd.2008.297.

Повний текст джерела

Анотація:

In spite of very little research on the subject, a growing concern exists among professionals that excessive time spent by students on computer gaming may have an undesirable effect in scholastic achievement. In this study, middle grade students self-reported their time spent on computer gaming for a one week time period. These self-reports were related with their GPAs at the end of the semester. Analysis of 114 students’ GPAs in English, Math, and Science indicated the presence of a statistically significant difference in English GPAs between students in the High Computer Gaming group from students in the Moderate and Low Computer Gaming groups. No differences were yielded for Math or Science GPAs. Implications are discussed.

Стилі APA, Harvard, Vancouver, ISO та ін.

49

Loritz, Donald. "GENERALIZED TRANSITION NETWORK PARSING FOR LANGUAGE STUDY." CALICO Journal 10, no. 1 (January 14, 2013): 5–22. http://dx.doi.org/10.1558/cj.v10i1.5-22.

Повний текст джерела

Анотація:

GPARS is a generalized transition network system designed for language study by bothstudents and researchers. The GPARS system generalizes the Augmented TransitionNetwork formalism by allowing top-down, bottom-up, depth-first, breadth-first,deterministic, and nondeterministic parsing strategies to be freely intermixed. Thesevarious strategies have also allowed the system to be used for par-sing Chinese,Russian, Japanese, and other languages.

Стилі APA, Harvard, Vancouver, ISO та ін.

50

Hughey, Aaron W. "Observed Differences in Graduate Record Examination Scores and Mean Undergraduate Grade Point Averages by Gender and Race among Students Admitted to a Master's Degree Program in College Student Affairs." Psychological Reports 77, no. 3_suppl (December 1995): 1315–21. http://dx.doi.org/10.2466/pr0.1995.77.3f.1315.

Повний текст джерела

Анотація:

Graduate Record Examination scores and undergraduate grade point averages (GPAs) were examined for 218 students admitted to a master's degree program in college student affairs from August 1985 through May 1995. Analysis of variance yielded no statistically significant differences between men and women on Graduate Record Examination scores, although a significant difference was observed when undergraduate GPAs were examined. There was also a statistically significant difference between African-American and Caucasian students for both Graduate Record Examination scores and undergraduate GPAs. Pearson product-moment correlations between scores on the Graduate Record Examination and undergraduate GPAs were consistently low. These findings support the notion that use of the Graduate Record Examination as an admissions criterion for college student affairs graduate programs warrants further scrutiny.

Стилі APA, Harvard, Vancouver, ISO та ін.

Статті в журналах з теми "GPATs"

Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями