Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern

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Petit, Nathalie; Lescure, Alain; Rederstorff, Mathieu

2003-01-01

Rigid spine muscular dystrophy and the classical form of multiminicore disease are caused by mutations in SEPN1 gene, leading to a new clinical entity referred to as SEPN1-related myopathy. SEPN1 codes for selenoprotein N, a new member of the selenoprotein family, the function of which is still u...

Selenium, selenoproteins and the thyroid gland: interactions in health and disease.

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Schomburg, Lutz

2011-10-18

The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, enzymes involved in thyroid hormone metabolism, regulation of redox state and protection from oxidative damage. Selenium content in selenium-sensitive tissues such as the liver, kidney or muscle and expression of nonessential selenoproteins, such as the glutathione peroxidases GPx1 and GPx3, is controlled by nutritional supply. The thyroid gland is, however, largely independent from dietary selenium intake and thyroid selenoproteins are preferentially expressed. As a consequence, no explicit effects on thyroid hormone profiles are observed in healthy individuals undergoing selenium supplementation. However, low selenium status correlates with risk of goiter and multiple nodules in European women. Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined. The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenium supplementation, which might primarily disrupt self-amplifying cycles of the endocrine-immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens. Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction.

Selenoprotein P in colitis-associated carcinoma

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Short, Sarah P.; Whitten-Barrett, Caitlyn; Williams, Christopher S.

2016-01-01

ABSTRACT Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine. PMID:27314080

Selenium Deficiency Influences the mRNA Expression of Selenoproteins and Cytokines in Chicken Erythrocytes.

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Luan, Yilin; Zhao, Jinxin; Yao, Haidong; Zhao, Xia; Fan, Ruifeng; Zhao, Wenchao; Zhang, Ziwei; Xu, Shiwen

2016-06-01

Selenium (Se) deficiency induces hemolysis in chickens, but the molecular mechanism for this effect remains unclear. Se primarily elicits its function through the activity of selenoproteins, which contain the unique amino acid selenocysteine (Sec). In this study, we aimed to investigate the effect of Se deficiency on the expression of 24 selenoproteins and 10 cytokines. One hundred eighty chickens were randomly divided into 2 groups (90 chickens per group). During the entire experimental period, chickens were allowed ad libitum consumption of feed and water. The chickens were fed either a Se-deficient diet (0.008 mg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or a Se-supplemented diet (as sodium selenite) at 0.2 mg/kg for 35 days. At the 35th day, the messenger RNA (mRNA) levels of 24 selenoproteins and 10 cytokines were examined in erythrocytes of 5 chickens per group, and the correlation was analyzed. The results showed that the expression of 24 selenoproteins and 7 cytokines (IL-2, IL-4, IL-8, IL-10, IL-12β, TGF-β4, and IFN-γ) decreased (P chicken erythrocytes (P chickens was damaged by the Se deficiency. Correlation analysis suggested that although the expression of 24 selenoproteins and 7 cytokines decreased and that of 3 cytokines increased, there was a close correlation between their expression levels and a Se diet. These results suggested that Se deficiency influenced the expressions of 24 selenoproteins and 10 cytokines in chicken erythrocytes, revealing a relationship between Se and the chicken immune system. This study offers information regarding the mechanism of Se deficiency-induced hemolysis.

Complete Genome Sequence of the Methanococcus maripaludis Type Strain JJ (DSM 2067), a Model for Selenoprotein Synthesis in Archaea.

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Poehlein, Anja; Heym, Daniel; Quitzke, Vivien; Fersch, Julia; Daniel, Rolf; Rother, Michael

2018-04-05

Methanococcus maripaludis type strain JJ (DSM 2067) is an important organism because it serves as a model for primary energy metabolism and hydrogenotrophic methanogenesis and is amenable to genetic manipulation. The complete genome (1.7 Mb) harbors 1,815 predicted protein-encoding genes, including 9 encoding selenoproteins. Copyright © 2018 Poehlein et al.

Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif

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Shchedrina, Valentina A.; Novoselov, Sergey V.; Malinouski, Mikalai Yu.; Gladyshev, Vadim N.

2007-01-01

Selenocysteine (Sec, U) insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element. Selenoproteins with known functions are oxidoreductases containing a single redox-active Sec in their active sites. In this work, we identified a family of selenoproteins, designated SelL, containing two Sec separated by two other residues to form a UxxU motif. SelL proteins show an unusual occur...

Galectin-1 Is an Interactive Protein of Selenoprotein M in the Brain

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Qiong Liu

2013-11-01

Full Text Available Selenium, an essential trace element for human health, mainly exerts its biological function through selenoproteins. Selenoprotein M (SelM is one of the highly expressed selenoproteins in the brain, but its biological effect and molecular mechanism remain unclear. Thus, the interactive protein of SelM was investigated in this paper to guide further study. In order to avoid protein translational stop, the selenocysteine-encoding UGA inside the open reading frame of SelM was site-directly changed to the cysteine-encoding UGC to generate the SelM' mutant. Meanwhile, its N terminal transmembrane signal peptide was also cut off. This truncated SelM' was used to screen a human fetal brain cDNA library by the yeast two-hybrid system. A new interactive protein of SelM' was found to be galectin-1 (Gal-1. This protein-protein interaction was further verified by the results of fluorescence resonance energy transfer techniques, glutathione S-transferase pull-down and co-immunoprecipitation assays. As Gal-1 plays important roles in preventing neurodegeneration and promoting neuroprotection in the brain, the interaction between SelM' and Gal-1 displays a new direction for studying the biological function of SelM in the human brain.

Structure- and cell-specific effects of imidoselenocarbamates on selenoprotein expression and activity in liver cells in culture.

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Ibáñez, Elena; Stoedter, Mette; Hofmann, Peter Josef; Plano, Daniel; Calvo, Alfonso; Nguewa, Paul A; Palop, Juan Antonio; Sanmartín, Carmen; Schomburg, Lutz

2012-12-01

The essential micronutrient selenium (Se) exerts its biological effects mainly through selenoproteins thereby affecting a number of physiological pathways including intracellular redox control, stress response and cancer cell proliferation. Besides affecting selenoprotein expression, some selenocompounds have been synthesized and analyzed in order to serve as chemotherapeutic substances preferentially targeting cancer cells. This promising chemotherapeutic potential has recently been verified for a particular imidoselenocarbamate in a mouse tumor model. In the present study we tested the effects of this and a number of related Se-methyl- and Se-benzyl-imidoselenocarbamates on selenoprotein expression in nontransformed and hepatic carcinoma cells in culture. Most of the Se-benzyl-imidoselenocarbamates strongly stimulated selenoprotein P (SePP) secretion while the Se-methyl-imidoselenocarbamates elicited less pronounced effects in hepatocarcinoma HepG2 cells. However, most of the Se-methyl-imidoselenocarbamates increased glutathione peroxidase (GPx) activity and decreased thioredoxin reductase (TXNRD) activity in parallel, while the majority of the Se-benzyl-imidoselenocarbamates were without a respective effect in HepG2 cells. Performing inhibitor assays in vitro, GPx activity was unaffected by the imidoselenocarbamates. In contrast, most of the Se-methyl-imidoselenocarbamates inhibited TXNRD activity in vitro in line with the results in HepG2 cells. Both classes of imidoselenocarbamates strongly induced selenoprotein S (SELS) expression without a respective increase in ER stress or unfolded protein response which are known inducers of SELS biosynthesis. Notably, many of these effects were cancer cell-specific, and not observed in nontransformed AML12 hepatocytes. Our results indicate that these novel selenocompounds affect expression and activity of crucial selenoenzymes in a compound- and cell-specific way in hepatocytes. Especially the Se

Selenium Pretreatment Alleviated LPS-Induced Immunological Stress Via Upregulation of Several Selenoprotein Encoding Genes in Murine RAW264.7 Cells.

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Wang, Longqiong; Jing, Jinzhong; Yan, Hui; Tang, Jiayong; Jia, Gang; Liu, Guangmang; Chen, Xiaoling; Tian, Gang; Cai, Jingyi; Shang, Haiying; Zhao, Hua

2018-04-18

This study was conducted to profile selenoprotein encoding genes in mouse RAW264.7 cells upon lipopolysaccharide (LPS) challenge and integrate their roles into immunological regulation in response to selenium (Se) pretreatment. LPS was used to develop immunological stress in macrophages. Cells were pretreated with different levels of Se (0, 0.5, 1.0, 1.5, 2.0 μmol Se/L) for 2 h, followed by LPS (100 ng/mL) stimulation for another 3 h. The mRNA expression of 24 selenoprotein encoding genes and 9 inflammation-related genes were investigated. The results showed that LPS (100 ng/mL) effectively induced immunological stress in RAW264.7 cells with induced inflammation cytokines, IL-6 and TNF-α, mRNA expression, and cellular secretion. LPS increased (P immunological stress in RAW264.7 cells accompanied with the global downregulation of selenoprotein encoding genes and Se pretreatment alleviated immunological stress via upregulation of a subset of selenoprotein encoding genes.

Studies on selenoproteins in bovine kidneys by gel chromatography and neutron activation

Energy Technology Data Exchange (ETDEWEB)

Chatt, A.; Jayawickreme, C.K.

1986-01-01

Selenium at low concentrations has been claimed to be an element which is essential for life and growth. In recent years, selenium attracted increasing interest from researchers around the world because of its possible biological functions in preventing cancer, enhancing the immune system, slowing the aging process, and stimulating sexual activity. In living matter, selenium is mainly incorporated with macromolecules. Much of the metabolic behavior, biological effects, and involvement in homeostatic mechanism of this element may very well depend on the presence of the particular type of selenoproteins in the system. Neutron activation analysis (NAA) in conjunction with several bioanalytical techniques can be used to characterize metalloproteins in general. In a recent study, the distribution of trace elements in subcellular fractions of bovine kidney has been reported. The present work deals with the application of NAA together with other techniques to the isolation and characterization of selenoproteins in bovine kidneys with particular emphasis on the NAA method developed.

Studies on selenoproteins in bovine kidneys by gel chromatography and neutron activation

International Nuclear Information System (INIS)

Chatt, A.; Jayawickreme, C.K.

1986-01-01

Selenium at low concentrations has been claimed to be an element which is essential for life and growth. In recent years, selenium attracted increasing interest from researchers around the world because of its possible biological functions in preventing cancer, enhancing the immune system, slowing the aging process, and stimulating sexual activity. In living matter, selenium is mainly incorporated with macromolecules. Much of the metabolic behavior, biological effects, and involvement in homeostatic mechanism of this element may very well depend on the presence of the particular type of selenoproteins in the system. Neutron activation analysis (NAA) in conjunction with several bioanalytical techniques can be used to characterize metalloproteins in general. In a recent study, the distribution of trace elements in subcellular fractions of bovine kidney has been reported. The present work deals with the application of NAA together with other techniques to the isolation and characterization of selenoproteins in bovine kidneys with particular emphasis on the NAA method developed

Podocyte specific knock out of selenoproteins does not enhance nephropathy in streptozotocin diabetic C57BL/6 mice

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Carlson Bradley A

2008-07-01

Full Text Available Abstract Background Selenoproteins contain selenocysteine (Sec, commonly considered the 21st genetically encoded amino acid. Many selenoproteins, such as the glutathione peroxidases and thioredoxin reductases, protect cells against oxidative stress by functioning as antioxidants and/or through their roles in the maintenance of intracellular redox balance. Since oxidative stress has been implicated in the pathogenesis of diabetic nephropathy, we hypothesized that selenoproteins protect against this complication of diabetes. Methods C57BL/6 mice that have a podocyte-specific inability to incorporate Sec into proteins (denoted in this paper as PodoTrsp-/- and control mice were made diabetic by intraperitoneal injection of streptozotocin, or were injected with vehicle. Blood glucose, body weight, microalbuminuria, glomerular mesangial matrix expansion, and immunohistochemical markers of oxidative stress were assessed. Results After 3 and 6 months of diabetes, control and PodoTrsp-/- mice had similar levels of blood glucose. There were no differences in urinary albumin/creatinine ratios. Periodic acid-Schiff staining to examine mesangial matrix expansion also demonstrated no difference between control and PodoTrsp-/- mice after 6 months of diabetes, and there were no differences in immunohistochemical stainings for nitrotyrosine or NAD(PH dehydrogenase, quinone 1. Conclusion Loss of podocyte selenoproteins in streptozotocin diabetic C57BL/6 mice does not lead to increased oxidative stress as assessed by nitrotyrosine and NAD(PH dehydrogenase, quinone 1 immunostaining, nor does it lead to worsening nephropathy.

Maternal reproductive health: Expression patterns of antioxidant enzyme selenoproteins of post-implantation embryos conceived by ethanol-treated murine mothers supplemented with α-tocopherol

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Gliceria B Ramos

2017-01-01

Full Text Available Objective: To investigate if the protective effect of α-tocopherol against the impact of ethanol on brain morphogenesis involved the activity of the selenoproteins phospholipid hydroperoxide glutathione peroxidase (PHGPx; GPx4 and selenoprotein P (SelPP that have roles against oxidative stress.Methods: Forty female mice were randomly assigned into natural control (CON, positive control (ETOH, low-, medium-, and high-α-tocopherol-supplemented-ethanol groups (LTOC, MTOC, HTOC, respectively. CON received drinking water without ethanol while ETOH, LTOC, MTOC and HTOC groups received 20% ethanol in drinking water. The supplemented groups were given respective dosages of α-tocopherol, 0.410, 0.819, and 1.640 mg/g body weight, at day 14 before mating onwards to the day 9 of gestation. At 10.5 ED of gestation (1 100 h, the pregnant females were sacrificed by cervical dislocation and the embryos were harvested. Total RNA were extracted, cDNA synthesis and qRT-PCR analyses were carried out.Results: The level of expression of PHGPx in the positive control was significantly lower than that of the natural control. Among the three α-tocopherol-supplemented groups, only the medium dose-group was significantly higher than the positive control. The level of expression of SelPP in the positive control was significantly lower than those of the natural control, the low- and medium-dose-tocopherol supplemented groups. In the high dose-α-tocopherol supplemented group, the level of expression was not significantly different from the positive control but significantly lower than the natural control.Conclusions: The activity of the selenoproteins PHGPx and SelPP are involved in the internetwork of antioxidative enzymes with vitamin E when given up to a medium dose only and is one of the possible pathways of shielding embryonic development against the impact of ethanol on brain morphogenesis. This study strengthens the impact of dietary α-tocopherol and Selenium

Maternal reproductive health: Expression patterns of antioxidant enzyme selenoproteins of post-implantation embryos conceived by ethanol-treated murine mothers supplemented with α-tocopherol

Directory of Open Access Journals (Sweden)

Gliceria B Ramos

2017-01-01

Full Text Available Objective: To investigate if the protective effect of α-tocopherol against the impact of ethanol on brain morphogenesis involved the activity of the selenoproteins phospholipid hydroperoxide glutathione peroxidase (PHGPx; GPx4 and selenoprotein P (SelPP that have roles against oxidative stress. Methods: Forty female mice were randomly assigned into natural control (CON, positive control (ETOH, low-, medium-, and high-α-tocopherolsupplemented- ethanol groups (LTOC, MTOC, HTOC, respectively. CON received drinking water without ethanol while ETOH, LTOC, MTOC and HTOC groups received 20% ethanol in drinking water. The supplemented groups were given respective dosages of α-tocopherol, 0.410, 0.819, and 1.640 mg/g body weight, at day 14 before mating onwards to the day 9 of gestation. At 10.5 ED of gestation (1 100 h, the pregnant females were sacrificed by cervical dislocation and the embryos were harvested. Total RNA were extracted, cDNA synthesis and qRT- PCR analyses were carried out. Results: The level of expression of PHGPx in the positive control was significantly lower than that of the natural control. Among the three α- tocopherol-supplemented groups, only the medium dose- group was significantly higher than the positive control. The level of expression of SelPP in the positive control was significantly lower than those of the natural control, the low- and medium- dose α-tocopherol supplemented groups. In the high dose-α-tocopherol supplemented group, the level of expression was not significantly different from the positive control but significantly lower than the natural control. Conclusions: The activity of the selenoproteins PHGPx and SelPP are involved in the internetwork of antioxidative enzymes with vitamin E when given up to a medium dose only and is one of the possible pathways of shielding embryonic development against the impact of ethanol on brain morphogenesis. This study strengthens the impact of dietaryα-tocopherol and

Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

International Nuclear Information System (INIS)

Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

1985-01-01

Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1- 14 C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis

G-rich, a Drosophila selenoprotein, is a Golgi-resident type III membrane protein

International Nuclear Information System (INIS)

Chen, Chang Lan; Shim, Myoung Sup; Chung, Jiyeol; Yoo, Hyun-Seung; Ha, Ji Min; Kim, Jin Young; Choi, Jinmi; Zang, Shu Liang; Hou, Xiao; Carlson, Bradley A.; Hatfield, Dolph L.; Lee, Byeong Jae

2006-01-01

G-rich is a Drosophila melanogaster selenoprotein, which is a homologue of human and mouse SelK. Subcellular localization analysis using GFP-tagged G-rich showed that G-rich was localized in the Golgi apparatus. The fusion protein was co-localized with the Golgi marker proteins but not with an endoplasmic reticulum (ER) marker protein in Drosophila SL2 cells. Bioinformatic analysis of G-rich suggests that this protein is either type II or type III transmembrane protein. To determine the type of transmembrane protein experimentally, GFP-G-rich in which GFP was tagged at the N-terminus of G-rich, or G-rich-GFP in which GFP was tagged at the C-terminus of G-rich, were expressed in SL2 cells. The tagged proteins were then digested with trypsin, and analyzed by Western blot analysis. The results showed that the C-terminus of the G-rich protein was exposed to the cytoplasm indicating it is a type III microsomal membrane protein. G-rich is First selenoprotein identified in the Golgi apparatus

Decreased plasma thiol antioxidant barrier and selenoproteins as potential biomarkers for ongoing methylmercury intoxication and an individual protective capacity.

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Usuki, Fusako; Fujimura, Masatake

2016-04-01

Manifestation of methylmercury (MeHg) toxicity depends on individual susceptibility to MeHg, as well as MeHg burden level. Therefore, biomarkers that reflect the protective capacity against MeHg are needed. The critical role of oxidative stress in the pathogenesis of MeHg cytotoxicity has been demonstrated. Because MeHg has high affinity for selenohydryl groups, sulfhydryl groups, and selenides, and causes posttranscriptional defects in selenoenzymes, proteins with selenohydryl and sulfhydryl groups should play a critical role in mediating MeHg-induced oxidative stress. Here, plasma oxidative stress markers and selenoproteins were investigated in MeHg-intoxicated rats showing neuropathological changes after 4 weeks of MeHg exposure. The thiol antioxidant barrier (-SHp) level significantly decreased 2 weeks after MeHg exposure, which is an early stage at which no systemic oxidative stress, histopathological changes, or clinical signs were detected. Diacron reactive oxidant metabolite (d-ROM) levels significantly increased 3 weeks after MeHg exposure, indicating the occurrence of systemic oxidative stress. Rats treated with lead acetate or cadmium chloride showed no changes in levels of -SHp and d-ROM. Selenoprotein P1 abundance significantly decreased in MeHg-treated rats, whereas it significantly increased in rats treated with Pb or Cd. Plasma selenium-dependent glutathione peroxidase (GPx3) activity also significantly decreased after MeHg exposure, whereas plasma non-selenoenzyme glutathione reductase activity significantly increased in MeHg-treated rats. The results suggest that decreased capacity of -SHp and selenoproteins (GPx3 and selenoprotein P) can be useful biomarkers of ongoing MeHg cytotoxicity and the individual protective capacity against the MeHg body burden.

Selenoproteins in human body: focus on thyroid pathophysiology.

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Valea, Ana; Georgescu, Carmen Emanuela

2018-06-05

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels

Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

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Barrett, Caitlyn W.; Reddy, Vishruth K.; Short, Sarah P.; Motley, Amy K.; Lintel, Mary K.; Bradley, Amber M.; Freeman, Tanner; Vallance, Jefferson; Ning, Wei; Parang, Bobak; Poindexter, Shenika V.; Fingleton, Barbara; Chen, Xi; Washington, Mary K.; Wilson, Keith T.; Shroyer, Noah F.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

2015-01-01

Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions. PMID:26053663

Impaired Homocysteine Transmethylation and Protein-Methyltransferase Activity Reduce Expression of Selenoprotein P: Implications for Obesity and Metabolic Syndrome

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Obesity causes Metabolic Syndrome and Type-II Diabetes, disrupting hepatic function, methionine (Met)/homocysteine (Hcy) transmethylation and methyltransferase (PRMT) activities. Selenoprotein P (SEPP1), exported from the liver, is the predominate form of plasma selenium (Se) and the physiological S...

Comparison of different transition metal ions for immobilized metal affinity chromatography of selenoprotein P from human plasma

DEFF Research Database (Denmark)

Sidenius, U; Farver, O; Jøns, O

1999-01-01

Cu2+, Ni2+, Zn2+, Co2+ and Cd2+ were evaluated in metal ion affinity chromatography for enrichment of selenoprotein P, and immobilized Co2+ affinity chromatography was found to be the most selective chromatographic method. The chromatography was performed by fast protein liquid chromatography...

Serum selenium and selenoprotein P status in adult Danes-8-year followup

DEFF Research Database (Denmark)

Rasmussen, Lone Banke; Hollenbach, B.; Laurberg, P.

2009-01-01

was investigated. Blood samples from a total of 817 randomly selected subjects from two cities in Denmark were analyzed. Half of the samples were collected in 1997-1998 and the other half in 2004-2005. Samples from women aged 18-22, 40-45 and 60-65 years, and men aged 60-65 years were selected for this study. All...... increased with age, and selenoprotein P was higher in men than in women. Serum selenium levels decreased by 5% on average from 1997-98 to 2004-05 (P

Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal cancer.

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Martha L Slattery

Full Text Available BACKGROUND: Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. METHODS: We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls and rectal (n = 754 cases, 959 controls cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH, SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. RESULTS: After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208. Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300. Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR and rectal cancer (SepX1 increased HRR. CONCLUSIONS: Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is

SELENIUM SUBSTITUTION – EFFECT ON THYROID FUNCTION

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Milica Pešić

2015-03-01

Full Text Available The understanding of the essential role of selenium (Se in thyroid hormone synthesis, metabolism and action, as well as normal thyroid function, increased during the past decades. The thyroid gland is among the human tissues with the highest Se content per mas unit, similar to other endocrine organs and brain. Biological actions of Se are mediated, in most cases, through the expression of at least 30 selenoproteins coded by 25 selenoprotein genes in the human. Via the selenoproteins, selenium can influence the cell function through antioxidant activites, modifying redox status and thyroid hormone synthesis and metabolism. Selenoproteins iodothyronine deiodinases are present in most tissues and have a role to increase the production of bioactive tri-iodothyronine. Futhermore, Se has been shown to be important in the regulation of immune function. Se deficiency is accompained by the loss of immune competence. The links between Se deficiency, altered immune function and inflamation have prompted studies in humans to examine if Se suplementation can modify auto-antibodies production in patients with chronic autoimmune thyroiditis. Until now, several randomised prospective clinical trials have been performed in patients with established chronic autoimmune thyrioditis. The clinical endpoint of each study was the decrease in TPO antibodies concentration after 3-12 months of treatment. Ussualy, the dosage of daily Se supplementation was 200µg. Selenium suplemetation had no significant effect on the concentration of TSH or thyroid hormone concentrations. These studies indicate that Se treatment result in reduced inflammatory activity, but it does not cure chronc autoimmune process.

Kissing loops hide premature termination codons in pre-mRNAof selenoprotein genes and in genes containing programmedribosomal frameshifts

DEFF Research Database (Denmark)

Knudsen, Steen; Brunak, Søren

1997-01-01

A novel RNA secondary structure that places the selenocysteine codon UGA in one hairpin and a donor splice site in another, has been discovered in selenoprotein genes. The presence of the structure resolves the discrepancy that the selenocysteine triplet, UGA, should block splicing. Without a spe...

Direct determination of selenoproteins in polyvinylidene difluoride membranes by electrothermal atomic absorption spectrometry

DEFF Research Database (Denmark)

Sidenius, U; Gammelgaard, Bente

2000-01-01

A method for the direct determination of selenoproteins in plastic membranes after protein separation by gel electrophoresis was developed. Quantification was based on the determination of the selenium content of the proteins by electrothermal atomic absorption spectrometry (ET-AAS) after manual...... were excised and chemical modifier was added on top of the excised membrane prior to atomic absorption measurement. Acceptable linearity was achieved in the range 2-10 ng Se, corresponding to selenium concentrations close to 1 mg/L, when aqueous solutions of selenomethionine standard as well...

Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States

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Chen, Richard J.; Zhang, Guofeng; Garfield, Susan H.; Shi, Yi-Jun; Chen, Kevin G.; Robey, Pamela G.; Leapman, Richard D.

2015-01-01

Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions. PMID:26565809

Influence of different genotypes in the pattern of selenoprotein expression in response to Brazil nut supplementation

OpenAIRE

Janaina Lombello Santos Donadio

2016-01-01

The micronutrient selenium is essential to human physiology. As the amino acid selenocysteine, it is inserted into selenoproteins with a wide range of functions including antioxidant capacity, thyroid hormone metabolism, improvement of immune system, brain function, fertility and reproduction. Low selenium status has been associated with increased risk for chronic diseases, such as cancer, type-2 diabetes and cardiovascular disease. In this context, several studies have been conducted in orde...

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

International Nuclear Information System (INIS)

Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

2013-01-01

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

Energy Technology Data Exchange (ETDEWEB)

Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

2013-04-15

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

Biomonitoring of selenoprotein P in human serum by fast affinity chromatography coupled to ICP-MS.

Science.gov (United States)

Heitland, Peter; Köster, Helmut D

2018-04-01

Most of the Se in human serum is bound to selenoprotein P (SEPP1) in which Se is present in form of selenocysteine. The SEPP1 is a new possible biomarker for the Se status and for this reason we developed a fast, simple and reliable method for the quantitative determination of SEPP1 in serum by affinity chromatography coupled to ICP-MS. It is possible to separate SEPP1 from other selenoproteins in serum in only 5 min, which allows high sample throughput in clinical laboratories. Measured and certified concentrations of total Se and Se(SEPP1) are in good agreement for the reference material SRM 1950. The SEPP1 concentration was stable in serum samples of 3 persons for a minimum of 2 weeks. Further results of method validation were described including internal and external quality assurance. The analytical method was applied for a biomonitoring study of the SEPP1 and total Se concentration in human serum of 50 occupationally non-exposed persons living in northern Germany. Concentration ranges and mean concentrations for Se(SEPP1) are 31.1-59.7 and 46.2 μg/L, respectively. The corresponding values for total Se are 62-120 and 83.5 μg/L. The mean percentage of total Se in serum present as SEPP1 is 58%. Copyright © 2018 Elsevier GmbH. All rights reserved.

Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks.

Science.gov (United States)

Yao, Hai-Dong; Wu, Qiong; Zhang, Zi-Wei; Zhang, Jiu-Li; Li, Shu; Huang, Jia-Qiang; Ren, Fa-Zheng; Xu, Shi-Wen; Wang, Xiao-Long; Lei, Xin Gen

2013-05-01

Dietary selenium (Se) deficiency causes muscular dystrophy in various species, but the molecular mechanism remains unclear. Our objectives were to investigate: 1) if dietary Se deficiency induced different amounts of oxidative stress, lipid peroxidation, and cell apoptosis in 3 skeletal muscles; and 2) if the distribution and expression of 4 endoplasmic reticulum (ER) resident selenoprotein genes (Sepn1, Selk, Sels, and Selt) were related to oxidative damages in these muscles. Two groups of day-old layer chicks (n = 60/group) were fed a corn-soy basal diet (33 μg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or the diet supplemented with Se (as sodium selenite) at 0.15 mg/kg for 55 d. Dietary Se deficiency resulted in accelerated (P muscles. All these responses were stronger in the pectoral muscle than in the thigh and wing muscles (P muscles. Expression of Sepn1, Sels, and Selt in these muscles was correlated with (r > 0.72; P muscle demonstrated unique expression patterns of the ER resident selenoprotein genes and GPx activity, along with elevated susceptibility to oxidative cell death, compared with the other skeletal muscles. These features might help explain why it is a primary target of Se deficiency diseases in chicks.

Green tea extracts reduce leukocyte cell-Derived chemotaxin 2 and selenoprotein P levels in the livers of C57BL/6J mice fed a high-fat diet.

Science.gov (United States)

Onishi, Shintaro; Kitazawa, Hidefumi; Meguro, Shinichi; Tokimitsu, Ichiro

2018-05-31

Epidemiological studies suggest that green tea extracts (GTEs), including catechins such as epigallocatechin gallate and epicatechin gallate, have a beneficial effect on obesity, hyperglycemia, insulin resistance, endothelial dysfunction, and inflammation. Although several studies have shown that catechins directly modulate the cellular and molecular alterations in the liver tissue, the contributions of indirect mechanisms underlying these systemic effects of catechins remain unclear. In this study, we report that, in the C57BL/6J mouse liver, GTEs reduce high-fat diet-induced increases in the levels of hepatokines, liver-derived secretary proteins such as leukocyte cell-derived chemotaxin 2 and selenoprotein P production, which have been shown to induce systemic adverse effects, including several metabolic diseases. These findings suggest that the systemic effects of GTEs involve the regulation of hepatokine production as an indirect mechanism.

Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

Science.gov (United States)

Ansoleaga, Belén; Garcia-Esparcia, Paula; Llorens, Franc; Hernández-Ortega, Karina; Carmona Tech, Margarita; Antonio Del Rio, José; Zerr, Inga; Ferrer, Isidro

2016-06-12

Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Altered Machinery of Protein Synthesis in Alzheimer's: From the Nucleolus to the Ribosome.

Science.gov (United States)

Hernández-Ortega, Karina; Garcia-Esparcia, Paula; Gil, Laura; Lucas, José J; Ferrer, Isidre

2016-09-01

Ribosomes and protein synthesis have been reported to be altered in the cerebral cortex at advanced stages of Alzheimer's disease (AD). Modifications in the hippocampus with disease progression have not been assessed. Sixty-seven cases including middle-aged (MA) and AD stages I-VI were analyzed. Nucleolar chaperones nucleolin, nucleophosmin and nucleoplasmin 3, and upstream binding transcription factor RNA polymerase I gene (UBTF) mRNAs are abnormally regulated and their protein levels reduced in AD. Histone modifications dimethylated histone H3K9 (H3K9me2) and acetylated histone H3K12 (H3K12ac) are decreased in CA1. Nuclear tau declines in CA1 and dentate gyrus (DG), and practically disappears in neurons with neurofibrillary tangles. Subunit 28 ribosomal RNA (28S rRNA) expression is altered in CA1 and DG in AD. Several genes encoding ribosomal proteins are abnormally regulated and protein levels of translation initiation factors eIF2α, eIF3η and eIF5, and elongation factor eEF2, are altered in the CA1 region in AD. These findings show alterations in the protein synthesis machinery in AD involving the nucleolus, nucleus and ribosomes in the hippocampus in AD some of them starting at first stages (I-II) preceding neuron loss. These changes may lie behind reduced numbers of dendritic branches and reduced synapses of CA1 and DG neurons which cause hippocampal atrophy. © 2015 International Society of Neuropathology.

Sexual Dimorphism in the Selenocysteine Lyase Knockout Mouse.

Science.gov (United States)

Ogawa-Wong, Ashley N; Hashimoto, Ann C; Ha, Herena; Pitts, Matthew W; Seale, Lucia A; Berry, Marla J

2018-01-31

Selenium (Se) is an essential micronutrient known for its antioxidant properties and health benefits, attributed to its presence in selenoproteins as the amino acid, selenocysteine. Selenocysteine lyase (Scly) catalyzes hydrolysis of selenocysteine to selenide and alanine, facilitating re-utilization of Se for de novo selenoprotein synthesis. Previously, it was reported that male Scly -/- mice develop increased body weight and body fat composition, and altered lipid and carbohydrate metabolism, compared to wild type mice. Strikingly, females appeared to present with a less severe phenotype, suggesting the relationship between Scly and energy metabolism may be regulated in a sex-specific manner. Here, we report that while body weight and body fat gain occur in both male and female Scly -/- mice, strikingly, males are susceptible to developing glucose intolerance, whereas female Scly -/- mice are protected. Because Se is critical for male reproduction, we hypothesized that castration would attenuate the metabolic dysfunction observed in male Scly -/- mice by eliminating sequestration of Se in testes. We report that fasting serum insulin levels were significantly reduced in castrated males compared to controls, but islet area was unchanged between groups. Finally, both male and female Scly -/- mice exhibit reduced hypothalamic expression of selenoproteins S, M, and glutathione peroxidase 1.

Sexual Dimorphism in the Selenocysteine Lyase Knockout Mouse

Directory of Open Access Journals (Sweden)

Ashley N. Ogawa-Wong

2018-01-01

Full Text Available Selenium (Se is an essential micronutrient known for its antioxidant properties and health benefits, attributed to its presence in selenoproteins as the amino acid, selenocysteine. Selenocysteine lyase (Scly catalyzes hydrolysis of selenocysteine to selenide and alanine, facilitating re-utilization of Se for de novo selenoprotein synthesis. Previously, it was reported that male Scly−/− mice develop increased body weight and body fat composition, and altered lipid and carbohydrate metabolism, compared to wild type mice. Strikingly, females appeared to present with a less severe phenotype, suggesting the relationship between Scly and energy metabolism may be regulated in a sex-specific manner. Here, we report that while body weight and body fat gain occur in both male and female Scly−/− mice, strikingly, males are susceptible to developing glucose intolerance, whereas female Scly−/− mice are protected. Because Se is critical for male reproduction, we hypothesized that castration would attenuate the metabolic dysfunction observed in male Scly−/− mice by eliminating sequestration of Se in testes. We report that fasting serum insulin levels were significantly reduced in castrated males compared to controls, but islet area was unchanged between groups. Finally, both male and female Scly−/− mice exhibit reduced hypothalamic expression of selenoproteins S, M, and glutathione peroxidase 1.

Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice

Directory of Open Access Journals (Sweden)

Petra A. Tsuji

2015-08-01

Full Text Available Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif

Science.gov (United States)

Shchedrina, Valentina A.; Novoselov, Sergey V.; Malinouski, Mikalai Yu.; Gladyshev, Vadim N.

2007-01-01

Selenocysteine (Sec, U) insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element. Selenoproteins with known functions are oxidoreductases containing a single redox-active Sec in their active sites. In this work, we identified a family of selenoproteins, designated SelL, containing two Sec separated by two other residues to form a UxxU motif. SelL proteins show an unusual occurrence, being present in diverse aquatic organisms, including fish, invertebrates, and marine bacteria. Both eukaryotic and bacterial SelL genes use single SECIS elements for insertion of two Sec. In eukaryotes, the SECIS is located in the 3′ UTR, whereas the bacterial SelL SECIS is within a coding region and positioned at a distance that supports the insertion of either of the two Sec or both of these residues. SelL proteins possess a thioredoxin-like fold wherein the UxxU motif corresponds to the catalytic CxxC motif in thioredoxins, suggesting a redox function of SelL proteins. Distantly related SelL-like proteins were also identified in a variety of organisms that had either one or both Sec replaced with Cys. Danio rerio SelL, transiently expressed in mammalian cells, incorporated two Sec and localized to the cytosol. In these cells, it occurred in an oxidized form and was not reducible by DTT. In a bacterial expression system, we directly demonstrated the formation of a diselenide bond between the two Sec, establishing it as the first diselenide bond found in a natural protein. PMID:17715293

Mutants of Cercospora kikuchii altered in cercosporin synthesis and pathogenicity

International Nuclear Information System (INIS)

Upchurch, R.G.; Walker, D.C.; Rollins, J.A.; Ehrenshaft, M.; Daub, M.E.

1991-01-01

The authors have obtained spontaneous and UV-induced stable mutants, altered in the synthesis of cercosporin, of the fungal soybean pathogen Cercospora kikuchii. The mutants were isolated on the basis of colony color on minimal medium. The UV-induced mutants accumulated, at most, 2% of wild-type cercosporin levels on all media tested. In contrast, cercosporin accumulation by the spontaneous mutants was strongly medium regulated, occurring only on potato dextrose medium but at concentrations comparable to those produced by the wild-type strain. UV-induced mutants unable to synthesize cercosporin on any medium were unable to incite lesions when inoculated onto the soybean host. Cercosporin was reproducibly isolated from all inoculated leaves showing lesions. Although cercosporin involvement in disease has been indirectly suggested by many previous studies, this is the first report in which mutants blocked in cercosporin synthesis have been used to demonstrate that cercosporin is a crucial pathogenicity factor for this fungal genus

Determination of selenoprotein P in human plasma by solid phase extraction and inductively coupled plasma mass spectrometry

DEFF Research Database (Denmark)

Bendahl, L.; Sidenius, U.; Gammelgaard, Bente

2000-01-01

measured by inductively coupled plasma mass spectrometry (ICP-MS) monitoring the Se-82 isotope. Linear response was observed in the concentration range 0.3-70.8 mu g/l selenium as selenoprotein P with a correlation coefficient of 0.9994. The precision expressed as relative standard deviation was better...... than 2% in this range. The estimated limit of detection was 2 mu g/l and the experimentally verified quantification limit was 5 mu g/l, giving a relative standard deviation less than 2%. (C) 2000 Elsevier Science B.V. All rights reserved...

Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

Energy Technology Data Exchange (ETDEWEB)

Goodrich, Jaclyn M.; Wang, Yi [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Gillespie, Brenda [Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Werner, Robert [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower Parkway Suite 100, Ann Arbor, MI 48108 (United States); Franzblau, Alfred [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Basu, Niladri, E-mail: niladri@umich.edu [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States)

2011-12-15

Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 {+-} 1.24 ug/L) and hair mercury levels (0.49 {+-} 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5 Prime ), or both (SEPP1 3 Prime UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: Black-Right-Pointing-Pointer We explore the influence of 15 polymorphisms on urine and hair Hg levels. Black-Right-Pointing-Pointer Urine and hair Hg levels in dental professionals were similar to the US population. Black-Right-Pointing-Pointer GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. Black

Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

International Nuclear Information System (INIS)

Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri

2011-01-01

Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 ± 1.24 ug/L) and hair mercury levels (0.49 ± 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5′), or both (SEPP1 3′UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: ► We explore the influence of 15 polymorphisms on urine and hair Hg levels. ► Urine and hair Hg levels in dental professionals were similar to the US population. ► GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. ► Accumulation of Hg in hair following exposure from fish was modified by genotype. ► GSTP1, GSS

Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases

Directory of Open Access Journals (Sweden)

Díaz-Rubio Manuel

2008-07-01

Full Text Available Abstract Background Selenoprotein S (SelS protects the functional integrity of the endoplasmic reticulum against the deleterious effects of metabolic stress. SEPS1/SelS polymorphisms have been involved in the increased release of pro-inflammatory cytokines interleukin (IL-1β, tumor necrosis factor (TNF-α and IL-6 in macrophages. We aimed at investigating the role of the SEPS1 variants previously associated with higher plasma levels of these cytokines and of the SEPS1 haplotypes in the susceptibility to develop immune-mediated diseases characterized by an inflammatory component. Results Six polymorphisms distributed through the SEPS1 gene (rs11327127, rs28665122, rs4965814, rs12917258, rs4965373 and rs2101171 were genotyped in more than two thousand patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases and 550 healthy controls included in the case-control study. Conclusion Lack of association of SEPS1 polymorphisms or haplotypes precludes a major role of this gene increasing predisposition to these inflammatory diseases.

Interactions ARN-protéines dans le mécanisme de biosynthèse des sélénoprotéines

OpenAIRE

Takeuchi , Akiko

2009-01-01

The 21st amino acid selenocysteine is encoded by a UGA codon that usually signifies translational termination. Selenoprotein synthesis therefore requires specialized factors. Among these is SBP2 that binds the SECIS, a stem-loop structure in the 3'UTR of selenoprotein mRNAs. In structural analyses of SBP2, we isolated and functionally characterized Drosophila melanogaster SBP2. By comparing it with human SBP2, we identified an additional RNA binding domain that is essential for SECIS and 60S ...

Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice*

OpenAIRE

Kasaikina, Marina V.; Fomenko, Dmitri E.; Labunskyy, Vyacheslav M.; Lachke, Salil A.; Qiu, Wenya; Moncaster, Juliet A.; Zhang, Jie; Wojnarowicz, Mark W.; Natarajan, Sathish Kumar; Malinouski, Mikalai; Schweizer, Ulrich; Tsuji, Petra A.; Carlson, Bradley A.; Maas, Richard L.; Lou, Marjorie F.

2011-01-01

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteine-rich UDP-gl...

Selenium regulates gene expression of selenoprotein W in chicken skeletal muscle system.

Science.gov (United States)

Ruan, Hongfeng; Zhang, Ziwei; Wu, Qiong; Yao, Haidong; Li, Jinlong; Li, Shu; Xu, Shiwen

2012-01-01

Selenoprotein W (SelW) is abundantly expressed in skeletal muscles of mammals and necessary for the metabolism of skeletal muscles. However, its expression pattern in skeletal muscle system of birds is still uncovered. Herein, to investigate the distribution of SelW mRNA in chicken skeletal muscle system and its response to different selenium (Se) status, 1-day-old chickens were exposed to various concentrations of Se as sodium selenite in the feed for 35 days. In addition, myoblasts were treated with different concentrations of Se in the medium for 72 h. Then the levels of SelW mRNA in skeletal muscles (wing muscle, pectoral muscle, thigh muscle) and myoblasts were determined on days 1, 15, 25, and 35 and at 0, 24, 48, and 72 h, respectively. The results showed that SelW was detected in all these muscle components and it increased both along with the growth of organism and the differentiation process of myoblasts. The thigh muscle is more responsive to Se intake than the other two skeletal muscle tissues while the optimal Se supplementation for SelW mRNA expression in chicken myoblasts was 10(-7) M. In summary, Se plays important roles in the development of chicken skeletal muscles. To effect optimal SelW gene expression, Se must be provided in the diet and the media in adequate amounts and neither at excessive nor deficient levels.

Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

LENUS (Irish Health Repository)

Kelly, Emer

2009-06-19

Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.

Alteration of cardiac glycoside positive inotropic action by modulators of protein synthesis and degradation

International Nuclear Information System (INIS)

Nosek, T.M.; Adams, R.J.

1986-01-01

Numerous membrane bound and cytoplasmic proteins participate in the cardiac expression of the positive inotropic action (PIA) of digitalis glycosides including the Na,K-ATPase (NKA). Exposure of the myocardium to an inhibitor of protein synthesis (cycloheximide, CYC) or of protein degradation (leupeptin, LEU) alters the PIA of ouabain in isolated, paced guinea pig papillary muscles (PM) in opposite ways. In vivo exposure to CYC for 3 hr resulted in a 30% depression of the in vitro PIA of ouabain at 1.7μM compared to control. In vivo exposure to LEU for 1 hr resulted in a 47% enhancement of the in vitro PIA of 1.7μM ouabain. Neither drug had an apparent effect on the ouabain PIA ED50. Neither CYC nor LEU exposure to PM in vitro affect resting or developed tension or the response of skinned PM to calcium. The mechanisms of the PIA alterations by CYC or LEU do not involve a direct effect on the digitalis receptor. Exposure of isolated cardiac sarcolemma enriched in NKA to 10-100μM CYC or LEU did not affect NKA activity or 3 H-ouabain binding. Although direct physicochemical effects of CYC or LEU may be involved in the alterations of the ouabain PIA, it is possible that modulation of the cellular levels or turnover rate of short-lived proteins may affect cardiac regulation of the digitalis PIA

The effect of dietary bacterial organic selenium on growth performance, antioxidant capacity, and Selenoproteins gene expression in broiler chickens.

Science.gov (United States)

Dalia, A M; Loh, T C; Sazili, A Q; Jahromi, M F; Samsudin, A A

2017-08-18

Selenium (Se) is an essential trace mineral in broilers, which has several important roles in biological processes. Organic forms of Se are more efficient than inorganic forms and can be produced biologically via Se microbial reduction. Hence, the possibility of using Se-enriched bacteria as feed supplement may provide an interesting source of organic Se, and benefit broiler antioxidant system and other biological processes. The objective of this study was to examine the impacts of inorganic Se and different bacterial organic Se sources on the performance, serum and tissues Se status, antioxidant capacity, and liver mRNA expression of selenoproteins in broilers. Results indicated that different Se sources did not significantly (P ≤ 0.05) affect broiler growth performance. However, bacterial organic Se of T5 (basal diet +0.3 mg /kg feed ADS18 Se), T4 (basal diet +0.3 mg /kg feed ADS2 Se), and T3 (basal diet +0.3 mg /kg feed ADS1 Se) exhibited significantly (P ≤ 0.05) highest Se concentration in serum, liver, and kidney respectively. Dietary inorganic Se and bacterial organic Se were observed to significantly affect broiler serum ALT, AST, LDH activities and serum creatinine level. ADS18 supplemented Se of (Stenotrophomonas maltophilia) bacterial strain showed the highest GSH-Px activity with the lowest MDA content in serum, and the highest GSH-Px and catalase activity in the kidney, while bacterial Se of ADS2 (Klebsiella pneumoniae) resulted in a higher level of GSH-Px1 and catalase in liver. Moreover, our study showed that in comparison with sodium selenite, only ADS18 bacterial Se showed a significantly higher mRNA level in GSH-Px1, GSH-Px4, DIO1, and TXNDR1, while both ADS18 and ADS2 showed high level of mRNA of DIO2 compared to sodium selenite. The supplementation of bacterial organic Se in broiler chicken, improved tissue Se deposition, antioxidant status, and selenoproteins gene expression, and can be considered as an effective alternative source of

Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk

DEFF Research Database (Denmark)

Méplan, Catherine; Dragsted, Lars Ove; Ravn-Haren, Gitte

2013-01-01

Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases...... and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional...... logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro...

Selenium deficiency occurs in some patients with moderate-to-severe cirrhosis and can be corrected by administration of selenate but not selenomethionine: a randomized controlled trial123

Science.gov (United States)

Burk, Raymond F; Hill, Kristina E; Motley, Amy K; Byrne, Daniel W; Norsworthy, Brooke K

2015-01-01

Background: Selenomethionine, which is the principal dietary form of selenium, is metabolized by the liver to selenide, which is the form of the element required for the synthesis of selenoproteins. The liver synthesizes selenium-rich selenoprotein P (SEPP1) and secretes it into the plasma to supply extrahepatic tissues with selenium. Objectives: We conducted a randomized controlled trial to determine whether cirrhosis is associated with functional selenium deficiency (the lack of selenium for the process of selenoprotein synthesis even though selenium intake is not limited) and, if it is, whether the deficiency is associated with impairment of selenomethionine metabolism. Design: Patients with Child-Pugh (C-P) classes A, B, and C (mild, moderate, and severe, respectively) cirrhosis were supplemented with a placebo or supranutritional amounts of selenium as selenate (200 or 400 μg/d) or as selenomethionine (200 μg/d) for 4 wk. Plasma SEPP1 concentration and glutathione peroxidase (GPX) activity, the latter due largely to the selenoprotein GPX3 secreted by the kidneys, were measured before and after supplementation. Results: GPX activity was increased more by both doses of selenate than by the placebo in C-P class B patients. The activity was not increased more by selenomethionine supplementation than by the placebo in C-P class B patients. Plasma selenium was increased more by 400 μg Se as selenate than by the placebo in C-P class C patients. Within the groups who responded to selenate, there was a considerable variation in responses. Conclusion: These results indicate that severe cirrhosis causes mild functional selenium deficiency in some patients that is associated with impaired metabolism of selenomethionine. This trial was registered at clinicaltrials.gov as NCT00271245. PMID:26468123

The central role of selenium in the biochemistry and ecology of the harmful pelagophyte, Aureococcus anophagefferens

Energy Technology Data Exchange (ETDEWEB)

Gobler, Christopher J.; Lobanov, Alexei V.; Tang, Ying-Zhong; Turanov, Anton A.; Zhang, Yan; Doblin, Martina; Taylor, Gordon T.; Sañudo-Wilhelmy, Sergio A.; Grigoriev, Igor V.; Gladyshev, Vadim N.

2013-03-07

The trace element selenium (Se) is required for the biosynthesis of selenocysteine (Sec), the 21st amino acid in the genetic code, but its role in the ecology of harmful algal blooms (HABs) is unknown. Here, we examined the role of Se in the biology and ecology of the harmful pelagophyte, Aureococcus anophagefferens, through cell culture, genomic analyses, and ecosystem studies. This organism has the largest and the most diverse selenoproteome identified to date that consists of at least 59 selenoproteins, including known eukaryotic selenoproteins, selenoproteins previously only detected in bacteria, and novel selenoproteins. The A. anophagefferens selenoproteome was dominated by the thioredoxin fold proteins and oxidoreductase functions were assigned to the majority of detected selenoproteins. Insertion of Sec in these proteins was supported by a unique Sec insertion sequence. Se was required for the growth of A. anophagefferens as cultures grew maximally at nanomolar Se concentrations. In a coastal ecosystem, dissolved Se concentrations were elevated before and after A. anophagefferens blooms, but were reduced by >95percent during the peak of blooms to 0.05 nM. Consistent with this pattern, enrichment of seawater with selenite before and after a bloom did not affect the growth of A. anophagefferens, but enrichment during the peak of the bloom significantly increased population growth rates. These findings demonstrate that Se inventories, which can be anthropogenically enriched, can support proliferation of HABs, such as A. anophagefferens through its synthesis of a large arsenal of Se-dependent oxidoreductases that fine-tune cellular redox homeostasis.

Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish.

Science.gov (United States)

Li, Jia-Min; Li, Ling-Yu; Qin, Xuan; Degrace, Pascal; Demizieux, Laurent; Limbu, Samwel M; Wang, Xin; Zhang, Mei-Ling; Li, Dong-Liang; Du, Zhen-Yu

2018-01-01

Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW)/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG) concentrations, fatty acid (FA) β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin ( mtor ), and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model could also be

Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish

Directory of Open Access Journals (Sweden)

Jia-Min Li

2018-05-01

Full Text Available Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG concentrations, fatty acid (FA β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin (mtor, and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model

Chlorophyll Synthase under Epigenetic Surveillance Is Critical for Vitamin E Synthesis, and Altered Expression Affects Tocopherol Levels in Arabidopsis.

Science.gov (United States)

Zhang, Chunyu; Zhang, Wei; Ren, Guodong; Li, Delin; Cahoon, Rebecca E; Chen, Ming; Zhou, Yongming; Yu, Bin; Cahoon, Edgar B

2015-08-01

Chlorophyll synthase catalyzes the final step in chlorophyll biosynthesis: the esterification of chlorophyllide with either geranylgeranyl diphosphate or phytyl diphosphate (PDP). Recent studies have pointed to the involvement of chlorophyll-linked reduction of geranylgeranyl by geranylgeranyl reductase as a major pathway for the synthesis of the PDP precursor of tocopherols. This indirect pathway of PDP synthesis suggests a key role of chlorophyll synthase in tocopherol production to generate the geranylgeranyl-chlorophyll substrate for geranylgeranyl reductase. In this study, contributions of chlorophyll synthase to tocopherol formation in Arabidopsis (Arabidopsis thaliana) were explored by disrupting and altering expression of the corresponding gene CHLOROPHYLL SYNTHASE (CHLSYN; At3g51820). Leaves from the homozygous chlysyn1-1 null mutant were nearly devoid of tocopherols, whereas seeds contained only approximately 25% of wild-type tocopherol levels. Leaves of RNA interference lines with partial suppression of CHLSYN displayed marked reductions in chlorophyll but up to a 2-fold increase in tocopherol concentrations. Cauliflower mosaic virus35S-mediated overexpression of CHLSYN unexpectedly caused a cosuppression phenotype at high frequencies accompanied by strongly reduced chlorophyll content and increased tocopherol levels. This phenotype and the associated detection of CHLSYN-derived small interfering RNAs were reversed with CHLSYN overexpression in rna-directed rna polymerase6 (rdr6), which is defective in RNA-dependent RNA polymerase6, a key enzyme in sense transgene-induced small interfering RNA production. CHLSYN overexpression in rdr6 had little effect on chlorophyll content but resulted in up to a 30% reduction in tocopherol levels in leaves. These findings show that altered CHLSYN expression impacts tocopherol levels and also, show a strong epigenetic surveillance of CHLSYN to control chlorophyll and tocopherol synthesis. © 2015 American Society of

Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort-Reward Imbalance Model.

Science.gov (United States)

Siegrist, Johannes; Li, Jian

2017-11-10

While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression), additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model-effort-reward imbalance-with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort-reward imbalance, with incident stress-related disorders.

Selenium-regulated hierarchy of human selenoproteome in cancerous and immortalized cells lines.

Science.gov (United States)

Touat-Hamici, Zahia; Bulteau, Anne-Laure; Bianga, Juliusz; Jean-Jacques, Hélène; Szpunar, Joanna; Lobinski, Ryszard; Chavatte, Laurent

2018-04-13

Selenoproteins (25 genes in human) co-translationally incorporate selenocysteine using a UGA codon, normally used as a stop signal. The human selenoproteome is primarily regulated by selenium bioavailability with a tissue-specific hierarchy. We investigated the hierarchy of selenoprotein expression in response to selenium concentration variation in four cell lines originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno-detection, (iv) selenium-specific mass spectrometric detection after non-radioactive 76 Se labeling of selenoproteins, and (v) luciferase-based reporter constructs in various cell extracts. We characterized cell-line specific alterations of the selenoproteome in response to selenium variation that, in most of the cases, resulted from a translational control of gene expression. We established that UGA-selenocysteine recoding efficiency, which depends on the nature of the SECIS element, dictates the response to selenium variation. We characterized that selenoprotein hierarchy is cell-line specific with conserved features. This analysis should be done prior to any experiments in a novel cell line. We reported a strategy based on complementary methods to evaluate selenoproteome regulation in human cells in culture. Copyright © 2018 Elsevier B.V. All rights reserved.

Nano-Se Assimilation and Action in Poultry and Other Monogastric Animals: Is Gut Microbiota an Answer?

Science.gov (United States)

Surai, Peter F.; Kochish, Ivan I.; Velichko, Oksana A.

2017-12-01

Recently, a comprehensive review paper devoted to roles of nano-Se in livestock and fish nutrition has been published in the Nanoscale Research Letters. The authors described in great details an issue related to nano-Se production and its possible applications in animal industry and medicine. However, molecular mechanisms of nano-Se action were not described and the question of how nano-Se is converted into active selenoproteins is not resolved. It seems likely that the gut microbiota can convert nano-Se into selenite, H2Se or Se-phosphate with the following synthesis of selenoproteins. This possibility needs to be further studied in detail, and advantages and disadvantages of nano-Se as a source of Se in animal/poultry/fish nutrition await critical evaluations.

Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Guo, Lei [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Xiao, Yongsheng [Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States); Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States)

2014-05-15

Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort–Reward Imbalance Model

Science.gov (United States)

Siegrist, Johannes; Li, Jian

2017-01-01

While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression), additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model—effort-reward imbalance—with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort–reward imbalance, with incident stress-related disorders. PMID:29125555

Work Stress and Altered Biomarkers: A Synthesis of Findings Based on the Effort–Reward Imbalance Model

Directory of Open Access Journals (Sweden)

Johannes Siegrist

2017-11-01

Full Text Available While epidemiological studies provide statistical evidence on associations of exposures such as stressful work with elevated risks of stress-related disorders (e.g., coronary heart disease or depression, additional information on biological pathways and biomarkers underlying these associations is required. In this contribution, we summarize the current state of the art on research findings linking stressful work, in terms of an established theoretical model—effort-reward imbalance—with a broad range of biomarkers. Based on structured electronic literature search and recent available systematic reviews, our synthesis of findings indicates that associations of work stress with heart rate variability, altered blood lipids, and risk of metabolic syndrome are rather consistent and robust. Significant relationships with blood pressure, heart rate, altered immune function and inflammation, cortisol release, and haemostatic biomarkers were also observed, but due to conflicting findings additional data will be needed to reach a firm conclusion. This narrative review of empirical evidence supports the argument that the biomarkers under study can act as mediators of epidemiologically established associations of work stress, as measured by effort–reward imbalance, with incident stress-related disorders.

Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass

Energy Technology Data Exchange (ETDEWEB)

Martyniuk, Christopher J. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Sanchez, Brian C. [Department of Forestry and Natural Resources and School of Civil Engineering, 195 Marsteller St., Purdue University, West Lafayette, IN 47907 (United States); Szabo, Nancy J.; Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Sepulveda, Maria S., E-mail: mssepulv@purdue.edu [Department of Forestry and Natural Resources and School of Civil Engineering, 195 Marsteller St., Purdue University, West Lafayette, IN 47907 (United States)

2009-10-19

Many aquatic contaminants potentially affect the central nervous system, however the underlying mechanisms of how toxicants alter normal brain function are not well understood. The objectives of this study were to compare the effects of emerging and prevalent environmental contaminants on the expression of brain transcripts with a role in neurotransmitter synthesis and reproduction. Adult male largemouth bass (Micropterus salmoides) were injected once for a 96 h duration with control (water or oil) or with one of two doses of a single chemical to achieve the following body burdens ({mu}g/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl{sub 2}) (0.000067 and 0.00067), polychlorinated biphenyl (PCB) 126 (0.25 and 2.5), and phenanthrene (5 and 50). Partial largemouth bass gene segments were cloned for enzymes involved in neurotransmitter (glutamic acid decarboxylase 65, GAD65; tyrosine hydroxylase) and estrogen (brain aromatase; CYP19b) synthesis for real-time PCR assays. In addition, neuropeptides regulating feeding (neuropeptide Y) and reproduction (chicken GnRH-II, cGnRH-II; salmon GnRH, sGnRH) were also investigated. Of the chemicals tested, only cadmium, PCB 126, and phenanthrene showed any significant effects on the genes tested, while atrazine and toxaphene did not. Cadmium (0.000067 {mu}g/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 {mu}g/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 {mu}g/g) but increased cGnRH-II mRNA at the lowest dose (5 {mu}g/g). CYP19b, NPY, and sGnRH mRNA levels were unaffected by any of the treatments. A hierarchical clustering dendrogram grouped PCB 126 and phenanthrene more closely than other chemicals with respect to the genes tested. This study demonstrates that brain transcripts important for neurotransmitter synthesis neuroendocrine function are potential targets for emerging and prevalent aquatic contaminants.

Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass

International Nuclear Information System (INIS)

Martyniuk, Christopher J.; Sanchez, Brian C.; Szabo, Nancy J.; Denslow, Nancy D.; Sepulveda, Maria S.

2009-01-01

Many aquatic contaminants potentially affect the central nervous system, however the underlying mechanisms of how toxicants alter normal brain function are not well understood. The objectives of this study were to compare the effects of emerging and prevalent environmental contaminants on the expression of brain transcripts with a role in neurotransmitter synthesis and reproduction. Adult male largemouth bass (Micropterus salmoides) were injected once for a 96 h duration with control (water or oil) or with one of two doses of a single chemical to achieve the following body burdens (μg/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl 2 ) (0.000067 and 0.00067), polychlorinated biphenyl (PCB) 126 (0.25 and 2.5), and phenanthrene (5 and 50). Partial largemouth bass gene segments were cloned for enzymes involved in neurotransmitter (glutamic acid decarboxylase 65, GAD65; tyrosine hydroxylase) and estrogen (brain aromatase; CYP19b) synthesis for real-time PCR assays. In addition, neuropeptides regulating feeding (neuropeptide Y) and reproduction (chicken GnRH-II, cGnRH-II; salmon GnRH, sGnRH) were also investigated. Of the chemicals tested, only cadmium, PCB 126, and phenanthrene showed any significant effects on the genes tested, while atrazine and toxaphene did not. Cadmium (0.000067 μg/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 μg/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 μg/g) but increased cGnRH-II mRNA at the lowest dose (5 μg/g). CYP19b, NPY, and sGnRH mRNA levels were unaffected by any of the treatments. A hierarchical clustering dendrogram grouped PCB 126 and phenanthrene more closely than other chemicals with respect to the genes tested. This study demonstrates that brain transcripts important for neurotransmitter synthesis neuroendocrine function are potential targets for emerging and prevalent aquatic contaminants.

Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass.

Science.gov (United States)

Martyniuk, Christopher J; Sanchez, Brian C; Szabo, Nancy J; Denslow, Nancy D; Sepúlveda, Maria S

2009-10-19

Many aquatic contaminants potentially affect the central nervous system, however the underlying mechanisms of how toxicants alter normal brain function are not well understood. The objectives of this study were to compare the effects of emerging and prevalent environmental contaminants on the expression of brain transcripts with a role in neurotransmitter synthesis and reproduction. Adult male largemouth bass (Micropterus salmoides) were injected once for a 96 h duration with control (water or oil) or with one of two doses of a single chemical to achieve the following body burdens (microg/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl(2)) (0.000067 and 0.00067), polychlorinated biphenyl (PCB) 126 (0.25 and 2.5), and phenanthrene (5 and 50). Partial largemouth bass gene segments were cloned for enzymes involved in neurotransmitter (glutamic acid decarboxylase 65, GAD65; tyrosine hydroxylase) and estrogen (brain aromatase; CYP19b) synthesis for real-time PCR assays. In addition, neuropeptides regulating feeding (neuropeptide Y) and reproduction (chicken GnRH-II, cGnRH-II; salmon GnRH, sGnRH) were also investigated. Of the chemicals tested, only cadmium, PCB 126, and phenanthrene showed any significant effects on the genes tested, while atrazine and toxaphene did not. Cadmium (0.000067 microg/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 microg/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 microg/g) but increased cGnRH-II mRNA at the lowest dose (5 microg/g). CYP19b, NPY, and sGnRH mRNA levels were unaffected by any of the treatments. A hierarchical clustering dendrogram grouped PCB 126 and phenanthrene more closely than other chemicals with respect to the genes tested. This study demonstrates that brain transcripts important for neurotransmitter synthesis neuroendocrine function are potential targets for emerging and prevalent aquatic contaminants.

Chlorophyll Synthase under Epigenetic Surveillance Is Critical for Vitamin E Synthesis, and Altered Expression Affects Tocopherol Levels in Arabidopsis1[OPEN

Science.gov (United States)

Zhang, Chunyu; Zhang, Wei; Ren, Guodong; Li, Delin; Cahoon, Rebecca E.; Chen, Ming; Zhou, Yongming; Yu, Bin

2015-01-01

Chlorophyll synthase catalyzes the final step in chlorophyll biosynthesis: the esterification of chlorophyllide with either geranylgeranyl diphosphate or phytyl diphosphate (PDP). Recent studies have pointed to the involvement of chlorophyll-linked reduction of geranylgeranyl by geranylgeranyl reductase as a major pathway for the synthesis of the PDP precursor of tocopherols. This indirect pathway of PDP synthesis suggests a key role of chlorophyll synthase in tocopherol production to generate the geranylgeranyl-chlorophyll substrate for geranylgeranyl reductase. In this study, contributions of chlorophyll synthase to tocopherol formation in Arabidopsis (Arabidopsis thaliana) were explored by disrupting and altering expression of the corresponding gene CHLOROPHYLL SYNTHASE (CHLSYN; At3g51820). Leaves from the homozygous chlysyn1-1 null mutant were nearly devoid of tocopherols, whereas seeds contained only approximately 25% of wild-type tocopherol levels. Leaves of RNA interference lines with partial suppression of CHLSYN displayed marked reductions in chlorophyll but up to a 2-fold increase in tocopherol concentrations. Cauliflower mosaic virus35S-mediated overexpression of CHLSYN unexpectedly caused a cosuppression phenotype at high frequencies accompanied by strongly reduced chlorophyll content and increased tocopherol levels. This phenotype and the associated detection of CHLSYN-derived small interfering RNAs were reversed with CHLSYN overexpression in rna-directed rna polymerase6 (rdr6), which is defective in RNA-dependent RNA polymerase6, a key enzyme in sense transgene-induced small interfering RNA production. CHLSYN overexpression in rdr6 had little effect on chlorophyll content but resulted in up to a 30% reduction in tocopherol levels in leaves. These findings show that altered CHLSYN expression impacts tocopherol levels and also, show a strong epigenetic surveillance of CHLSYN to control chlorophyll and tocopherol synthesis. PMID:26048882

Alterations in protein synthesis in the cyanobacterium Synechococcus sp. Strain PCC 6301 in response to Calendula Micrantha extract with the Molluscicidal activity.

Energy Technology Data Exchange (ETDEWEB)

Hammouda, O H.E. [Botany Department, Faculty of Science, Cairo University, Beni-Suef branch. Beni Suef (Egypt); Borbely, G [Institute of plant physiology, Biological Research Center, Szeged H-6701, (Hungary)

1995-10-01

The response to the extract of the egyptian wild herb Calendula Micrantha, with the Molluscicidal activity, was examined in the unicellular no bacterium Synechococcus sp. strain PCC 6301. growth and chlorophyll of the cells were only slightly affected by low plant extract concentrations but were drastically reduced by high concentration. the rate of protein synthesis progressively decreased by increasing extract concentration. the cells preferentially induced the synthesis of a limited number of polypeptides in response to the treatment. Among the induced polypeptides were those with apparent molecular weights of 161 K (161.000), 96.7 K, 93.4 K, 69.9 K, 59 K, 49 K, 45 K, 35 K, 32.4 K, 28 K, 24 K, 21.7 K, 18 K and 16 K based on their mobilities in gel electrophoresis. these initial studies suggest that the plant extract exerted certain stress which stimulated alteration in the pattern of protein synthesis in Synechococcus sp. some of induced polypeptides are similar to that known to occur in other stresses specially heat shock stress. 3 figs.

Alterations in protein synthesis in the cyanobacterium Synechococcus sp. Strain PCC 6301 in response to Calendula Micrantha extract with the Molluscicidal activity

International Nuclear Information System (INIS)

Hammouda, O.H.E.; Borbely, G.

1995-01-01

The response to the extract of the egyptian wild herb Calendula Micrantha, with the Molluscicidal activity, was examined in the unicellular no bacterium Synechococcus sp. strain PCC 6301. growth and chlorophyll of the cells were only slightly affected by low plant extract concentrations but were drastically reduced by high concentration. the rate of protein synthesis progressively decreased by increasing extract concentration. the cells preferentially induced the synthesis of a limited number of polypeptides in response to the treatment. Among the induced polypeptides were those with apparent molecular weights of 161 K (161.000), 96.7 K, 93.4 K, 69.9 K, 59 K, 49 K, 45 K, 35 K, 32.4 K, 28 K, 24 K, 21.7 K, 18 K and 16 K based on their mobilities in gel electrophoresis. these initial studies suggest that the plant extract exerted certain stress which stimulated alteration in the pattern of protein synthesis in Synechococcus sp. some of induced polypeptides are similar to that known to occur in other stresses specially heat shock stress. 3 figs

Delineating hierarchy of selenotranscriptome expression and their response to selenium status in chicken central nervous system.

Science.gov (United States)

Jiang, Xiu-Qing; Cao, Chang-Yu; Li, Zhao-Yang; Li, Wei; Zhang, Cong; Lin, Jia; Li, Xue-Nan; Li, Jing-Long

2017-04-01

Selenium (Se) incorporated in selenoproteins as selenocysteine and supports various important cellular and organismal functions. We recently reported that chicken brain exhibited high priority for Se supply and retention under conditions of dietary Se deficiency and supernutrition Li et al. (2012) . However, the selenotranscriptome expressions and their response to Se status in chicken central nervous system (CNS) are unclear. To better understand the relationship of Se homeostasis and selenoproteins expression in chicken CNS, 1day-old HyLine White chickens were fed a low Se diet (Se-L, 0.028mg/g) supplemented with 4 levels of dietary Se (0 to 5.0mgSe/kg) as Na 2 SeO 3 for 8weeks. Then chickens were dissected for getting the CNS, which included cerebral cortex, cerebellum, thalamus, bulbus cinereus and marrow. The expressions of selenoproteome which have 24 selenoproteins were detected by the quantitative real-time PCR array. The concept of a selenoprotein hierarchy was developed and the hierarchy of different regions in chicken CNS was existence, especially cerebral cortex and bulbus cinereus. The expression of selenoproteins has a hierarch while changing Se content, and Selenoprotein T (Selt), Selenoprotein K (Selk), Selenoprotein W (Selw), Selenoprotein U (Selu), Glutathione peroxidase 3 (Gpx3), Glutathione peroxidase 4 (Gpx4), Selenoprotein P (Sepp1), Selenoprotein O (Selo), Selenoprotein 15 (Sel15), Selenoprotein N (Seln), Glutathione peroxidase 2 (Gpx2) and Selenoprotein P 2 (Sepp2) take more necessary function in the chicken CNS. Therefore, we hypothesize that hierarchy of regulated the transcriptions of selenoproteome makes an important role of CNS Se metabolism and transport in birds. Copyright © 2017 Elsevier Inc. All rights reserved.

Alterations on the morphology, nitric oxide synthesis and activity of platelets reproduced in rats as possible biomarkers for depression are reversed by fluoxetine.

Science.gov (United States)

González-Trujano, María Eva; Alvarado-Vásquez, Noé; Mendoza-Sotelo, José; López, Guadalupe; Estrada-Camarena, Erika; Martínez-Mota, Lucia; Moreno, Julia

2012-08-01

Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Naïve rats were compared to those receiving vehicle or fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced. Copyright © 2012 Elsevier Inc. All rights reserved.

Vitamin E alters alveolar type II cell phospholipid synthesis in oxygen and air

International Nuclear Information System (INIS)

Kennedy, K.A.; Snyder, J.M.; Stenzel, W.; Saito, K.; Warshaw, J.B.

1990-01-01

Newborn rats were injected with vitamin E or placebo daily until 6 days after birth. The effect of vitamin E pretreatment on in vitro surfactant phospholipid synthesis was examined in isolated type II cells exposed to oxygen or air form 24 h in vitro. Type II cells were also isolated from untreated 6-day-old rats and cultured for 24 h in oxygen or air with control medium or vitamin E supplemented medium. These cells were used to examine the effect of vitamin E exposure in vitro on type II cell phospholipid synthesis and ultrastructure. Phosphatidylcholine (PC) synthesis was reduced in cells cultured in oxygen as compared with air. This decrease was not prevented by in vivo pretreatment or in vitro supplementation with vitamin E. Vitamin E pretreatment increased the ratio of disaturated PC to total PC and increased phosphatidylglycerol synthesis. The volume density of lamellar bodies in type II cells was increased in cells maintained in oxygen. Vitamin E did not affect the volume density of lamellar bodies. We conclude that in vitro hyperoxia inhibits alveolar type II cell phosphatidylcholine synthesis without decreasing lamellar body volume density and that supplemental vitamin E does not prevent hyperoxia-induced decrease in phosphatidylcholine synthesis

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

Energy Technology Data Exchange (ETDEWEB)

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng; Sarsour, Ehab H.; Goswami, Prabhat C., E-mail: prabhat-goswami@uiowa.edu

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays, were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.

Structural alterations in heart valves during left ventricular pressure overload in the rat

NARCIS (Netherlands)

Willems, I. E.; Havenith, M. G.; Smits, J. F.; Daemen, M. J.

1994-01-01

Heart valves are an important denominator of the function of the heart but detailed studies of structural alterations of heart valves after hemodynamic changes are lacking. Structural alterations of heart valves, including DNA synthesis, collagen mRNA, and protein concentration were measured in

A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse.

Science.gov (United States)

Wright, Craig Robert; Allsopp, Giselle Larissa; Addinsall, Alex Bernard; McRae, Natasha Lee; Andrikopoulos, Sofianos; Stupka, Nicole

2017-01-01

Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD). There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S ( Seps1 ) are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion ( mdx : Seps1 -/+ ) were generated. The mdx:Seps1 -/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL) muscles, mRNA expression of monocyte chemoattractant protein 1 ( Mcp-1 ) ( P = 0.034), macrophage marker F4/80 ( P = 0.030), and transforming growth factor-β1 ( Tgf-β1 ) ( P = 0.056) were increased in mdx:Seps1 -/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.

Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer

International Nuclear Information System (INIS)

Fernández-Vega, Iván; García, Olivia; Crespo, Ainara; Castañón, Sonia; Menéndez, Primitiva; Astudillo, Aurora; Quirós, Luis M

2013-01-01

The expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer. Twenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest. No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays anti-metastatic features

Sulphur depletion altered somatic embryogenesis in Theobroma ...

African Journals Online (AJOL)

USER

2010-08-30

Aug 30, 2010 ... embryo) occur in response to alteration of genes expression patterns ... the proteins synthesis and the rate with which all amino ... thiamine-HCl, 1 mgml-1 nicotinic acid and 2 mgml-1 glycine), 20 gL-1 ... Amino acids and soluble sugar extraction .... 0.1% (v/v) Triton X-100, 0.1 % (w/v) dithiothreitol, and 0.2%.

Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

Science.gov (United States)

Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

2016-06-01

Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse

Directory of Open Access Journals (Sweden)

Craig Robert Wright

2017-01-01

Full Text Available Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD. There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S (Seps1 are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion (mdx:Seps1−/+ were generated. The mdx:Seps1−/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL muscles, mRNA expression of monocyte chemoattractant protein 1 (Mcp-1 (P=0.034, macrophage marker F4/80 (P=0.030, and transforming growth factor-β1 (Tgf-β1 (P=0.056 were increased in mdx:Seps1−/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.

Distribution and reuse of 76Se-selenosugar in selenium-deficient rats

International Nuclear Information System (INIS)

Suzuki, Kazuo T.; Somekawa, Layla; Suzuki, Noriyuki

2006-01-01

Nutritional selenium compounds are transformed to the common intermediate selenide and then utilized for selenoprotein synthesis or excreted in urine mostly as 1β-methylseleno-N-acetyl-DD-galactosamine (selenosugar). Since the biological significance of selenosugar formation is unknown, we investigated their role in the formation of selenoenzymes in selenium deficiency. Rats were depleted of endogenous natural abundance selenium with a single stable isotope ( 82 Se) and then made Se-deficient. 76 Se-Selenosugar was administered intravenously to the rats and their urine, serum, liver, kidneys and testes were subjected to speciation analysis with HPLC inductively coupled argon plasma mass spectrometry. Most 76 Se was recovered in its intact form (approximately 80% of dose) in urine within 1 h. Speciation analysis revealed that residual endogenous natural abundance selenium estimated by 77 Se and 78 Se was negligible and distinct distributions of the labeled 76 Se were detected in the body fluids and organs without interference from the endogenous natural abundance stable isotope. Namely, intact 76 Se-selenosugar was distributed to organs after the injection, and 76 Se was used for selenoprotein synthesis. Oxidation to methylseleninic acid and/or hydrolysis of the selenoacetal group to methylselenol were proposed to the transformation of selenosugar for the reuse. Effective use of an enriched stable isotope as an absolute label in hosts depleted of natural abundance isotopes was discussed for application in tracer experiments

Study of nuclear glasses alteration gel and synthesis of some model gels

International Nuclear Information System (INIS)

Ricol, S.

1995-01-01

This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs

Collagen synthesis in CBA mouse heart after total thoracic irradiation

International Nuclear Information System (INIS)

Murray, J.C.; Parkins, C.S.; Institute of Cancer Research, Sutton

1988-01-01

CBA mice were irradiated to the whole thorax with single doses of 240 kVp X-rays in the dose range 8-16 Gy. Collagen and total protein synthesis rates in the heart were measured at 2-monthly intervals using a radio-isotope incorporation techniques. Doses of 10 Gy or greater caused a slight increase in collagen synthesis, followed by significantly reduced collagen synthesis by 16 weeks or longer after treatment. The depression in synthesis appeared correspondingly earlier with increasing dose. Total protein synthesis in heart followed similar patterns although changes were not statistically significant, indicating that the changes reflected alterations to collagen synthesis specifally, and not protein synthesis in geneal. Total hydroxyproline measurements showed no significant changes in heart collagen at any time as a result of X-irradiation. 18 refs.; 7 figs

Selenium. Role of the Essential Metalloid in Health

Science.gov (United States)

Kurokawa, Suguru; Berry, Marla J.

2015-01-01

Selenium is an essential micronutrient in mammals, but is also recognized as toxic in excess. It is a non-metal with properties that are intermediate between the chalcogen elements sulfur and tellurium. Selenium exerts its biological functions through selenoproteins. Selenoproteins contain selenium in the form of the 21st amino acid, selenocysteine (Sec), which is an analog of cysteine with the sulfur-containing side chain replaced by a Se-containing side chain. Sec is encoded by the codon UGA, which is one of three termination codons for mRNA translation in non-selenoprotein genes. Recognition of the UGA codon as a Sec insertion site instead of stop requires a Sec insertion sequence (SECIS) element in selenoprotein mRNAs and a unique selenocysteyl-tRNA, both of which are recognized by specialized protein factors. Unlike the 20 standard amino acids, Sec is biosynthesized from serine on its tRNA. Twenty-five selenoproteins are encoded in the human genome. Most of the selenoprotein genes were discovered by bioinformatics approaches, searching for SECIS elements downstream of in-frame UGA codons. Sec has been described as having stronger nucleophilic and electrophilic properties than cysteine, and Sec is present in the catalytic site of all selenoenzymes. Most selenoproteins, whose functions are known, are involved in redox systems and signaling pathways. However, several selenoproteins are not well characterized in terms of their function. The selenium field has grown dramatically in the last few decades, and research on selenium biology is providing extensive new information regarding its importance for human health. PMID:24470102

Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders.

Science.gov (United States)

di Giuseppe, Romina; Plachta-Danielzik, Sandra; Koch, Manja; Nöthlings, Ute; Schlesinger, Sabrina; Borggrefe, Jan; Both, Marcus; Müller, Hans-Peter; Kassubek, Jan; Jacobs, Gunnar; Lieb, Wolfgang

2018-02-14

The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease. In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits. Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits. Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents

Directory of Open Access Journals (Sweden)

Sunde Roger A

2011-01-01

Full Text Available Abstract Background Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1, are down-regulated dramatically by selenium (Se deficiency. These levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency. These levels, however, do not further increase with super-nutritional or toxic Se status, making them ineffective for detection of high Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial as well as adverse health outcomes. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with up to 5 μg Se/g diet. Results There was no effect of Se status on growth of mice fed 0 to 0.2 μg Se/g diet or rats fed 0 to 2 μg Se/g diet, but rats fed 5 μg Se/g diet showed a 23% decrease in growth and elevated plasma alanine aminotransferase activity, indicating Se toxicity. Rats fed 5 μg Se/g diet had significantly altered expression of 1193 liver transcripts, whereas mice or rats fed ≤ 2 μg Se/g diet had Conclusion This study shows that Se toxicity (5 μg Se/g diet in rats vastly alters the liver transcriptome whereas Se-deficiency or high but non-toxic Se intake elicits relatively few changes. This is the first evidence that a vastly expanded number of transcriptional changes itself can be a biomarker of Se toxicity, and that identified transcripts can be used to develop molecular biomarker panels that accurately predict super-nutritional and toxic Se status.

Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice*

Science.gov (United States)

Kasaikina, Marina V.; Fomenko, Dmitri E.; Labunskyy, Vyacheslav M.; Lachke, Salil A.; Qiu, Wenya; Moncaster, Juliet A.; Zhang, Jie; Wojnarowicz, Mark W.; Natarajan, Sathish Kumar; Malinouski, Mikalai; Schweizer, Ulrich; Tsuji, Petra A.; Carlson, Bradley A.; Maas, Richard L.; Lou, Marjorie F.; Goldstein, Lee E.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteine-rich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable and fertile, showed normal brain morphology, and did not activate endoplasmic reticulum stress pathways. However, parameters of oxidative stress were elevated in the livers of these mice. We found that Sep15 mRNA was enriched during lens development. Further phenotypic characterization of Sep15 KO mice revealed a prominent nuclear cataract that developed at an early age. These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation. We suggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency. PMID:21768092

Protein synthesis in x-irradiated rabbit lens

International Nuclear Information System (INIS)

Garadi, R.; Foltyn, A.R.; Giblin, F.J.; Reddy, V.N.

1984-01-01

The present study deals with the incorporation of 35 S methionine into lens crystallins as a function of time after x-irradiation. Crystallin synthesis is first affected approximately 4 weeks following x-irradiation. This coincides with the time period at which the ratio of the two cations in the lens is affected, as shown in earlier studies. A greater decrease in 35 S-methionine incorporation into crystallins is observed between 5-7 weeks following x-irradiation in good agreement with a cation imbalance at these time intervals. These studies also revealed for the first time that the change in cation distribution can affect not only crystallin synthesis, but also the synthesis of certain polypeptides of lens membranes. No alteration in protein synthesis could be detected in lens epithelium even after 7 weeks following irradiation. In addition to the effect of Na+ and K+ levels on protein synthesis, an impaired transport of amino acids into the x-rayed lens was also found to be a factor in the observed reduction in synthesis of the crystallin, cytoskeletal and membrane proteins of the fiber cells. It is concluded that Na+/K+ ratio as well as the availability of amino acids in the lens are important factors in protein synthesis of x-ray cataracts

Selenium Utilization Strategy by Microalgae

Directory of Open Access Journals (Sweden)

Hiroya Araie

2009-11-01

Full Text Available The diversity of selenoproteins raises the question of why so many life forms require selenium. Selenoproteins are found in bacteria, archaea, and many eukaryotes. In photosynthetic microorganisms, the essential requirement for selenium has been reported in 33 species belonging to six phyla, although its biochemical significance is still unclear. According to genome databases, 20 species are defined as selenoprotein-producing organisms, including five photosynthetic organisms. In a marine coccolithophorid, Emiliania huxleyi (Haptophyta, we recently found unique characteristics of selenium utilization and novel selenoproteins using 75Se-tracer experiments. In E. huxleyi, selenite, not selenate, is the main substrate used and its uptake is driven by an ATP-dependent highaffinity, active transport system. Selenite is immediately metabolized to low-molecular mass compounds and partly converted to at least six selenoproteins, named EhSEP1–6. The most (EhSEP2 and second-most abundant selenoproteins (EhSEP1 are disulfide isomerase (PDI homologous protein and thioredoxin reductase (TR 1, respectively. Involvement of selenium in PDI is unique in this organism, while TR1 is also found in other organisms. In this review, we summarize physiological, biochemical, and molecular aspects of selenium utilization by microalgae and discuss their strategy of selenium utilization.

Chronological protein synthesis in regenerating rat liver.

Science.gov (United States)

He, Jinjun; Hao, Shuai; Zhang, Hao; Guo, Fuzheng; Huang, Lingyun; Xiao, Xueyuan; He, Dacheng

2015-07-01

Liver regeneration has been studied for decades; however, its regulation remains unclear. In this study, we report a dynamic tracing of protein synthesis in rat regenerating liver with a new proteomic technique, (35) S in vivo labeling analysis for dynamic proteomics (SiLAD). Conventional proteomic techniques typically measure protein alteration in accumulated amounts. The SiLAD technique specifically detects protein synthesis velocity instead of accumulated amounts of protein through (35) S pulse labeling of newly synthesized proteins, providing a direct way for analyzing protein synthesis variations. Consequently, protein synthesis within short as 30 min was visualized and protein regulations in the first 8 h of regenerating liver were dynamically traced. Further, the 3.5-5 h post partial hepatectomy (PHx) was shown to be an important regulatory turning point by acute regulation of many proteins in the initiation of liver regeneration. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increase of placental sensitivity to melatonin and the alteration to its local synthesis in hypertensive syndromes in pregnancy.

Science.gov (United States)

Yamamoto, Douglas de Resende; Yamamoto, Leandro de Resende; Rocha, Laura Penna; Machado, Juliana Reis; Guimarães, Camila Souza de Oliveira; Reis, Marlene Antônia Dos; Corrêa, Rosana Rosa Miranda

2013-05-01

To evaluate the relation between hypertensive syndromes and melatonin, and its possible protective role against lesions due to hypertension. Placentas were classified into gestational hypertension (GH), chronic hypertension (CH), pre-eclampsia (PE) and pre-eclampsia superimposed on chronic hypertension, and morphologically examined by hematoxylin-eosin and periodic acid Schiff methods. Immunohistochemistry was performed to detect tryptophan hydroxylase (TH) and melatonin receptor 1A (MR-1A). MR-1A expression was higher in all types of hypertensive syndromes in pregnancy (HSP), mainly in cases with GH, in Caesarean section delivery, preterm placentas and in the cases with alterations in the placental morphology, particularly those presenting inflammation. The expression of TH was higher in cases with CH when compared with the control. This expression was lower in primigestas, in the cases of inflammation and with PE. HSP therapies should be considered and studied, especially in the cases of HSP associated with PE, in which the placenta is more sensitive as it has more receptors, but its synthesis ability is reduced. As for GH and CH, the possible benefits should be evaluated, since the local placental ability to produce melatonin still exists.

Type V Collagen is Persistently Altered after Inguinal Hernia Repair

DEFF Research Database (Denmark)

Lorentzen, L; Henriksen, N A; Juhl, P

2018-01-01

BACKGROUND AND AIMS: Hernia formation is associated with alterations of collagen metabolism. Collagen synthesis and degradation cause a systemic release of products, which are measurable in serum. Recently, we reported changes in type V and IV collagen metabolisms in patients with inguinal...... elective cholecystectomy served as controls (n = 10). Whole venous blood was collected 35-55 months after operation. Biomarkers for type V collagen synthesis (Pro-C5) and degradation (C5M) and those for type IV collagen synthesis (P4NP) and degradation (C4M2) were measured by a solid-phase competitive...... assay. RESULTS: The turnover of type V collagen (Pro-C5/C5M) was slightly higher postoperatively when compared to preoperatively in the inguinal hernia group (P = 0.034). In addition, the results revealed a postoperatively lower type V collagen turnover level in the inguinal hernia group compared...

Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells

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Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

2016-01-01

Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells. PMID:26943035

Metabolic engineering of the morphology of Aspergillus oryzae by altering chitin synthesis

DEFF Research Database (Denmark)

Muller, C.; Mcintyre, Mhairi; Hansen, Kim

2002-01-01

Morphology and alpha-amylase production during submerged cultivation were examined in a wild-type strain (A1560) and in strains of Aspergillus oryzae in which chitin synthase B (chsB) and chitin synthesis myosin A (csmA) have been disrupted (ChsB/G and CM101). In a flowthrough cell, the growth...

Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.

Science.gov (United States)

Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M

1996-06-01

The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following

Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture

Energy Technology Data Exchange (ETDEWEB)

Roeder, R.A.; Thorpe, S.D.; Byers, F.M.; Schelling, G.T.; Gunn, J.M.

Muscle cell culture (L/sub 6/) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effect of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 ..mu..M compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of (/sup 3/H) leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using (/sup 3/H) leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes by dexamethasone, but increased in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 ..mu..M level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle.

Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture

International Nuclear Information System (INIS)

Roeder, R.A.; Thorpe, S.D.; Byers, F.M.; Schelling, G.T.; Gunn, J.M.

1986-01-01

Muscle cell culture (L 6 ) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effect of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 μM compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of [ 3 H] leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using [ 3 H] leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes by dexamethasone, but increased in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 μM level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle

Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to triiodothyronine (T3) in chicken thyroids.

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Lin, Shi-lei; Wang, Cong-wu; Tan, Si-ran; Liang, Yang; Yao, Hai-dong; Zhang, Zi-wei; Xu, Shi-wen

2014-12-01

Selenium (Se) influences the metabolism of thyroid hormones in mammals. However, the role of Se deficiency in the regulation of thyroid hormones in chickens is not well known. In the present study, we examined the levels of thyroidal triiodothyronine (T3), thyroidal thyroxine (T4), free triiodothyronine, free thyroxine (FT4), and thyroid-stimulating hormone in the serum and the mRNA expression levels of 25 selenoproteins in chicken thyroids. Then, principal component analysis (PCA) was performed to analyze the relationships between the selenoproteins. The results indicated that Se deficiency influenced the conversion of T4 to T3 and induced the accumulation of T4 and FT4. In addition, the mRNA expression levels of the selenoproteins were generally decreased by Se deficiency. The PCA showed that eight selenoproteins (deiodinase 1 (Dio1), Dio2, Dio3, thioredoxin reductase 2 (Txnrd2), selenoprotein i (Seli), selenoprotein u (Selu), glutathione peroxidase 1 (Gpx1), and Gpx2) have similar trends, which indicated that they may play similar roles in the metabolism of thyroid hormones. The results showed that Se deficiency inhibited the conversion of T4 to T3 and decreased the levels of the crucial metabolic enzymes of the thyroid hormones, Dio1, Dio2, and Dio3, in chickens. In addition, the decreased selenoproteins (Dio1, Dio2, Dio3, Txnrd2, Seli, Selu, Gpx1, and Gpx2) induced by Se deficiency may indirectly limit the conversion of T4 to T3 in chicken thyroids. The information presented in this study is helpful to understand the role of Se in the thyroid function of chickens.

Response of rat brain protein synthesis to ethanol and sodium barbital

International Nuclear Information System (INIS)

Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

1987-01-01

Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14 C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the 14 C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14 C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units

Metabolic alterations during ascosporogenesis of Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Carvalho, Sandra; Nadkarni, G.B.

1977-01-01

Sporulation of S. cerevisiae has been shown to alter the profiles of enzymes involved in gluconeogenesis and glycolysis. The enhancement in the levels of total cellular carbohydrates could be correlated with the enhancement in fructose 1,6-diphosphatase and trehalose-phosphate synthetase. The latter activity could account for the 15-fold increase in trehalose levels in sporulating cells. Glucose-6-phosphatase, pyruvate kinase and phosphofructokinase showed continuous decline during ascosporogenesis. The relative incorporation of radioactivity from possible precursors of gluconeogenesis indicated that acetate-2- 14 C alone could contribute to carbohydrate synthesis. (author)

Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man

International Nuclear Information System (INIS)

Pooler, P.A.; Duane, W.C.

1988-01-01

In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from [26-14C]cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

Science.gov (United States)

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Altered erythropoiesis and iron metabolism in carriers of thalassemia

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Guimarães, Jacqueline S.; Cominal, Juçara G.; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z.; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

2014-01-01

The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis and dysfunctional iron metabolism have not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changings in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferrin and (hepcidin/ferritin)/sTfR are respectively increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis. PMID:25307880

Synthesis of Amino Acid Precursors with Organic Solids in Planetesimals with Liquid Water

Science.gov (United States)

Kebukawa, Y; Misawa, S.; Matsukuma, J.; Chan, Q. H. S.; Kobayashi, J.; Tachibana, S.; Zolensky, M. E.

2017-01-01

Amino acids are important ingredients of life that would have been delivered to Earth by extraterrestrial sources, e.g., comets and meteorites. Amino acids are found in aqueously altered carbonaceous chondrites in good part in the form of precursors that release amino acids after acid hydrolysis. Meanwhile, most of the organic carbon (greater than 70 weight %) in carbonaceous chondrites exists in the form of solvent insoluble organic matter (IOM) with complex macromolecular structures. Complex macromolecular organic matter can be produced by either photolysis of interstellar ices or aqueous chemistry in planetesimals. We focused on the synthesis of amino acids during aqueous alteration, and demonstrated one-pot synthesis of a complex suite of amino acids simultaneously with IOM via hydrothermal experiments simulating the aqueous processing

Inhibition of skeletal muscle protein synthesis in septic intra-abdominal abscess

International Nuclear Information System (INIS)

Vary, T.C.; Siegel, J.H.; Tall, B.D.; Morris, J.G.; Smith, J.A.

1988-01-01

Chronic sepsis is always associated with profound wasting leading to increased release of amino acids from skeletal muscle. Net protein catabolism may be due to decreased rate of synthesis, increased rate of degradation, or both. To determine whether protein synthesis is altered in chronic sepsis, the rate of protein synthesis in vivo was estimated by measuring the incorporation of [ 3 H]-phenylalanine in skeletal muscle protein in a chronic (5-day) septic rat model induced by creation of a stable intra-abdominal abscess using an E. coli + B. fragilis-infected sterile fecal-agar pellet as foreign body nidus. Septic rats failed to gain weight at rates similar to control animals, therefore control animals were weight matched to the septic animals. The skeletal muscle protein content in septic animals was significantly reduced relative to control animals (0.18 +/- 0.01 vs. 0.21 +/- 0.01 mg protein/gm wet wt; p less than 0.02). The rate of incorporation of [ 3 H]-phenylalanine into skeletal muscle protein from control animals was 39 +/- 4 nmole/gm wet wt/hr or a fractional synthetic rate of 5.2 +/- 0.5%/day. In contrast to control animals, the fractional synthetic rate in septic animals (2.6 +/- 0.2%/day) was reduced by 50% compared to control animals (p less than 0.005). The decreased rate of protein synthesis in sepsis was not due to an energy deficit, as high-energy phosphates and ATP/ADP ratio were not altered. This decrease in protein synthesis occurred even though septic animals consumed as much food as control animals

Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study.

Science.gov (United States)

Federige, Marco Aurélio Ferreira; Romaldini, João Hamilton; Miklos, Ana Beatriz Pinotti Pedro; Koike, Marcia Kiyomi; Takei, Kioko; Portes, Evandro de Souza

2017-12-01

Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 μg/L), GO: 53.6 (43.5-60.0 μg/L), HT: 51.9 (44.6-58.5 μg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 μg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 μg/mL) and in HT patients: 0.35 (0.2-1.17 μg/mL) compared to C group patients: 1.00 (0.564.21 μg/mL) as well as to GD patients: 1.19 (0.62-2.5 μg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Diet fat alters synaptosomal phosphatidylethanolaminemethyl-transferase activity and phosphatidylcholine synthesis in brain

International Nuclear Information System (INIS)

Hargreaves, K.M.; Clandinin, M.T.

1986-01-01

Phosphatidylcholine (PC) can be synthesized via three routes, each having potentially different metabolic fates. One route for PC synthesis is methylation of phosphatidylethanolamine (PE). To examine if dietary fat affects membrane PE composition and phosphatidylethanolaminemethyltransferase (PEMT) activity, male weanling rats were fed semi-purified diets containing 20% (w/w) fat of differing fatty acid composition for 24 days. Microsomal and synaptic plasma membranes were isolated and phospholipid composition analyzed. PEMT activity was measured by incorporation of the methyl group from 3 H-S-adenosylmethionine into PE. Polyunsaturated diets high in omega 6 fatty acids produce a high ratio of omega 6/omega 3 fatty acids in synaptic plasma membranes. Dietary omega 3 and omega 6 fatty acid levels are reflected in membrane phospholipid content of 22:6(3), 20:4(6), 22:4(6) and 22:5(6). Diet-induced increase in these longer chain homologues of omega 6 and omega 3 fatty acids and a high ratio of omega 6/omega 3 fatty acids in PE are both associated with increased PEMT activity. These results suggest that diet-fat induced change in fatty acid composition of membrane PE results in transition in PEMT activity and synthesis of PC in brain, by providing preferred species of PE for methylation

Intestinal mucosa in diabetes: synthesis of total proteins and sucrase-isomaltase

International Nuclear Information System (INIS)

Olsen, W.A.; Perchellet, E.; Malinowski, R.L.

1986-01-01

The effects of insulin deficiency on nitrogen metabolism in muscle and liver have been extensively studied with recent in vivo demonstration of impaired protein synthesis in rats with streptozotocin-induced diabetes. Despite the significant contribution of small intestinal mucosa to overall protein metabolism, the effect of insulin deficiency on intestinal protein synthesis have not been completely defined. The authors studied the effects of streptozotocin-induced diabetes on total protein synthesis by small intestinal mucosa and on synthesis of a single enzyme protein of the enterocyte brush-border membrane sucrase-isomaltase. They used the flood-dose technique to minimize the difficulties of measuring specific radioactivity of precursor phenylalanine and determined incorporation into mucosal proteins and sucrase-isomaltase 20 min after injection of the labeled amino acid. Diabetes did not alter mucosal mass as determined by weight and content of protein and DNA during the 5 days after injection of streptozotocin. Increased rates of sucrase-isomaltase synthesis developed beginning on day 3, and those of total protein developed on day 5. Thus intestinal mucosal protein synthesis is not an insulin-sensitive process

Elevated dolichol synthesis in mouse testes during spermatogenesis

International Nuclear Information System (INIS)

James, M.J.; Kandutsch, A.A.

1980-01-01

The synthesis in mouse testes of the isopremoid lipid dolichol, the phosphate esters of which are involved in glycoprotein assembly, was investigated. Because the pathways for dolichol and cholesterol branch from a common sequence of reactions, comparisons of the rates of synthesis of these two lipids can reveal specific alterations in the flow of metabolites along the branch leading to dolichol. Our results showed that the ratio of dolichol to sterol synthesis in testes was from 20- to 72-fold higher than any ratios we have measured in murine liver or cell cultures. In contrast, testes deficient in spermatogenic cells, from x-irradiated mice, or from mice with mutant W/Wv or at/at genotypes, synthesized normal amounts of cholesterol, but much less dolichol. Thus, the high rate of dolichol synthesis in normal testes appeared to be associated with one or more of the spermatogenic cell types. It was also observed that newly biosynthesized testicular dolichols are slightly more polar than the pig liver dolichols used as standards. Possible modifications of the dolichol structures that might account for the increased polarity are discussed

Altered hypothalamic protein expression in a rat model of Huntington's disease.

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Wei-na Cong

Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

Injury-induced inhibition of small intestinal protein and nucleic acid synthesis

International Nuclear Information System (INIS)

Carter, E.A.; Hatz, R.A.; Yarmush, M.L.; Tompkins, R.G.

1990-01-01

Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury

Interactions between fatty acid synthesis, oxidation, and esterification in the production of triglyceride-rich lipoproteins by the liver.

Science.gov (United States)

Fukuda, N; Ontko, J A

1984-08-01

In a series of experiments with male rat livers perfused with or without 5-tetradecyloxy-2-furoic acid (TOFA) in the presence and absence of oleate, the relationships between fatty acid synthesis, oxidation, and esterification from newly synthesized and exogenous fatty acid substrates have been examined. When livers from fed rats were perfused without exogenous fatty acid substrate, 20% of the triglyceride secreted was derived from de novo fatty acid synthesis. Addition of TOFA caused immediate and nearly complete inhibition of fatty acid synthesis, measured by incorporation of 3H2O into fatty acids. Concurrently, ketone body production increased 140% and triglyceride secretion decreased 84%. These marked reciprocal alterations in fatty acid synthesis and oxidation in the liver almost completely abolished the production of very low density lipoproteins (VLDL). Cholesterol synthesis was also depressed by TOFA, suggesting that this drug also inhibited lipid synthesis at a site other than acetyl-CoA carboxylase. When livers from fed rats were supplied with a continuous infusion of [1-14C]oleate as exogenous substrate, similar proportions, about 45-47%, of both ketone bodies and triglyceride in the perfusate were derived from the infused [1-14C]oleate. The production of ketone bodies was markedly increased by TOFA; the secretion of triglyceride and cholesterol were decreased. Altered conversion of [1-14C]oleate into these products occurred in parallel. While TOFA decreased esterification of oleate into triglyceride, incorporation of [1-14C]oleate into liver phospholipid was increased, indicating that TOFA also affected glycerolipid synthesis at the stage of diglyceride processing. The decreased secretion of triglyceride and cholesterol following TOFA treatment was localized almost exclusively in VLDL. The specific activities of 3H and of 14C fatty acids in triglyceride of the perfusate were greater than those of liver triglyceride, indicating preferential secretion of

Hyperthermia-induced alteration of yeast susceptibility to mutation

International Nuclear Information System (INIS)

Mitchel, R.E.J.; Morrison, D.P.

1985-01-01

Diploid yeast (s. cerevisiae) were examined for alterations in susceptibility to induced mutation following hyperthermia treatment. In cells grown at 23 0 C, a non-lethal heat exposure (38 0 C, 30 min) markedly suppressed mutation induced by a subsequent non-killing dose of MNNG of MNU. Mutation by ENU, 8-MOP + UVA, or γ-rays was not affected. An intermediate level of mutation suppression was observed for mutation by 254nm UV or MMS. Mutation by MNNG was not suppressed by the same heat treatment delivered after the mutagen exposure. In a split dose experiment (two MNNG treatments separated by a heat exposure) no suppression of mutation was observed. Treatment with cycloheximide mimicked the effect of heat treatment. These data suggest that mutation induction by MNNG or MNU is protein synthesis dependent, i.e. an error-prone repair system is induced by exposure to MNNG or MNU but not by ENU, 8-MOP+UVA or γ-irradiation. We propose that hyperthermia treatment, by inducing stress protein synthesis at the expense of normal protein synthesis, precludes induction of this error-prone system. Therefore, in heat treated cells, DNA lesions produced by MNNG or MNU exposure must be resolved by an essentially constitutive system which is less error-prone than the inducible one

L-Proline, GABA Synthesis and Gamma Oscillations in Schizophrenia

OpenAIRE

Volk, David W.; Gonzalez-Burgos, Guillermo; Lewis, David A.

2016-01-01

Altered inhibition from parvalbumin-containing GABA neurons is thought to contribute to impaired gamma frequency oscillations and cognitive deficits in schizophrenia. Crabtree and colleagues report that proline dehydrogenase deficits produce excessive cytosolic levels of the GABA-mimetic L-proline which impairs GABA synthesis and gamma oscillations in a manner that mimics schizophrenia.

Synthesis of mordenite in geothermal wells

Energy Technology Data Exchange (ETDEWEB)

Konoya, M [Geological Survey of Hokkaido, Japan

1970-03-01

A study of the possible synthesis of mordenite in geothermal wells was conducted. In 1966 as part of a series of exploratory geothermal investigations, a 500 m well was drilled which had a temperature at 250 m of 120/sup 0/C. The well has constant temperature and constant pressure and has been used to study alteration. Specimens which were placed in the well were tested for mordenite. Mordenite was synthesized when Benki clay and a 10% KOH solution were placed in a Teflon tube at 250 m (120/sup 0/C and 22.3 kg/cm/sup 2/) for three months. No mordenite was synthesized when obsidian powder was used. These results indicate the possibility of synthesis of zeolite and clay minerals in geothermal wells. Two figures and four tables are provided.

Imaging of Selenium by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in 2-D Electrophoresis Gels and Biological Tissues.

Science.gov (United States)

Cruz, Elisa Castañeda Santa; Susanne Becker, J; Sabine Becker, J; Sussulini, Alessandra

2018-01-01

Selenium and selenoproteins are important components of living organisms that play a role in different biological processes. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful analytical technique that has been employed to obtain distribution maps of selenium in biological tissues in a direct manner, as well as in selenoproteins, previously separated by their molecular masses and isoelectric points using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In this chapter, we present the protocols to perform LA-ICP-MS imaging experiments, allowing the distribution visualization and determination of selenium and/or selenoproteins in biological systems.

Field Usage of Alternative Deicers for Snow and Ice Control : Transportation Research Synthesis.

Science.gov (United States)

2017-09-01

This Transportation Research Synthesis (TRS) summarizes non-chloride based deicers available on the market at this time, including acetate, formate, glycol, and succinate based deicing products. This report explores their feasibility for use as alter...

Study of nuclear glasses alteration gel and synthesis of some model gels; Etude du gel d`alteration des verres nucleaires et synthese de gels modeles

Energy Technology Data Exchange (ETDEWEB)

Ricol, S

1995-10-05

This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs.

Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases

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Anna Velia Stazi

2010-12-01

Full Text Available In celiac disease (CD, for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines and exogenous (environment, nutritional deficiency factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15 is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.

Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain

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Natalia Malek

2014-01-01

Full Text Available Endocannabinoids (EC, particularly anandamide (AEA, released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI. All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development.

Computer Aided Synthesis of a Four-Bar Mechanism For Soil Tilling ...

African Journals Online (AJOL)

points, circle points, lengths, and the coupler point of interest of the chosen mechanism were altered and the resulting coupler curve plotted. The process was repeated until a suitable coupler curve and acceptable dimensions and fixed points locations were obtained. Keywords: Computer synthesis, four-bar mechanism, ...

Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal or sepsis-induced changes in skeletal muscle protein synthesis in male or female mice.

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Steiner, Jennifer L; Pruznak, Anne M; Deiter, Gina; Navaratnarajah, Maithili; Kutzler, Lydia; Kimball, Scot R; Lang, Charles H

2014-01-01

Sepsis decreases skeletal muscle protein synthesis in part by impairing mTOR activity and the subsequent phosphorylation of 4E-BP1 and S6K1 thereby controlling translation initiation; however, the relative importance of changes in these two downstream substrates is unknown. The role of 4E-BP1 (and -BP2) in regulating muscle protein synthesis was assessed in wild-type (WT) and 4E-BP1/BP2 double knockout (DKO) male mice under basal conditions and in response to sepsis. At 12 months of age, body weight, lean body mass and energy expenditure did not differ between WT and DKO mice. Moreover, in vivo rates of protein synthesis in gastrocnemius, heart and liver did not differ between DKO and WT mice. Sepsis decreased skeletal muscle protein synthesis and S6K1 phosphorylation in WT and DKO male mice to a similar extent. Sepsis only decreased 4E-BP1 phosphorylation in WT mice as no 4E-BP1/BP2 protein was detected in muscle from DKO mice. Sepsis decreased the binding of eIF4G to eIF4E in WT mice; however, eIF4E•eIF4G binding was not altered in DKO mice under either basal or septic conditions. A comparable sepsis-induced increase in eIF4B phosphorylation was seen in both WT and DKO mice. eEF2 phosphorylation was similarly increased in muscle from WT septic mice and both control and septic DKO mice, compared to WT control values. The sepsis-induced increase in muscle MuRF1 and atrogin-1 (markers of proteolysis) as well as TNFα and IL-6 (inflammatory cytokines) mRNA was greater in DKO than WT mice. The sepsis-induced decrease in myocardial and hepatic protein synthesis did not differ between WT and DKO mice. These data suggest overall basal protein balance and synthesis is maintained in muscle of mice lacking both 4E-BP1/BP2 and that sepsis-induced changes in mTOR signaling may be mediated by a down-stream mechanism independent of 4E-BP1 phosphorylation and eIF4E•eIF4G binding.

Automated Controller Synthesis for non-Deterministic Piecewise-Affine Hybrid Systems

DEFF Research Database (Denmark)

Grunnet, Jacob Deleuran

formations. This thesis uses a hybrid systems model of a satellite formation with possible actuator faults as a motivating example for developing an automated control synthesis method for non-deterministic piecewise-affine hybrid systems (PAHS). The method does not only open an avenue for further research...... in fault tolerant satellite formation control, but can be used to synthesise controllers for a wide range of systems where external events can alter the system dynamics. The synthesis method relies on abstracting the hybrid system into a discrete game, finding a winning strategy for the game meeting...... game and linear optimisation solvers for controller refinement. To illustrate the efficacy of the method a reoccurring satellite formation example including actuator faults has been used. The end result is the application of PAHSCTRL on the example showing synthesis and simulation of a fault tolerant...

Defects in rhizobial cyclic glucan and lipopolysaccharide synthesis alter legume gene expression during nodule development

DEFF Research Database (Denmark)

D'Antuono, Alejandra L; Ott, Thomas; Krusell, Lene

2008-01-01

cDNA array technology was used to compare transcriptome profiles of Lotus japonicus roots inoculated with a Mesorhizobium loti wild-type and two mutant strains affected in cyclic beta(1-2) glucan synthesis (cgs) and in lipopolysaccharide synthesis (lpsbeta2). Expression of genes associated...... with the development of a fully functional nodule was significantly affected in plants inoculated with the cgs mutant. Array results also revealed that induction of marker genes for nodule development was delayed when plants were inoculated with the lpsbeta2 mutant. Quantitative real-time reverse......-transcriptase polymerase chain reaction was used to quantify gene expression of a subset of genes involved in plant defense response, redox metabolism, or genes that encode for nodulins. The majority of the genes analyzed in this study were more highly expressed in roots inoculated with the wild type compared with those...

l-Proline, GABA Synthesis and Gamma Oscillations in Schizophrenia.

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Volk, David W; Gonzalez-Burgos, Guillermo; Lewis, David A

2016-12-01

Altered inhibition from parvalbumin-containing GABA neurons is thought to contribute to impaired gamma frequency oscillations and cognitive deficits in schizophrenia. Crabtree and colleagues report that proline dehydrogenase deficits produce excessive cytosolic levels of the GABA-mimetic l-proline which impairs GABA synthesis and gamma oscillations in a manner that mimics schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Burn-induced stimulation of lysosomal enzyme synthesis in skeletal muscle

International Nuclear Information System (INIS)

Odessey, R.

1986-01-01

A localized burn injury to a rat hindlimb results in atrophy of soleus muscle (in the absence of cellular damage) which is attributable to an increase in muscle protein breakdown. Previous work has shown that lysosomal enzyme activities (cathepsins B, H, L, and D) are elevated in muscle from the burned leg by 50% to 100%. There is no change in endogenous neutral protease activity (+/- Ca ++ ). The increase in protease activity can not be attributed to changes in endogenous protease inhibitors. The latency [(Triton X100 treated - control)/triton treated] of lysosomal enzymes is approximately 50% and is not altered by burn injury. The rate of sucrose uptake is also not altered by burn. These experiments suggest that the rate of substrate supply to the lysosomal apparatus via endocytosis or autophagocytosis is not altered by burn. When muscles are preincubated with 3 H-phenylalanine or 3 H-mannose burn increased incorporation into protein of the fraction containing lysosomes by 100%. Preincubation in the presence of tunicamycin (an inhibitor of glycoprotein synthesis) inhibited incorporation of both labels into a microsomal fraction of the muscle from the burned leg, but has little effect on incorporation in the control muscle. These findings are consistent with the hypothesis that the burn-induced increase in protein breakdown is caused by an increase in lysosomal protease synthesis

Changes in isoprenoid lipid synthesis by gemfibrozil and clofibric acid in rat hepatocytes.

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Hashimoto, F; Taira, S; Hayashi, H

2000-05-15

We studied whether gemfibrozil and clofibric acid alter isoprenoid lipid synthesis in rat hepatocytes. After incubation of the cells with the agent for 74 hr, [(14)C]acetate or [(3)H]mevalonate was added, and the cells were further incubated for 4 hr. Gemfibrozil and clofibric acid increased ubiquinone synthesis from [(14)C]acetate and [(3)H]mevalonate. The effect of gemfibrozil was greater than that of clofibric acid. Also, gemfibrozil decreased dolichol synthesis from [(14)C]acetate and [(3)H]mevalonate. However, clofibric acid increased dolichol synthesis from [(3)H]mevalonate. Gemfibrozil decreased cholesterol synthesis from [(14)C]acetate and [(3)H]mevalonate. Clofibric acid decreased cholesterol synthesis from [(14)C]acetate, but did not affect synthesis from [(3)H]mevalonate. These results suggest that both agents, at different rates, activate the synthetic pathway of ubiquinone, at least from mevalonate. Gemfibrozil may inhibit the synthetic pathway of dolichol, at least from mevalonate. Contrary to gemfibrozil, clofibric acid may activate the synthetic pathway of dolichol from mevalonate. Gemfibrozil may inhibit the synthetic pathway of cholesterol from mevalonate in addition to the pathway from acetate to mevalonate inhibited by both agents.

Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

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Máthé, Csaba; M-Hamvas, Márta; Vasas, Gábor

2013-01-01

Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs), a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs) are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS) and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization. PMID:24084787

Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

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Gábor Vasas

2013-09-01

Full Text Available Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs, a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN, an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization.

Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

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Katharine A. Horzmann

2016-08-01

Full Text Available Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed.

A Propensity for n-omega-Amino Acids in Thermally-Altered Antarctic Meteorites

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Burton, Aaron S.; Elsila, Jamie E.; Callahan, Michael P.; Martin, Mildred G.; Glavin, Daniel P.; Johnson, Natasha M.; Dworkin, Jason P.

2012-01-01

Carbonaceous meteorites are known to contain a wealth of indigenous organic molecules, including amino acids, which suggests that these meteorites could have been an important source of prebiotic organic material during the origins of life on Earth and possibly elsewhere. We report the detection of extraterrestrial amino acids in thermally-altered type 3 CV and CO carbonaceous chondrites and ureilites recovered from Antarctica. The amino acid concentrations of the thirteen Antarctic meteorites were generally less abundant than in more amino acid-rich CI, CM, and CR carbonaceous chondrites that experienced much lower temperature aqueous alteration on their parent bodies. In contrast to low-temperature aqueously-altered meteorites that show complete structural diversity in amino acids formed predominantly by Strecker-cyanohydrin synthesis, the thermally-altered meteorites studied here are dominated by small, straight-chain, amine terminal (n-omega-amino) amino acids that are not consistent with Strecker formation. The carbon isotopic ratios of two extraterrestrial n-omega-amino acids measured in one of the CV chondrites are consistent with C-13-depletions observed previously in hydrocarbons produced by Fischer-Tropsch type reactions. The predominance of n-omega-amino acid isomers in thermally-altered meteorites hints at cosmochemical mechanisms for the preferential formation and preservation of a small subset of the possible amino acids.

Synthesis of hydroxylated sterols in transgenic Arabidopsis plants alters growth and steroid metabolism.

Science.gov (United States)

Beste, Lisa; Nahar, Nurun; Dalman, Kerstin; Fujioka, Shozo; Jonsson, Lisbeth; Dutta, Paresh C; Sitbon, Folke

2011-09-01

To explore mechanisms in plant sterol homeostasis, we have here increased the turnover of sterols in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum) plants by overexpressing four mouse cDNA encoding cholesterol hydroxylases (CHs), hydroxylating cholesterol at the C-7, C-24, C-25, or C-27 positions. Compared to the wild type, the four types of Arabidopsis transformant showed varying degrees of phenotypic alteration, the strongest one being in CH25 lines, which were dark-green dwarfs resembling brassinosteroid-related mutants. Gas chromatography-mass spectrometry analysis of extracts from wild-type Arabidopsis plants revealed trace levels of α and β forms of 7-hydroxycholesterol, 7-hydroxycampesterol, and 7-hydroxysitosterol. The expected hydroxycholesterol metabolites in CH7-, CH24-, and CH25 transformants were identified and quantified using gas chromatography-mass spectrometry. Additional hydroxysterol forms were also observed, particularly in CH25 plants. In CH24 and CH25 lines, but not in CH7 ones, the presence of hydroxysterols was correlated with a considerable alteration of the sterol profile and an increased sterol methyltransferase activity in microsomes. Moreover, CH25 lines contained clearly reduced levels of brassinosteroids, and displayed an enhanced drought tolerance. Equivalent transformations of potato plants with the CH25 construct increased hydroxysterol levels, but without the concomitant alteration of growth and sterol profiles observed in Arabidopsis. The results suggest that an increased hydroxylation of cholesterol and/or other sterols in Arabidopsis triggers compensatory processes, acting to maintain sterols at adequate levels.

Direct investigations of the immobilization of radionuclides in the alteration phases of spent nuclear fuel. 1998 annual progress report

International Nuclear Information System (INIS)

Burns, P.C.; Finch, R.J.

1998-01-01

'In an oxidizing environment, such as in the proposed repository at Yucca Mountain, rapid alteration rates are expected for spent nuclear fuel. Lab.-scale simulations have repeatedly shown that the dominant alteration products under repository conditions will be uranyl phases. There is an inadequate database that relates to the effects of the alteration products on the release of radionuclides, but this information is essential to provide a radionuclide release estimate. It is likely that many of the radionuclides contained in the fuel will be incorporated into the alteration products that form, potentially with a profound impact on the future mobility of radionuclides in the repository. The authors objective is to characterize the incorporation of radionuclides into alteration products by synthesis of uranyl phases doped with radionuclides, appropriate surrogate elements, or non-radioactive isotopes, followed by detailed phase characterization by diffraction and spectroscopic techniques. The research will permit a more realistic estimate of the release rates of the radionuclides from the near-field environment. This report summarizes work after 8 months of a 3-year project. The objective of investigating radionuclide incorporation in uranyl phases has required the development of synthesis techniques for various uranyl phases that are expected to form under repository conditions. The authors have synthesized and determined the structures of several uranyl phases that are new to science and that may be important alteration products under repository conditions. They have also undertaken the determination and refinement of the crystal structures of various uranyl phases that are likely to form under repository conditions. Other experiments include the investigation of the ion-exchange properties of uranyl phases under repository conditions.'

Selenium, but not lycopene or vitamin E, decreases growth of transplantable dunning R3327-H rat prostate tumors.

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Brian L Lindshield

Full Text Available BACKGROUND: Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by men diagnosed with prostate cancer. However, it is not clear whether consumption of these compounds, alone or in combination, results in improved outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the effects of dietary lycopene (250 mg/kg diet, selenium (methylselenocysteine, 1 mg/kg diet, and vitamin E (gamma-tocopherol, 200 mg/kg diet alone and in combination on the growth of androgen-dependent Dunning R3327-H rat prostate adenocarcinomas in male, Copenhagen rats. AIN-93G diets containing these micronutrients were prefed for 4 to 6 weeks prior to tumor implantation by subcutaneous injection. Tumors were allowed to grow for approximately 18 weeks. Across diet groups, methylselenocysteine consumption decreased final tumor area (P = 0.003, tumor weight (P = 0.003, and the tumor weight/body weight ratio (P = 0.003, but lycopene and gamma-tocopherol consumption intake did not alter any of these measures. There were no significant interactions among nutrient combinations on tumor growth. Methylselenocysteine consumption also led to small, but significant decreases in body weight (P = 0.007, food intake (P = 0.012, and body weight gain/food intake ratio (P = 0.022. However, neither body weight nor gain/food intake ratio was correlated with tumor weight. Methylselenocysteine, lycopene, and gamma-tocopherol consumed alone and in combination did not alter serum testosterone or dihydrotestosterone concentrations; tumor proliferation or apoptosis rates. In addition, the diets also did not alter tumor or prostate androgen receptor, probasin, selenoprotein 15, selenoprotein P, or selenium binding protein 2 mRNA expression. However, using castration and finasteride-treated tissues from a previous study, we found that androgen ablation altered expression of these selenium-associated proteins. CONCLUSIONS: Of the three micronutrients tested, only

Association of expression of selenoprotein P in mRNA and protein levels with metabolic syndrome in subjects with cardiovascular disease: Results of the Selenegene study.

Science.gov (United States)

Gharipour, Mojgan; Sadeghi, Masoumeh; Salehi, Mansour; Behmanesh, Mehrdad; Khosravi, Elham; Dianatkhah, Minoo; Haghjoo Javanmard, Shaghayegh; Razavi, Rouzbeh; Gharipour, Amin

2017-03-01

Selenoprotein P (SeP) is involved in transporting selenium from the liver to target tissues. Because SeP confers protection against disease by reducing chronic oxidative stress, the present study aimed to assess the level of SeP in the serum of patients with metabolic syndrome (MetS) with a history of cardiovascular disease (CVD). A cross-sectional study was conducted in 63 and 71 subjects with and without MetS in the presence of documented CVD. All demographic, anthropometric and cardiometabolic variables (lipids, blood glucose, blood pressure) were assessed. Lifestyle-related factors and personal history and familial CVD risk factors were recorded. The expression of SELP in mRNA and protein levels in the serum was measured, and MetS was determined using ATPIII criteria. Binary logistic regression analysis demonstrated MetS and SeP to be dependent and independent variables, respectively. Mean of systolic and diastolic blood pressure, triglyceride, high-density lipoprotein-cholesterol, fasting blood sugar, body mass index and waist circumference were higher among subjects with MetS (p = 0.05). The mean of selenium was higher among subjects with MetS, whereas the mean of SeP was lower among subjects with MetS (p family history, smoking status and nutrition. SeP and waist circumference show a significant relationship (OR =0.995; 95% CI = 0.990-1.00) (p < 0.033). We have demonstrated a significant decrease in circulating SeP levels according to MetS status in patients with documented cardiovascular disease. Copyright © 2017 John Wiley & Sons, Ltd.

Altered regulation of lipid biosynthesis in a mutant of Arabidopsis deficient in chloroplast glycerol-3-phosphate acyltransferase activity

International Nuclear Information System (INIS)

Kunst, L.; Browse, J.; Somerville, C.

1988-01-01

The leaf membrane lipids of many plant species, including Arabidopsis thaliana (L.) Heynh., are synthesized by two complementary pathways that are associated with the chloroplast and the endoplasmic reticulum. By screening directly for alterations in lipid acyl-group composition, the authors have identified several mutants of Arabidopsis that lack the plastid pathway because of a deficiency in activity of the first enzyme in the plastid pathway of glycerolipid synthesis, acyl-ACP:sn-glycerol-3-phosphate acyltransferase. The lesion results in an increased synthesis of lipids by the cytoplasmic pathway that largely compensates for the loss of the plastid pathway and provides nearly normal amounts of all the lipids required for chloroplast biogenesis. However, the fatty acid composition of the leaf membrane lipids of the mutants is altered because the acyltransferases associated with the two pathways normally exhibit different substrate specificities. The remarkable flexibility of the system provides an insight into the nature of the regulatory mechanisms that allocate lipids for membrane biogenesis

Extracellular calcium alters the effects of retinoic acid on DNA synthesis in cultured murine keratinocytes

International Nuclear Information System (INIS)

Tong, P.; Mayes, D.; Wheeler, L.

1986-01-01

The rate of proliferation of epidermal keratinocytes was manipulated by growing the cells in medium containing high or low concentrations of calcium. Keratinocytes cultured in high extracellular Ca ++ (1.4 mM and 2.8 mM) proliferated twice as fast as those grown in low Ca ++ medium (0.09 mM) as measured by incorporation of [ 3 H] thymidine into DNA. Exposure of high calcium keratinocytes to all-trans retinoic acid for 4 days caused a dose-related inhibition of DNA synthesis with an IC 50 of about 10 μM. In contrast, incubating low calcium keratinocytes with all-trans retinoic acid caused a dose-related stimulation of DNA synthesis with maximum increase of 278% over control at 10 μM. This increase was accompanied by increases in culture confluency with maximum increase of 109% in cell number of control at 10 μM. These results are of importance since they suggest Ca ++ may influence the effect of retinoids on keratinocytes

Undersulfation of proteoglycans and proteins alter C6 glioma cells proliferation, adhesion and extracellular matrix organization.

Science.gov (United States)

Mendes de Aguiar, Claudia B N; Garcez, Ricardo Castilho; Alvarez-Silva, Marcio; Trentin, Andréa Gonçalves

2002-11-01

Proteoglycans are considered to be important molecule in cell-microenvironment interactions. They are overexpressed in neoplastic cells modifying their growth and migration in hosts. In this work we verified that undersulfation of proteoglycans and other sulfated molecules, induced by sodium chlorate treatment, inhibited C6 glioma cells proliferation in a dose-dependent way. This effect was restored by the addition of exogenous heparin. We could not detect significant cell mortality in our culture condition. The treatment also impaired in a dose-dependent manner, C6 cell adhesion to extracellular matrix (ECM) proteins (collagen IV, laminin and fibronectin). In addition, sodium chlorate treatment altered C6 glioma cell morphology, from the fibroblast-like to a more rounded one. This effect was accompanied by increased synthesis of fibronectin and alterations in its extracellular network organization. However, we could not observe modifications on laminin organization and synthesis. The results suggest an important connection between sulfation degree with important tumor functions, such as proliferation and adhesion. We suggest that proteoglycans may modulate the glioma microenvironment network during tumor cell progression and invasion.

The synthesis of phosphatidylalcohols in HL-60 cells

International Nuclear Information System (INIS)

Tettenborn, C.S.

1988-01-01

This study focuses upon the phenomenon that 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates a pathway for the synthesis of phosphatidylalcohols in HL-60 cells during the differentiation of these cells to macrophages. Using exogenous ethanol as a substrate for this pathway, the synthesis of phosphatidylethanol is induced by TPA well before full expression of differentiation. Experiments done in whole cell cultures demonstrated that this pathway could utilize a wide range of other alcohols as substrates, including glycerol, a potential endogenous substrate. Using radiolabeling and iodine-staining as criteria, this TPA-inducible pathway was shown to result in a dramatic alteration of phospholipid composition, depending on the availability of the alcohol headgroup. A cell-free system was developed to explore the enzymatic reactions involved in phosphatidylalcohol synthesis, a main goal of these studies. For this purpose, the lipid pools of HL-60 cells were prelabeled with [ 3 H]arachidonic acid in the absence of ethanol and total cell homogenates were prepared by sonication. The ability of the cell lysates to synthesize phosphatidylethanol was assayed after addition of ethanol to the system

Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.

Science.gov (United States)

Crowell, Kristen T; Kelleher, Shannon L; Soybel, David I; Lang, Charles H

2016-11-01

Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc-adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post-CLP Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E-BP1. Acutely, sepsis increased TNF-α and IL-6 mRNA in muscle, and the increase in TNF-α was significantly greater in ZM mice. However, muscle protein synthesis and 4E-BP1 phosphorylation returned to baseline 5 days post-CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF-α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

Science.gov (United States)

He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

2012-07-01

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

Ecohydrologic impacts of rangeland fire on runoff and erosion: A literature synthesis

Science.gov (United States)

Frederick B. Pierson; C. Jason Williams

2016-01-01

Fire can dramatically influence rangeland hydrology and erosion by altering ecohydrologic relationships. This synthesis presents an ecohydrologic perspective on the effects of fire on rangeland runoff and erosion through a review of scientific literature spanning many decades. The objectives are: (1) to introduce rangeland hydrology and erosion concepts necessary for...

Uncoupled regulation of fibronectin and collagen synthesis in Rous sarcoma virus transformed avian tendon cells

International Nuclear Information System (INIS)

Parry, G.; Soo, W.J.; Bissell, M.J.

1979-01-01

The regulation of fibronectin and procollagen synthesis has been investigated in normal and Rous sarcoma virus transformed primary avian tendon cells. These two proteins interact at the cell periphery and both are reportedly lost upon transformation. Whether their synthesis was coordinately regulated in Rous sarcoma virus-infected cells was thus examined. It was found that while the synthesis of both pro α 1 and pro α 2 peptides was reduced upon transformation, the synthesis of fibronectin was not altered. Nevertheless, long term radiolabeling demonstrated that fibronectin levels were reduced in transformed cells. It is concluded that the reduction in levels of these components at the surface is brought about by different mechanisms; collagen levels being regulated by procollagen synthesis and fibronectin levels by degradation and/or release into the culture medium. The possibility is discussed that fibronectin is lost from the cell periphery of primary avian tendon cells as a consequence of decreased levels of anchoring collagen molecules

Organ-Specific Alterations in Fatty Acid De Novo Synthesis and Desaturation in a Rat Model of Programmed Obesity

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Desai Mina

2011-05-01

Full Text Available Abstract Background Small for gestational age (SGA leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR, catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity (SCD1 and rates of de novo fatty acid synthesis in young FR and Control offspring tissues at the end of the nursing period, as possible contributors to catch-up growth. Methods From gestational day 10 to term, dams fed ad libitum (Control or were 50% food-restricted to produce small FR pups. Control dams nursed all pups. At postnatal day 1 (p1 and p21, offspring body tissues were analyzed by GC/MS, and desaturation indices of palmitoleate/palmitate and oleate/stearate were calculated. SCD1 gene expression was determined by real-time PCR on adipose and liver. Offspring were enriched with deuterium that was given to dams in drinking water during lactation and de novo synthesis of offspring body tissues was determined at p21. Primary adipocyte cell cultures were established at p21 and exposed to U13C-glucose. Results FR offspring exhibited higher desaturation index in p1 and p21 adipose tissue, but decreased desaturation index in liver at p21. SCD1 gene expression at p21 was correspondingly increased in adipose and decreased in liver. FR subcutaneous fat demonstrated increased de novo synthesis at p21. Primary cell cultures exhibited increased de novo synthesis in FR. Conclusions Adipose tissue is the first site to exhibit increased de novo synthesis and desaturase activity in FR. Therefore, abnormal lipogenesis is already present prior to onset of obesity during the period of catch-up growth. These abnormalities may contribute to future obesity development.

Post ischemic reperfusion and anoxic perfusion in the isolated heart: alteration in distribution of radionuclides and in protein synthesis

Energy Technology Data Exchange (ETDEWEB)

Schreiber, S S; Oratz, M; Rothschild, M A [Veterans Administration Hospital, New York (USA)

1980-12-01

Reperfusion after ischemia and perfusion with total anoxia were studied in the isolated guinea pig heart model, Deprivation of oxygen in both situations resulted in a marked shift of circulation from the left to the right ventricle, with markedly increased spaces of distribution of sup(99m)Tc radionuclides and albumin in the latter. In view of the complexities of measuring protein synthesis during ischemia, continuous anoxic perfusion was used to evaluate this parameter in anoxic induced arrest. There was a profound fall in protein synthesis associated with this arrest, accompanied by a fall in ATP, creatine phosphate, glycogen, potassium, and a rise in lactate production. The fall in protein synthesis was more marked in the left ventricle. The changes in synthesis were almost completely prevented by initiating cardiac arrest with high K/sup +/ (16 meq/l) at the same time as anoxia; energy metabolism remained near normal, and recovery of contractility was nearly complete. The studies demonstrated the differences in vascular distribution between the ventricles after ischemia or with perfusion anoxia, the possible difference in availability of substrate to the two ventricles under these conditions, as well as the difference in protein synthetic response, and further support the protective effect of potassium induced arrest on the hypoxic heart.

Allergen-Induced Dermatitis Causes Alterations in Cutaneous Retinoid-Mediated Signaling in Mice

Science.gov (United States)

Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

2013-01-01

Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases. PMID:23977003

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

Science.gov (United States)

Smith, S J; Cases, S; Jensen, D R; Chen, H C; Sande, E; Tow, B; Sanan, D A; Raber, J; Eckel, R H; Farese, R V

2000-05-01

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character

International Nuclear Information System (INIS)

Fernández-Vega, Iván; García-Suárez, Olivia; García, Beatriz; Crespo, Ainara; Astudillo, Aurora; Quirós, Luis M.

2015-01-01

Heparan sulfate proteoglycans (HSPGs) are complex molecules involved in the growth, invasion and metastatic properties of cancerous cells. This study analyses the alterations in the expression patterns of these molecules in right sided colorectal cancer (CRC), both metastatic and non-metastatic. Twenty right sided CRCs were studied. A transcriptomic approach was used, employing qPCR to analyze both the expression of the enzymes involved in heparan sulfate (HS) chains biosynthesis, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate (CS) chains, we include the study of the genes involved in the biosynthesis of these glycosaminoglycans. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences, of potential interest. Changes in proteoglycan core proteins differ depending on their location; those located intracellularly or in the extracellular matrix show very similar alteration patterns, while those located on the cell surface vary greatly depending on the nature of the tumor: glypicans 1, 3, 6 and betaglycan are affected in the non-metastatic tumors, whereas in the metastatic, only glypican-1 and syndecan-1 are modified, the latter showing opposing alterations in levels of RNA and of protein, suggesting post-transcriptional regulation in these tumors. Furthermore, in non-metastatic tumors, polymerization of glycosaminoglycan chains is modified, particularly affecting the synthesis of the tetrasaccharide linker and the initiation and elongation of CS chains, HS chains being less affected. Regarding the enzymes responsible for the modificaton of the HS chains, alterations were only found in non-metastatic tumors, affecting N-sulfation and the isoforms HS6ST1, HS3ST3B and HS3ST5. In contrast, synthesis of the CS chains suggests changes in epimerization and sulfation of the C4 and C2 in both types of tumor. Right sided CRCs show

Ovine placental steroid synthesis and metabolism in late gestation.

Science.gov (United States)

Reynolds, Lawrence P; Legacki, Erin L; Corbin, C Jo; Caton, Joel S; Vonnahme, Kimberly A; Stanley, Scott; Conley, Alan J

2018-04-14

Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude 1) that diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and 2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

Selenium utilization in thioredoxin and catalytic advantage provided by selenocysteine

International Nuclear Information System (INIS)

Kim, Moon-Jung; Lee, Byung Cheon; Hwang, Kwang Yeon; Gladyshev, Vadim N.; Kim, Hwa-Young

2015-01-01

Thioredoxin (Trx) is a major thiol-disulfide reductase that plays a role in many biological processes, including DNA replication and redox signaling. Although selenocysteine (Sec)-containing Trxs have been identified in certain bacteria, their enzymatic properties have not been characterized. In this study, we expressed a selenoprotein Trx from Treponema denticola, an oral spirochete, in Escherichia coli and characterized this selenoenzyme and its natural cysteine (Cys) homologue using E. coli Trx1 as a positive control. 75 Se metabolic labeling and mutation analyses showed that the SECIS (Sec insertion sequence) of T. denticola selenoprotein Trx is functional in the E. coli Sec insertion system with specific selenium incorporation into the Sec residue. The selenoprotein Trx exhibited approximately 10-fold higher catalytic activity than the Sec-to-Cys version and natural Cys homologue and E. coli Trx1, suggesting that Sec confers higher catalytic activity on this thiol-disulfide reductase. Kinetic analysis also showed that the selenoprotein Trx had a 30-fold higher K m than Cys-containing homologues, suggesting that this selenoenzyme is adapted to work efficiently with high concentrations of substrate. Collectively, the results of this study support the hypothesis that selenium utilization in oxidoreductase systems is primarily due to the catalytic advantage provided by the rare amino acid, Sec. - Highlights: • The first characterization of a selenoprotein Trx is presented. • The selenoenzyme Trx exhibits 10-fold higher catalytic activity than Cys homologues. • Se utilization in Trx is primarily due to the catalytic advantage provided by Sec residue

Selenium utilization in thioredoxin and catalytic advantage provided by selenocysteine

Energy Technology Data Exchange (ETDEWEB)

Kim, Moon-Jung [Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705-717 (Korea, Republic of); Lee, Byung Cheon [Division of Genetics, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Division of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Hwang, Kwang Yeon [Division of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Gladyshev, Vadim N. [Division of Genetics, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Kim, Hwa-Young, E-mail: hykim@ynu.ac.kr [Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705-717 (Korea, Republic of)

2015-06-12

Thioredoxin (Trx) is a major thiol-disulfide reductase that plays a role in many biological processes, including DNA replication and redox signaling. Although selenocysteine (Sec)-containing Trxs have been identified in certain bacteria, their enzymatic properties have not been characterized. In this study, we expressed a selenoprotein Trx from Treponema denticola, an oral spirochete, in Escherichia coli and characterized this selenoenzyme and its natural cysteine (Cys) homologue using E. coli Trx1 as a positive control. {sup 75}Se metabolic labeling and mutation analyses showed that the SECIS (Sec insertion sequence) of T. denticola selenoprotein Trx is functional in the E. coli Sec insertion system with specific selenium incorporation into the Sec residue. The selenoprotein Trx exhibited approximately 10-fold higher catalytic activity than the Sec-to-Cys version and natural Cys homologue and E. coli Trx1, suggesting that Sec confers higher catalytic activity on this thiol-disulfide reductase. Kinetic analysis also showed that the selenoprotein Trx had a 30-fold higher K{sub m} than Cys-containing homologues, suggesting that this selenoenzyme is adapted to work efficiently with high concentrations of substrate. Collectively, the results of this study support the hypothesis that selenium utilization in oxidoreductase systems is primarily due to the catalytic advantage provided by the rare amino acid, Sec. - Highlights: • The first characterization of a selenoprotein Trx is presented. • The selenoenzyme Trx exhibits 10-fold higher catalytic activity than Cys homologues. • Se utilization in Trx is primarily due to the catalytic advantage provided by Sec residue.

Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

International Nuclear Information System (INIS)

Martin-Skilton, Rebeca; Lavado, Ramon; Thibaut, Remi; Minier, Christophe; Porte, Cinta

2006-01-01

Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17β-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period

Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

Energy Technology Data Exchange (ETDEWEB)

Martin-Skilton, Rebeca [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Lavado, Ramon [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Thibaut, Remi [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Minier, Christophe [Laboratoire d' Ecotoxicologie, Universite du Havre, 25 rue Philippe Lebon, B.P. 540, F-76058 Le Havre (France); Porte, Cinta [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)]. E-mail: cpvqam@cid.csic.es

2006-05-15

Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17{beta}-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period.

Phosphorus-containing cyclodextrins. Characteristics of the synthesis and chemical behaviour

International Nuclear Information System (INIS)

Grachev, M K

2013-01-01

Published data on the preparation of phosphorus-containing cyclodextrins are summarized. It is demonstrated that some significant features of their synthesis and chemical behaviour are caused by specific supramolecular interactions involving the inner chiral cavity of cyclodextrins capable of incorporating various guests, which often leads to alteration of customary routes of chemical transformations. The possibilities of practical applications of phosphorus-containing cyclodextrins are briefly analyzed. The bibliography includes 89 references

In utero exposure to chloroquine alters sexual development in the male fetal rat

International Nuclear Information System (INIS)

Clewell, Rebecca A.; Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

2009-01-01

Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

DNA alterations photosensitized by tetracycline and some of its derivatives

International Nuclear Information System (INIS)

Piette, J.; Decuyper, J.; Van de Vorst, A.

1986-01-01

Bacteriophage M13 mp10 DNA were irradiated with near-UV light in the presence of tetracycline derivatives and primed with synthetic oligonucleotide to be used for DNA synthesis using Escherichia coli DNA polymerase. Chain terminations were observed by denaturing polyacrylamide gel electrophoresis and mapped precisely. All the synthesis stops occurred before or at the level of guanine residues, showing that the photoreaction mediated by tetracycline derivatives led to a preferential alteration of guanine residues. These lesions were demonstrated to be induced in DNA through a pathway involving singlet oxygen. Tetracycline derivatives also photoinduced the breakage of the DNA sugar-phosphate backbone monitored by the conversion of supercoiled phi X174 DNA to a relaxed form. This lesion was shown to be initiated by hydroxyl radicals. The production of this free radical has been confirmed by electron paramagnetic resonance (EPR) spin trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide as spin trap. In addition to the EPR signal due to OH radicals trapping another unassigned signal has been detected

Nucleolar proteins change in altered gravity

Science.gov (United States)

Sobol, M. A.; Kordyum, E. L.; Gonzalez-Camacho, F.; Medina, F. J.

Discovery of gravisensitivity of cells no specified to gravity perception focused continuous attention on an elucidation of mechanisms involved in altered gravity effects at the different levels of cellular organization A nucleolus is the nuclear domain in which the major portion of ribosome biogenesis takes place This is a basic process for cell vitality beginning with the transcription of rDNA followed by processing newly synthesized pre-rRNA molecules A wide range of nucleolar proteins plays a highly significant role in all stages of biosynthesis of ribosomes Different steps of ribosome biogenesis should respond to various external factors affecting generally the cell metabolism Nevertheless a nucleolus remains not enough studied under the influence of altered environmental conditions For this reason we studied root apices from 2-day old Lepidium sativum seedlings germinated and grown under slow horizontal clinorotation and stationary conditions in darkness The extraction of cell nuclei followed by sequential fractionation of nuclear proteins according to their solubility in buffers of increasing ionic strength was carried out This procedure gave rise to 5 distinct fractions We analyzed nuclear subproteomes of the most soluble fraction called S2 It is actually a functionally significant fraction consisting of ribonucleoproteins actively engaged in pre-rRNA synthesis and processing 2D-electrophoresis of S2 fraction proteins was carried out The gels were silver stained and stained gels were scanned and analyzed

Diet-induced obesity alters protein synthesis: Tissue-specific effects in fasted vs. fed mice

OpenAIRE

Anderson, Stephanie R.; Gilge, Danielle A.; Steiber, Alison L.; Previs, Stephen F.

2008-01-01

The influence of obesity on protein dynamics is not clearly understood. We have designed experiments to test the hypothesis that obesity impairs the stimulation of tissue-specific protein synthesis following nutrient ingestion. C57BL/6J mice were randomized into two groups: group 1 (control, n = 16) were fed a low-fat, high-carbohydrate diet and group 2 (experimental, n = 16) were fed a high-fat, low-carbohydrate diet ad libitum for 9 weeks. On the experiment day, all mice were fasted for 6 h...

Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.

Science.gov (United States)

Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

2017-01-01

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity ( MPL, JAK2, CALR ) and loss-of-function (LOF) activity of negative regulators ( CBL, LNK ) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of MPL leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF THPO or MPL mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.

Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies.

Science.gov (United States)

Stan, Ana D; Lewis, David A

2012-06-01

Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain's own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

ALTER-GLOBALISM AND DEVELOPMENT IN MIGRATION CONDITIONS. THE CASE OF AN EAST EUROPEAN COUNTRY

OpenAIRE

Alina HALLER

2017-01-01

Globalisation is a process that brings advantages and disadvantages to all states, regardless of their stage of development. The relative deprivation, especially the financial one, of the developing countries is a reason of frustration, which motivates the emigration decision; hence our orientation to alter-globalism. In this paper, I intend to highlight by means of analysis, synthesis, deduction, induction, and statistic data, the causes and types of migration in Romania’s case, one of the m...

Polypepide synthesis in response to 20-hydroxyecdysone, with particular reference to calcium-binding proteins, in the epidermis of a larval insect

Energy Technology Data Exchange (ETDEWEB)

Ouellette, Y.

1988-01-01

Epidermal cells respond to 20-hydroxyecdysone (20HE) by altering their morphology, rate of proliferation and level of cell-to-cell communication. To study changes in polypeptide synthesis induced by 20HE, epidermal polypeptides from the midinstar larvae of the mealworm Tenebrio molitor were separated by one- and two-dimensional polyacrylamide gel electrophoresis. {sup 35}S-methionine-labelled polypeptides were extracted from cells incubated either in the absence or presence of 2{mu}g/ml 20HE for 14-16 h in vitro. Cells incubated with the hormone incorporated 28% more label into polypeptides. Over 250 polypeptides were detected in total cell lysates by this technique. Polypeptides that showed altered rates of synthesis in response to 20HE treatment were identified and characterized.

Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs

Science.gov (United States)

Ramnanan, Christopher J.; Saraswathi, Viswanathan; Smith, Marta S.; Donahue, E. Patrick; Farmer, Ben; Farmer, Tiffany D.; Neal, Doss; Williams, Philip E.; Lautz, Margaret; Mari, Andrea; Cherrington, Alan D.; Edgerton, Dale S.

2011-01-01

In rodents, acute brain insulin action reduces blood glucose levels by suppressing the expression of enzymes in the hepatic gluconeogenic pathway, thereby reducing gluconeogenesis and endogenous glucose production (EGP). Whether a similar mechanism is functional in large animals, including humans, is unknown. Here, we demonstrated that in canines, physiologic brain hyperinsulinemia brought about by infusion of insulin into the head arteries (during a pancreatic clamp to maintain basal hepatic insulin and glucagon levels) activated hypothalamic Akt, altered STAT3 signaling in the liver, and suppressed hepatic gluconeogenic gene expression without altering EGP or gluconeogenesis. Rather, brain hyperinsulinemia slowly caused a modest reduction in net hepatic glucose output (NHGO) that was attributable to increased net hepatic glucose uptake and glycogen synthesis. This was associated with decreased levels of glycogen synthase kinase 3β (GSK3β) protein and mRNA and with decreased glycogen synthase phosphorylation, changes that were blocked by hypothalamic PI3K inhibition. Therefore, we conclude that the canine brain senses physiologic elevations in plasma insulin, and that this in turn regulates genetic events in the liver. In the context of basal insulin and glucagon levels at the liver, this input augments hepatic glucose uptake and glycogen synthesis, reducing NHGO without altering EGP. PMID:21865644

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

Science.gov (United States)

Ferrando, A. A.; Lane, H. W.; Stuart, C. A.; Davis-Street, J.; Wolfe, R. R.

1996-01-01

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P protein synthesis (PS; P protein also decreased by 46% (P protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

International Nuclear Information System (INIS)

Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

1987-01-01

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14 C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis

Analyses of Selenotranscriptomes and Selenium Concentrations in Response to Dietary Selenium Deficiency and Age Reveal Common and Distinct Patterns by Tissue and Sex in Telomere-Dysfunctional Mice.

Science.gov (United States)

Cao, Lei; Zhang, Li; Zeng, Huawei; Wu, Ryan Ty; Wu, Tung-Lung; Cheng, Wen-Hsing

2017-10-01

Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity. Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice. Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes. Results: Dietary selenium deficiency decreased ( P ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; P ≤ 0.05) in the plasma of males only but decreased (12-46%; P selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; P ≤ 0.05) iodothyronine deiodinase 2 ( Dio2 ) and selenoprotein N ( Selenon ) in the kidneys of males. Age upregulated (11-44%; P selenium status and selenotranscriptomes because of dietary selenium deficiency and age. © 2017 American Society for Nutrition.

Systematic Review and Meta-Analysis on Incidence of Altered Sensation of Mandibular Implant Surgery

Science.gov (United States)

Lin, Chia-Shu; Wu, Shih-Yun; Huang, Hsin-Yi; Lai, Yu-Lin

2016-01-01

Altered sensation (including paresthesia, dysesthesia and hypoesthesia) after mandibular implant surgery may indicate transient or permanent injury of the inferior alveolar nerve and the mental branch, and considerably lower patients’ satisfaction about the therapy. Previous studies have shown a great degree of variability on the incidence of altered sensation. We here reported the incidence of altered sensation after mandibular implant surgery based on a meta-analysis of 26 articles published between 1990.1.1 and 2016.1.1. Study quality and risk of bias was assessed and the studies with a lower score were excluded in the meta-analysis. Data synthesis was performed using the logistic-normal random-effect model. The meta-analyses revealed that the short-term (10 days after implant placement) and long-term (1 year after implant placement) incidence was 13% (95% CI, 6%-25%) and 3% (95% CI, 1%-7%), respectively. (2) For the patients who initially reported altered sensation, 80% (95% CI, 52%-94%) of them would return to normal sensation within 6 months after surgery, and 91% (95% CI, 78%-96%) of them would return to normal sensation one year after surgery. We concluded that dentist-patient communication about the risk of altered sensation is critical to treatment planning, since the short-term incidence of altered sensation is substantial (13%). When a patient reports altered sensation, regular assessment for 6 months would help tracing the changes of symptoms. In terms of long-term follow-up (1 year after surgery), the incidence is much lower (3%) and most patients (91%) would return to normal sensation. PMID:27100832

Systematic Review and Meta-Analysis on Incidence of Altered Sensation of Mandibular Implant Surgery.

Directory of Open Access Journals (Sweden)

Chia-Shu Lin

Full Text Available Altered sensation (including paresthesia, dysesthesia and hypoesthesia after mandibular implant surgery may indicate transient or permanent injury of the inferior alveolar nerve and the mental branch, and considerably lower patients' satisfaction about the therapy. Previous studies have shown a great degree of variability on the incidence of altered sensation. We here reported the incidence of altered sensation after mandibular implant surgery based on a meta-analysis of 26 articles published between 1990.1.1 and 2016.1.1. Study quality and risk of bias was assessed and the studies with a lower score were excluded in the meta-analysis. Data synthesis was performed using the logistic-normal random-effect model. The meta-analyses revealed that the short-term (10 days after implant placement and long-term (1 year after implant placement incidence was 13% (95% CI, 6%-25% and 3% (95% CI, 1%-7%, respectively. (2 For the patients who initially reported altered sensation, 80% (95% CI, 52%-94% of them would return to normal sensation within 6 months after surgery, and 91% (95% CI, 78%-96% of them would return to normal sensation one year after surgery. We concluded that dentist-patient communication about the risk of altered sensation is critical to treatment planning, since the short-term incidence of altered sensation is substantial (13%. When a patient reports altered sensation, regular assessment for 6 months would help tracing the changes of symptoms. In terms of long-term follow-up (1 year after surgery, the incidence is much lower (3% and most patients (91% would return to normal sensation.

Co-ordinate transcriptional regulation of dopamine synthesis genes by alpha-synuclein in human neuroblastoma cell lines.

Science.gov (United States)

Baptista, Melisa J; O'Farrell, Casey; Daya, Sneha; Ahmad, Rili; Miller, David W; Hardy, John; Farrer, Matthew J; Cookson, Mark R

2003-05-01

Abnormal accumulation of alpha-synuclein in Lewy bodies is a neuropathological hallmark of both sporadic and familial Parkinson's disease (PD). Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic cell death occurs remains unknown. We investigated transcriptional changes in neuroblastoma cell lines transfected with either normal or mutant (A30P or A53T) alpha-synuclein using microarrays, with confirmation of selected genes by quantitative RT-PCR. Gene products whose expression was found to be significantly altered included members of diverse functional groups such as stress response, transcription regulators, apoptosis-inducing molecules, transcription factors and membrane-bound proteins. We also found evidence of altered expression of dihydropteridine reductase, which indirectly regulates the synthesis of dopamine. Because of the importance of dopamine in PD, we investigated the expression of all the known genes in dopamine synthesis. We found co-ordinated downregulation of mRNA for GTP cyclohydrolase, sepiapterin reductase (SR), tyrosine hydroxylase (TH) and aromatic acid decarboxylase by wild-type but not mutant alpha-synuclein. These were confirmed at the protein level for SR and TH. Reduced expression of the orphan nuclear receptor Nurr1 was also noted, suggesting that the co-ordinate regulation of dopamine synthesis is regulated through this transcription factor.

Effect of long-term selenium supplementation on mortality

DEFF Research Database (Denmark)

Rayman, Margaret P.; Winther, Kristian Hillert; Pastor-Barriuso, Roberto

2018-01-01

Background: Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ∼ 125 μg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained...... concentrations higher than this are beneficial, or indeed detrimental, is unknown. Objective: In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels. Design: The Denmark PRECISE study was a single...... for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 μg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were followed up for mortality for a further 10 years (through March 31, 2015...

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

Directory of Open Access Journals (Sweden)

Kieron M. G. O’Connell

2012-06-01

Full Text Available Two-directional synthesis represents an ideal strategy for the rapid elaboration of simple starting materials and their subsequent transformation into complex molecular architectures. As such, it is becoming recognised as an enabling technology for diversity-oriented synthesis. Herein, we provide a thorough account of our work combining two-directional synthesis with diversity-oriented synthesis, with particular reference to the synthesis of polycyclic alkaloid scaffolds.

Alterations of cortical GABA neurons and network oscillations in schizophrenia.

Science.gov (United States)

Gonzalez-Burgos, Guillermo; Hashimoto, Takanori; Lewis, David A

2010-08-01

The hypothesis that alterations of cortical inhibitory gamma-aminobutyric acid (GABA) neurons are a central element in the pathology of schizophrenia has emerged from a series of postmortem studies. How such abnormalities may contribute to the clinical features of schizophrenia has been substantially informed by a convergence with basic neuroscience studies revealing complex details of GABA neuron function in the healthy brain. Importantly, activity of the parvalbumin-containing class of GABA neurons has been linked to the production of cortical network oscillations. Furthermore, growing knowledge supports the concept that gamma band oscillations (30-80 Hz) are an essential mechanism for cortical information transmission and processing. Herein we review recent studies further indicating that inhibition from parvalbumin-positive GABA neurons is necessary to produce gamma oscillations in cortical circuits; provide an update on postmortem studies documenting that deficits in the expression of glutamic acid decarboxylase67, which accounts for most GABA synthesis in the cortex, are widely observed in schizophrenia; and describe studies using novel, noninvasive approaches directly assessing potential relations between alterations in GABA, oscillations, and cognitive function in schizophrenia.

Nano crystals-Related Synthesis, Assembly, and Energy Applications

International Nuclear Information System (INIS)

Dai, Q.; Hu, M.Z.; Yu, B.Z.; William, W.; Seo, J.

2011-01-01

Fundamental material properties have been dramatically altered in the nano scale regime because of quantum confinement effect. The unique size-tunable functionalities of nano materials make them involved in an extensive variety of energy applications, such as light-emitting diodes and solar cells. These applications have been demonstrated to cut energy consumption. In response to the ever-growing energy demands as well as the concerns of global warming, researchers are actively placing their enormous emphasis on the exploration of energy savings. During this exploration, the primary stage requires the design of appropriate strategies for the synthesis of high-quality nano crystals in terms of size uniformity and superior optical/electronic properties. Especially, there is a need to seek green-chemistry approaches for the synthesis of environmentally benign and user-friendly nano crystals. Another recent area of focus is the use of individual nano crystals as building blocks for self-assembly, providing new opportunities to improve the nano crystal performance

Effect of altered thyroid states on the distribution of intraperitoneally injected cadmium-109 in rats

International Nuclear Information System (INIS)

Mann, S.J.

1975-01-01

Metals bind to proteins in the blood and are transported in this bound state. The synthesis of proteins is altered in disease states. There may be an increase, a decrease, or a change in the protein fraction makeup, depending on the type and severity of the disease. Total protein synthesis is increased in hyperthyroidism; decreased in hypothyroidism. These changes alter the uptake and distribution of minerals and metals. This study was designed to determine the effect of altered thyroid states on the distribution of cadmium, a toxic environmental pollutant, in rats. The main experiment consisted of injecting rats with Cd-109 after 15 days of drug pretreatment for induction of hypothyroidism and hyperthyroidism. Cadmium levels in the samples were expressed as percentage of activity per organ (P) and percentage of activity per gram of tissue (A). The results showed that drug treatment affected organ weights. Hypothyroid livers weighed significantly less than hyperthyroid and euthyroid livers. Kidney and spleen weights of all three treatment groups were significantly different from each other. Those of hypothyroid rats weighed the least; those of hyperthyroid rats weighed the most. Expressed as P values, livers of the three treatment groups were not different, but hyperthyroid kidneys and spleens had significantly higher levels of cadmium. The A values of hypothyroid livers, kidneys, and spleens were higher than those of the other two treatment groups. Bone, muscle, testes, and blood samples showed extensive variability, and for this reason statistical analyses were not run. There were trends, but it was evident that the overall treatment effects on cadmium levels in these tissues were negligible

The Timing of Multiple Retrieval Events Can Alter GluR1 Phosphorylation and the Requirement for Protein Synthesis in Fear Memory Reconsolidation

Science.gov (United States)

Jarome, Timothy J.; Kwapis, Janine L.; Werner, Craig T.; Parsons, Ryan G.; Gafford, Georgette M.; Helmstetter, Fred J.

2012-01-01

Numerous studies have indicated that maintaining a fear memory after retrieval requires de novo protein synthesis. However, no study to date has examined how the temporal dynamics of repeated retrieval events affect this protein synthesis requirement. The present study varied the timing of a second retrieval of an established auditory fear memory…

Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.

Science.gov (United States)

Ooi, Cher-Pheng; Smith, Terry K; Gluenz, Eva; Wand, Nadina Vasileva; Vaughan, Sue; Rudenko, Gloria

2018-06-01

The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post-mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol-anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans-face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi. © 2018 The Authors. Traffic published by John Wiley & Sons Ltd.

Amylase and chymotrypsinogen synthesis and secretion by the anesthetized rat pancreas

International Nuclear Information System (INIS)

Iovanna, J.; Giorgi, D.; Dagorn, J.C.

1987-01-01

To investigate the origin of nonparallel secretion, pancreatic juice was collected in the anesthetized rat, during infusion of [ 3 H]phenylalanine. In the basal state, the amylase to chymotrypsinogen ratios of activities and of [ 3 H] incorporations were 3.5 and 2.5 times higher than in the homogenate, respectively. Both ratios decreased to the value in the homogenate upon caerulein stimulation (600 ng/kg). Inhibition of protein synthesis by cycloheximide (15 ng/kg) did not alter enzyme secretion ratios, and depressed basal protein output only partly, suggesting similar secretory pathways for basal and stimulated secretion. Finally, when [ 3 H]phenylalanine was given before anesthesia, the amylase to chymotrypsinogen ratio of incorporations was again higher in basal secretion than in homogenate, even when further protein synthesis was blocked by cycloheximide before urethane injection. Hence, basal secretion comes from a pancreatic compartment which is functional, although minor, in the conscious animal, and shows a higher rate of amylase synthesis, compared to chymotrypsinogen, than the rest of the gland. It could consist of a subpopulation of acinar cells

Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

International Nuclear Information System (INIS)

Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

1987-01-01

The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

Nucleic acid metabolism in sea urchin embryos and its alteration after x-irradiation

International Nuclear Information System (INIS)

Kimura, I.

1974-01-01

Nucleic acid metabolism observed during embryogenesis of the sea urchin (Hemicentrotus pulcherrimus) and its alteration after x irradiation were studied on both qualitative and quantitative bases. MAK chromatographic analysis has revealed that the stage-dependent synthesis of RNA occurred during embryogenesis: some RNA families were observed specifically for early cleavage stage, not being observed at stages later than gastrulation. Further, they were modified by irradiation pari passu with delay and inhibition of cleavage. These results were discussed in comparison with our previous results on normal and regenerating rat liver

Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

Science.gov (United States)

Awara, W; Hillier, K; Jones, D

1986-12-01

The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect.

Di(2-ethylhexyl)phthalate Alters the Synthesis and β-Oxidation of Fatty Acids and Hinders ATP Supply in Mouse Testes via UPLC-Q-Exactive Orbitrap MS-Based Metabonomics Study.

Science.gov (United States)

Shen, Guolin; Zhou, Lili; Liu, Wei; Cui, Yuan; Xie, Wenping; Chen, Huiming; Yu, Wenlian; Li, Wentao; Li, Haishan

2017-06-21

Di(2-ethylhexyl) phthalate (DEHP) is considered to be an environmental endocrine disruptor at high levels of general exposure. Studies show that DEHP may cause testicular toxicity on human being. In this study, metabonomics techniques were used to identify differential endogenous metabolites, draw the network metabolic pathways, and conduct network analysis, to determine the underlying mechanisms of testicular toxicity induced by DEHP. The results showed that DEHP inhibited synthesis and accelerated β-oxidation of fatty acids and impaired the tricarboxylic acid cycle (TCA cycle) and gluconeogenesis, resulting in lactic acid accumulation and an insufficient ATP supply in the microenvironment of the testis. These alterations led to testicular atrophy and, thus, may be the underlying causes of testicular toxicity. DEHP also inhibited peroxisome proliferator activated receptors in the testis, which may be another potential reason for the testicular atrophy. These findings provided new insights to better understand the mechanisms of testicular toxicity induced by DEHP exposure.

A Phex Mutation in a Murine Model of X-linked Hypophosphatemia Alters Phosphate Responsiveness of Bone Cells

OpenAIRE

Ichikawa, Shoji; Austin, Anthony M.; Gray, Amie K.; Econs, Michael J.

2012-01-01

Mutations in the PHEX gene cause X-linked hypophosphatemia (XLH). Hypophosphatemia in XLH results from increased circulating levels of a phosphaturic hormone, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D (calcitriol) synthesis. The current standard therapy for XLH – high dose phosphate and calcitriol – further increases FGF23 concentrations, suggesting that patients with XLH may have an altered response to extracellular phosphate...

Requirements of glycerol and fatty acid for triglyceride synthesis and ketogenesis by hepatocytes from normal and triiodothyronine-treated rats

International Nuclear Information System (INIS)

Olubadewo, J.O.; Heimberg, M.

1985-01-01

Hepatocytes from T3-treated rats synthesized less triglyceride and more ketone bodies from [1- 14 C]oleate at all concentrations from 0-2 mM, than did hepatocytes from euthyroid animals; addition of 1.0 mM glycerol increased triglyceride synthesis and reduced ketogenesis in hepatocytes from T3-treated rats to the rates observed in euthyroid hepatocytes in the absence of added glycerol. Glycerol did not alter triglyceride synthesis, but reduced ketogenesis genesis by euthyroid hepatocytes. It is probable from these and other data that, in the hyperthyroid rat, glycero-3-P, and not fatty acid, is rate limiting for synthesis of triglyceride, and, secondarily for reducing rates of ketogenesis in the hepatocyte

Sickle erythrocytes inhibit human endothelial cell DNA synthesis

International Nuclear Information System (INIS)

Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K.

1990-01-01

Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling

A cross-biome synthesis of soil respiration and its determinants under simulated precipitation changes.

Science.gov (United States)

Liu, Lingli; Wang, Xin; Lajeunesse, Marc J; Miao, Guofang; Piao, Shilong; Wan, Shiqiang; Wu, Yuxin; Wang, Zhenhua; Yang, Sen; Li, Ping; Deng, Meifeng

2016-04-01

Soil respiration (Rs) is the second-largest terrestrial carbon (C) flux. Although Rs has been extensively studied across a broad range of biomes, there is surprisingly little consensus on how the spatiotemporal patterns of Rs will be altered in a warming climate with changing precipitation regimes. Here, we present a global synthesis Rs data from studies that have manipulated precipitation in the field by collating studies from 113 increased precipitation treatments, 91 decreased precipitation treatments, and 14 prolonged drought treatments. Our meta-analysis indicated that when the increased precipitation treatments were normalized to 28% above the ambient level, the soil moisture, Rs, and the temperature sensitivity (Q10) values increased by an average of 17%, 16%, and 6%, respectively, and the soil temperature decreased by -1.3%. The greatest increases in Rs and Q10 were observed in arid areas, and the stimulation rates decreased with increases in climate humidity. When the decreased precipitation treatments were normalized to 28% below the ambient level, the soil moisture and Rs values decreased by an average of -14% and -17%, respectively, and the soil temperature and Q10 values were not altered. The reductions in soil moisture tended to be greater in more humid areas. Prolonged drought without alterations in the amount of precipitation reduced the soil moisture and Rs by -12% and -6%, respectively, but did not alter Q10. Overall, our synthesis suggests that soil moisture and Rs tend to be more sensitive to increased precipitation in more arid areas and more responsive to decreased precipitation in more humid areas. The responses of Rs and Q10 were predominantly driven by precipitation-induced changes in the soil moisture, whereas changes in the soil temperature had limited impacts. Finally, our synthesis of prolonged drought experiments also emphasizes the importance of the timing and frequency of precipitation events on ecosystem C cycles. Given these

“Synthesis-on” and “synthesis-off” modes of carbon arc operation during synthesis of carbon nanotubes

International Nuclear Information System (INIS)

Yatom, Shurik; Selinsky, Rachel S.

2017-01-01

Arc discharge synthesis of single-walled carbon nanotubes (SWCNTs) remains largely uncontrollable, due to incomplete understanding of the synthetic process itself. Here, we show that synthesis of SWCNTs by a carbon arc may not constitute a single continuous process, but may instead consist of two distinct modes. One of these, a “synthesis-on” mode, produces the majority of the nanomaterials. During the synthesis-on mode, proportionally more carbon nanotubes are collected than in another mode, a “synthesis-off” mode. Both synthesis-on and synthesis-off modes for a typical arc configuration, employing a hollow anode filled with a mixture of powdered metal catalyst and graphite, were characterized by using in situ electrical, imaging, and spectroscopic diagnostics, along with ex situ imaging and spectroscopy. The synthesis-on mode duration is rare compared to the total arc run-time, helping to explain the poor selectivity found in the final collected products, a known inadequacy of arc synthesis. Finally, the rarity of the synthesis on mode occurence may be due to the synthesis off mode being more favorable energetically.

Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

Science.gov (United States)

Bonde, Ylva; Breuer, Olof; Lütjohann, Dieter; Sjöberg, Stefan; Angelin, Bo; Rudling, Mats

2014-01-01

Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. PMID:25172631

Multiple alteration events in the East Bull Lake anorthosite-gabbro layered complex, NE Ontario, Canada: evidence from fracture mineralogy and 40Ar-39Ar dating

International Nuclear Information System (INIS)

Kamineni, D.C.; McCrank, G.F.; Stone, D.; Geological Survey of Canada, Ottawa, Ontario)

1987-01-01

The East Bull Lake anorthosite-gabbro layered complex contains a variety of alteration minerals. Some of the more common ones are calcic amphiboles, biotite, epidote, adularia, quartz, chlorite, calcite, prehnite, pumpellyite, laumontite, gypsum, iron hydroxides and clays. The mode of occurrence and the data related to the stability of the alteration minerals suggest that they were formed under pressure-temperature conditions of: (1) epidote-amphibolite/greenschist facies; (2) prehnite-pumpellyite facies; (3) zeolite facies; and (4) low-temperature mineral facies. 40 Ar- 39 Ar data of hornblende and adularia indicate that the pluton is affected by distinct alteration events. Two mafic dyke intrusions, that overlap the alteration events, are recognised in the pluton. Synthesis of available radiometric ages suggests that the pluton intruded at 2472 +- 70 Ma, and was subjected to alteration as late as the Paleozoic and Cenozoic Eras. (author)

Nucleolar TRF2 attenuated nucleolus stress-induced HCC cell-cycle arrest by altering rRNA synthesis.

Science.gov (United States)

Yuan, Fuwen; Xu, Chenzhong; Li, Guodong; Tong, Tanjun

2018-05-03

The nucleolus is an important organelle that is responsible for the biogenesis of ribosome RNA (rRNA) and ribosomal subunits assembly. It is also deemed to be the center of metabolic control, considering the critical role of ribosomes in protein translation. Perturbations of rRNA synthesis are closely related to cell proliferation and tumor progression. Telomeric repeat-binding factor 2 (TRF2) is a member of shelterin complex that is responsible for telomere DNA protection. Interestingly, it was recently reported to localize in the nucleolus of human cells in a cell-cycle-dependent manner, while the underlying mechanism and its role on the nucleolus remained unclear. In this study, we found that nucleolar and coiled-body phosphoprotein 1 (NOLC1), a nucleolar protein that is responsible for the nucleolus construction and rRNA synthesis, interacted with TRF2 and mediated the shuttle of TRF2 between the nucleolus and nucleus. Abating the expression of NOLC1 decreased the nucleolar-resident TRF2. Besides, the nucleolar TRF2 could bind rDNA and promoted rRNA transcription. Furthermore, in hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, TRF2 overexpression participated in the nucleolus stress-induced rRNA inhibition and cell-cycle arrest.

Altered sterol metabolism in budding yeast affects mitochondrial iron-sulfur (Fe-S) cluster synthesis.

Science.gov (United States)

Ward, Diane M; Chen, Opal S; Li, Liangtao; Kaplan, Jerry; Bhuiyan, Shah Alam; Natarajan, Selvamuthu K; Bard, Martin; Cox, James E

2018-05-17

Ergosterol synthesis is essential for cellular growth and viability of the budding yeast Saccharomyces cerevisiae, and intracellular sterol distribution and homeostasis are therefore highly regulated in this species. Erg25 is an iron-containing C4-methyl sterol oxidase that contributes to the conversion of 4,4-dimethylzymosterol to zymosterol, a precursor of ergosterol. The ERG29 gene encodes an endoplasmic reticulum (ER)-associated protein, and here we identified a role for Erg29 in the methyl sterol oxidase step of ergosterol synthesis. ERG29 deletion resulted in lethality in respiring cells, but respiration-incompetent (Rho- or Rho0) cells survived, suggesting that Erg29 loss leads to accumulation of oxidized sterol metabolites that affect cell viability. Down-regulation of ERG29 expression in Δerg29 cells indeed led to accumulation of methyl sterol metabolites, resulting in increased mitochondrial oxidants and a decreased ability of mitochondria to synthesize iron-sulfur (Fe-S) clusters due to reduced levels of Yfh1, the mammalian frataxin homolog, which is involved in mitochondrial Fe metabolism. Using a high-copy genomic library, we identified suppressor genes that permitted growth of Δerg29 cells on respiratory substrates, and these included genes encoding the mitochondrial proteins Yfh1, Mmt1, Mmt2, and Pet20, which reversed all phenotypes associated with loss of ERG29. Of note, loss of Erg25 also resulted in accumulation of methyl sterol metabolites and also increased mitochondrial oxidants and degradation of Yfh1. We propose that accumulation of toxic intermediates of the methyl sterol oxidase reaction increase mitochondrial oxidants, which affect Yfh1 protein stability. These results indicate an interaction between sterols generated by ER proteins and mitochondrial iron metabolism. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine

International Nuclear Information System (INIS)

Cantor, J.O.; Osman, M.; Keller, S.; Cerreta, J.M.; Mandl, I.; Turino, G.M.

1984-01-01

Cross-linked elastin synthesis was measured in the intratracheal bleomycin model of interstitial pulmonary fibrosis by incorporation of 14C-lysine into the elastin-specific crosslinks, desmosine and isodesmosine. Detection of the labeled crosslinks was facilitated by development of a highly sensitive assay utilizing thin-layer electrophoresis. The results indicate that crosslinked elastin synthesis is significantly elevated from controls (p less than 0.05) at 1 to 3 weeks after exposure to bleomycin and returns to normal by 5 weeks. The increases in labeled elastin synthesis are not directly related to changes in either total lung protein synthesis or the pool size of the 14C-lysine. In comparison with collagen and glycosaminoglycan synthesis in this model of lung injury, maximal increases in cross-linked elastin formation occur later, but overlap with the elevated synthesis of these other connective tissue components. The marked increase from normal in cross-linked elastin synthesis in this model suggests that this tissue component is an important part of the fibrotic response of the pulmonary parenchyma and may play a role in the observed alterations in lung structure and function

Age and haplotype variations within FADS1 interact and associate with alterations in fatty acid composition in human male cortical brain tissue.

Directory of Open Access Journals (Sweden)

Erika Freemantle

Full Text Available Fatty acids (FA play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1/2/3 gene cluster as an important contributor to FA alterations in serum lipids as well as measures of FA desaturase index estimated by ratios of relevant FAs. The contribution to alterations of FAs within the brain by local synthesis is still a matter of debate. Thus, the impact of genetic variants in FADS genes on gene expression and brain FA levels is an important avenue to investigate.Analyses were performed on brain tissue from prefrontal cortex Brodmann area 47 (BA47 of 61 male subjects of French Canadian ancestry ranging in age from young adulthood to middle age (18-58 years old, with the exception of one teenager (15 years old. Haplotype tagging SNPs were selected using the publicly available HapMap genotyping dataset in conjunction with Haploview. DNA sequencing was performed by the Sanger method and gene expression was measured by quantitative real-time PCR. FAs in brain tissue were analysed by gas chromatography. Variants in the FADS1 gene region were sequenced and analyzed for their influence on both FADS gene expression and FAs in brain tissue.Our results suggest an association of the minor haplotype with alteration in estimated fatty acid desaturase activity. Analysis of the impact of DNA variants on expression and alternative transcripts of FADS1 and FADS2, however, showed no differences. Furthermore, there was a significant interaction between haplotype and age on certain brain FA levels.This study suggests that genetic variability in the FADS genes cluster, previously shown to be implicated in alterations in peripheral FA levels, may also affect FA composition in brain tissue, but not likely by local synthesis.

Altered Expression of Genes Implicated in Xylan Biosynthesis Affects Penetration Resistance against Powdery Mildew.

Science.gov (United States)

Chowdhury, Jamil; Lück, Stefanie; Rajaraman, Jeyaraman; Douchkov, Dimitar; Shirley, Neil J; Schwerdt, Julian G; Schweizer, Patrick; Fincher, Geoffrey B; Burton, Rachel A; Little, Alan

2017-01-01

Heteroxylan has recently been identified as an important component of papillae, which are formed during powdery mildew infection of barley leaves. Deposition of heteroxylan near the sites of attempted fungal penetration in the epidermal cell wall is believed to enhance the physical resistance to the fungal penetration peg and hence to improve pre-invasion resistance. Several glycosyltransferase (GT) families are implicated in the assembly of heteroxylan in the plant cell wall, and are likely to work together in a multi-enzyme complex. Members of key GT families reported to be involved in heteroxylan biosynthesis are up-regulated in the epidermal layer of barley leaves during powdery mildew infection. Modulation of their expression leads to altered susceptibility levels, suggesting that these genes are important for penetration resistance. The highest level of resistance was achieved when a GT43 gene was co-expressed with a GT47 candidate gene, both of which have been predicted to be involved in xylan backbone biosynthesis. Altering the expression level of several candidate heteroxylan synthesis genes can significantly alter disease susceptibility. This is predicted to occur through changes in the amount and structure of heteroxylan in barley papillae.

Different modes of diaminopimelate synthesis and their role in cell wall integrity: a study with Corynebacterium glutamicum.

Science.gov (United States)

Wehrmann, A; Phillipp, B; Sahm, H; Eggeling, L

1998-06-01

In eubacteria, there are three slightly different pathways for the synthesis of m-diaminopimelate (m-DAP), which is one of the key linking units of peptidoglycan. Surprisingly, for unknown reasons, some bacteria use two of these pathways together. An example is Corynebacterium glutamicum, which uses both the succinylase and dehydrogenase pathways for m-DAP synthesis. In this study, we clone dapD and prove by enzyme experiments that this gene encodes the succinylase (M(r) = 24082), initiating the succinylase pathway of m-DAP synthesis. By using gene-directed mutation, dapD, as well as dapE encoding the desuccinylase, was inactivated, thereby forcing C. glutamicum to use only the dehydrogenase pathway of m-DAP synthesis. The mutants are unable to grow on organic nitrogen sources. When supplied with low ammonium concentrations but excess carbon, their morphology is radically altered and they are less resistant to mechanical stress than the wild type. Since the succinylase has a high affinity toward its substrate and uses glutamate as the nitrogen donor, while the dehydrogenase has a low affinity and incorporates ammonium directly, the m-DAP synthesis is another example of twin activities present in bacteria for access to important metabolites such as the well-known twin activities for the synthesis of glutamate or for the uptake of potassium.

The limits of adaptation of functional protein synthesis to sever undernutrition

International Nuclear Information System (INIS)

Jahoor, F.; Bhattiprolu, S.; Reeds, P.; Forrester, T.; Boyne, M.

1994-01-01

Our goal is to determine how the stress of infections alters the adaptation to reduced food intake in children. We think that an important element is the need for hepatic synthesis of rapidly turning over acute-phase proteins, a critical factor in overall maintenance of host defenses. When the child's prior intake has been adequate, even though growth may temporarily cease, the presence of adequate amino acid stores in tissues allows the hepatic response to stress to be maintained at the same time as an adequate rate of synthesis of nutrient transport proteins. However, when the immune system is activated in a children whose nutrition is already suboptimal the ability of the liver to synthesize nutrient transport proteins is compromised thereby further impeding nutrient utilization. We will use stable isotope tracer methodology to determine the effects of severe protein energy malnutrition, with and without infection, on the rates of synthesis of nutrient transport proteins and acute-phase proteins in undernourished children at three time points during treatment; in the early resuscitative period, after appetite has returned, and at the end of the catch-up growth phase when normal growth has resumed. (author). 12 refs, 1 fig., 1 tab

The limits of adaptation of functional protein synthesis to sever undernutrition

Energy Technology Data Exchange (ETDEWEB)

Jahoor, F; Bhattiprolu, S; Reeds, P [Baylor Coll. of Medicine, Houston, TX (United States). Children` s Nutrition Research Centre; Forrester, T; Boyne, M [West Indies Univ., Mona (Jamaica). Tropical Metabolism Research Unit

1994-12-31

Our goal is to determine how the stress of infections alters the adaptation to reduced food intake in children. We think that an important element is the need for hepatic synthesis of rapidly turning over acute-phase proteins, a critical factor in overall maintenance of host defenses. When the child`s prior intake has been adequate, even though growth may temporarily cease, the presence of adequate amino acid stores in tissues allows the hepatic response to stress to be maintained at the same time as an adequate rate of synthesis of nutrient transport proteins. However, when the immune system is activated in a children whose nutrition is already suboptimal the ability of the liver to synthesize nutrient transport proteins is compromised thereby further impeding nutrient utilization. We will use stable isotope tracer methodology to determine the effects of severe protein energy malnutrition, with and without infection, on the rates of synthesis of nutrient transport proteins and acute-phase proteins in undernourished children at three time points during treatment; in the early resuscitative period, after appetite has returned, and at the end of the catch-up growth phase when normal growth has resumed. (author). 12 refs, 1 fig., 1 tab.

Insight into the influence of liquid paraffin for methanol synthesis on Cu(110) surface using continuum and atomistic models

Energy Technology Data Exchange (ETDEWEB)

Jiao, Wei-Hong [Key Laboratory of Coal Science and Technology of Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); Liu, Shi-Zhong [Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States); Zuo, Zhi-Jun, E-mail: zuozhijun@tyut.edu.cn [Key Laboratory of Coal Science and Technology of Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); Ren, Rui-Peng; Gao, Zhi-Hua [Key Laboratory of Coal Science and Technology of Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China); Huang, Wei, E-mail: huangwei@tyut.edu.cn [Key Laboratory of Coal Science and Technology of Ministry of Education and Shanxi Province, Taiyuan University of Technology, Taiyuan 030024, Shanxi (China)

2016-11-30

Highlights: • The influence of liquid paraffin is studied using continuum and atomistic models. • Liquid paraffin does not alter the reaction pathways of CO hydrogenation and WGS. • Liquid paraffin alters the reaction pathways of CO{sub 2} hydrogenation. - Abstract: Methanol synthesis from CO/CO{sub 2} hydrogenation and water-gas shift (WGS) reaction on Cu(110) in liquid paraffin and vacuum have been systematically researched with density functional theory calculation (DFT). For methanol synthesis from CO hydrogenation, the reaction pathways in liquid paraffin and vacuum are CO + H → HCO → H{sub 2}CO → H{sub 3}CO → H{sub 3}COH; in the case of WGS, the reaction pathways in liquid paraffin and vacuum are CO + 2H{sub 2}O → CO + 2OH + 2H → CO + H{sub 2}O + O + H{sub 2} → CO{sub 2} + H{sub 2}O + H{sub 2}; the reaction pathways of methanol synthesis from CO{sub 2} hydrogenation in liquid paraffin and vacuum are CO{sub 2} + H → HCOO → H{sub 2}COO → H{sub 2}CO → H{sub 3}CO → H{sub 3}COH and CO{sub 2} + H → HCOO → HCOOH → H{sub 2}COOH → H{sub 3}CO → H{sub 3}COH, respectively. The result shows that liquid paraffin does not affect the reaction mechanisms of methanol synthesis from CO and WGS, but it changes the reaction mechanisms of methanol synthesis from CO{sub 2} hydrogenation. Hirshfeld charge and the d-band centers indicate that the catalytic activity of Cu(110) in liquid paraffin is smaller than that in vacuum. Our results also show that it is necessary to consider both continuum and atomistic models in the slurry bed.

The effect of heat and radiation on the initiation and elongation processes of DNA synthesis

International Nuclear Information System (INIS)

Davies, R.C.; Bowden, G.T.; Cress, A.E.

1983-01-01

The pH step alkaline elution and alkaline sucrose gradient techniques were utilized to evaluate alterations in DNA replication (initiation and elongation) induced by heat and low dose X-irradiation in synchronized Chinese hamster ovary cells. The initiation and elongation processes of DNA synthesis were radioresistant at the G 1 /S boundary (4 hours after mitosis) while in mid S phase (9 hours after mitosis) DNA initiation and elongation were sensitive to X-irradiation. The initiation and elongation processes of DNA synthesis which were radiation resistant at the G 1 /S boundary could be inhibited by a hyperthermia treatment (43 0 C for 1 hour beginning at 4 hours after mitosis). The impairment of initiation in the heated cells was maintained through late S phase while that of elongation was reversible as judged by full recovery at 15 hours after mitosis. These data suggest that the known synergistic lethality of heat and radiation may be mediated by an impairment of initiation of DNA synthesis. (author)

Endoplasmic reticulum stress induces different molecular structural alterations in human dilated and ischemic cardiomyopathy.

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Ana Ortega

Full Text Available BACKGROUND: The endoplasmic reticulum (ER is a multifunctional organelle responsible for the synthesis and folding of proteins as well as for signalling and calcium storage, that has been linked to the contraction-relaxation process. Perturbations of its homeostasis activate a stress response in diseases such as heart failure (HF. To elucidate the alterations in ER molecular components, we analyze the levels of ER stress and structure proteins in human dilated (DCM and ischemic (ICM cardiomyopathies, and its relationship with patient's functional status. METHODS AND RESULTS: We examined 52 explanted human hearts from DCM (n = 21 and ICM (n = 21 subjects and 10 non-failing hearts as controls. Our results showed specific changes in stress (IRE1, p<0.05; p-IRE1, p<0.05 and structural (Reticulon 1, p<0.01 protein levels. The stress proteins GRP78, XBP1 and ATF6 as well as the structural proteins RRBP1, kinectin, and Nogo A and B, were upregulated in both DCM and ICM patients. Immunofluorescence results were concordant with quantified Western blot levels. Moreover, we show a novel relationship between stress and structural proteins. RRBP1, involved in procollagen synthesis and remodeling, was related with left ventricular function. CONCLUSIONS: In the present study, we report the existence of alterations in ER stress response and shaping proteins. We show a plausible effect of the ER stress on ER structure in a suitable sample of DCM and ICM subjects. Patients with higher values of RRBP1 had worse left ventricular function.

Synthesis document on the long life behavior of packages: reference operational document ''CSD-C'' 2004

International Nuclear Information System (INIS)

Helie, M.

2004-12-01

This document is realized in the framework of the law of 1991 on the radioactive wastes management. The 2004 synthesis document on long time behavior of standard packages of compacted wastes is constituted by two documents, the reference document and the operational document. This paper presents the operational model describing the packages alteration by the water and the associated radionuclide release. (A.L.B.)

Sleep Deprivation Alters Choice Strategy Without Altering Uncertainty or Loss Aversion Preferences

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O'Dhaniel A Mullette-Gillman

2015-10-01

Full Text Available Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences.

Science.gov (United States)

Mullette-Gillman, O'Dhaniel A; Kurnianingsih, Yoanna A; Liu, Jean C J

2015-01-01

Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

Regulation of porphyrin synthesis and photodynamic therapy in heavy metal intoxication.

Science.gov (United States)

Grinblat, Borislava; Pour, Nir; Malik, Zvi

2006-01-01

Protoporphyrin IX (PpIX) synthesis by malignant cells is successfully exploited for photodynamic therapy (PDT) following administration of 5-aminolevulinic acid (ALA) and light irradiation. The influence of two environmental heavy metal poisons, lead and gallium, on PpIX-synthesis and ALA-PDT was studied in two neu-ronal cell lines, SH-SY5Y neuroblastoma and PC12 pheochromocytoma. The heavy metal intoxication affected two of the heme-synthesis enzymes, ALA-dehydratase (ALAD) and porphobilinogen deaminase (PBGD). The present results show that lead poisoning significantly decreased the PBGD cellular level and inhibited its enzymatic activity, whereas the effects of gallium were less prominent. Although, the protein levels were reduced, the mRNA levels of PBGD remained unchanged during metal intoxication. These findings show additional inhibitory activity of lead on top of its classical effect on ALAD. Proteasome activity was enhanced during lead treatment, as measured by the AMC fluorigenic proteasome assay. The reduction in PBGD levels was not a consequence of PBGD mRNA reduced synthesis, which remained unchanged as shown by RT-PCR analysis. As a result of the lead poisoning, marked alterations in the cell cycle were observed, including a decreased G1 phase and an increased number of S phase cells. The efficacy of ALA-PDT was reduced in correlation with decreased activities of the enzymes during lead intoxication. We may conclude that lead poisoning adversely affects the outcome of ALA photodynamic therapy of cancer.

The effect of altered 5-hydroxytryptamine levels on beta-endorphin

Science.gov (United States)

Soliman, Karam F. A.; Mash, Deborah C.; Walker, Charles A.

1986-01-01

The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

The ecological limits of hydrologic alteration (ELOHA): A new framework for developing regional environmental flow standards

Science.gov (United States)

Poff, N.L.; Richter, B.D.; Arthington, A.H.; Bunn, S.E.; Naiman, R.J.; Kendy, E.; Acreman, M.; Apse, C.; Bledsoe, B.P.; Freeman, Mary C.; Henriksen, J.; Jacobson, R.B.; Kennen, J.G.; Merritt, D.M.; O'Keeffe, J. H.; Olden, J.D.; Rogers, K.; Tharme, R.E.; Warner, A.

2010-01-01

The flow regime is a primary determinant of the structure and function of aquatic and riparian ecosystems for streams and rivers. Hydrologic alteration has impaired riverine ecosystems on a global scale, and the pace and intensity of human development greatly exceeds the ability of scientists to assess the effects on a river-by-river basis. Current scientific understanding of hydrologic controls on riverine ecosystems and experience gained from individual river studies support development of environmental flow standards at the regional scale. 2. This paper presents a consensus view from a group of international scientists on a new framework for assessing environmental flow needs for many streams and rivers simultaneously to foster development and implementation of environmental flow standards at the regional scale. This framework, the ecological limits of hydrologic alteration (ELOHA), is a synthesis of a number of existing hydrologic techniques and environmental flow methods that are currently being used to various degrees and that can support comprehensive regional flow management. The flexible approach allows scientists, water-resource managers and stakeholders to analyse and synthesise available scientific information into ecologically based and socially acceptable goals and standards for management of environmental flows. 3. The ELOHA framework includes the synthesis of existing hydrologic and ecological databases from many rivers within a user-defined region to develop scientifically defensible and empirically testable relationships between flow alteration and ecological responses. These relationships serve as the basis for the societally driven process of developing regional flow standards. This is to be achieved by first using hydrologic modelling to build a 'hydrologic foundation' of baseline and current hydrographs for stream and river segments throughout the region. Second, using a set of ecologically relevant flow variables, river segments within the

Microbiome, inflammation, epigenetic alterations, and mental diseases.

Science.gov (United States)

Alam, Reza; Abdolmaleky, Hamid M; Zhou, Jin-Rong

2017-09-01

Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders. © 2017 Wiley Periodicals, Inc.

Synthesis document on the long time behavior of packages: operational document ''bituminous'' 2204

International Nuclear Information System (INIS)

Tiffreau, C.

2004-09-01

This document is realized in the framework of the law of 1991 on the radioactive wastes management. The 2004 synthesis document on long time behavior of bituminous sludges packages is constituted by two documents, the reference document and the operational document. This paper presents the operational model describing the water alteration of the packages and the associated radioelements release, as the gas term source and the swelling associated to the self-irradiation and the bituminous radiolysis. (A.L.B.)

Aqueous alteration of Japanese simulated waste glass P0798: Effects of alteration-phase formation on alteration rate and cesium retention

International Nuclear Information System (INIS)

Inagaki, Y.; Shinkai, A.; Idemistu, K.; Arima, T.; Yoshikawa, H.; Yui, M.

2006-01-01

Aqueous alteration tests were performed with a Japanese simulated waste glass P0798 in alkaline solutions as a function of pH or species/concentration of alkaline metals in the solution in order to evaluate the alteration conditions determining whether smectite (2:1 clay mineral) or analcime (zeolite) forms as the major alteration-phase. XRD analysis of the alteration-phases showed that smectite forms at any pH between 9.5 and 12, and analcime forms at pH above 11, though the formation also depends on species and concentrations of alkaline metals in the solution. These results cannot agree with the thermodynamically predicted phase stability, e.g., smectite is more stable than the thermodynamic prediction shows. On the basis of the results of alteration conditions, the alteration tests were performed under smectite forming conditions, where only smectite forms or no crystalline phases form, in order to evaluate the alteration rate and the mechanism of cesium release/retention. The results showed that the glass alteration proceeds slowly in proportion to square root of time under smectite forming conditions, which indicates that the alteration rate can be controlled by a diffusion process. It was suggested that the alteration rate under smectite forming conditions is independent of the pH, alkaline metal species/concentration in the solution and whether smectite actually forms or not. The results also indicated that most of cesium dissolved from the glass can be retained in the alteration-phases by reversible sorption onto smectite or irreversible incorporation into analcime, pollucite or solid solutions of them

Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis.

Science.gov (United States)

Sugita, Atsushi; Kawai, Shinji; Hayashibara, Tetsuyuki; Amano, Atsuo; Ooshima, Takashi; Michigami, Toshimi; Yoshikawa, Hideki; Yoneda, Toshiyuki

2011-01-28

Disturbed endochondral ossification in X-linked hypophosphatemia indicates an involvement of P(i) in chondrogenesis. We studied the role of the sodium-dependent P(i) cotransporters (NPT), which are a widely recognized regulator of cellular P(i) homeostasis, and the downstream events in chondrogenesis using Hyp mice, the murine homolog of human X-linked hypophosphatemia. Hyp mice showed reduced apoptosis and mineralization in hypertrophic cartilage. Hyp chondrocytes in culture displayed decreased apoptosis and mineralization compared with WT chondrocytes, whereas glycosaminoglycan synthesis, an early event in chondrogenesis, was not altered. Expression of the type III NPT Pit-1 and P(i) uptake were diminished, and intracellular ATP levels were also reduced in parallel with decreased caspase-9 and caspase-3 activity in Hyp chondrocytes. The competitive NPT inhibitor phosphonoformic acid and ATP synthesis inhibitor 3-bromopyruvate disturbed endochondral ossification with reduced apoptosis in vivo and suppressed apoptosis and mineralization in conjunction with reduced P(i) uptake and ATP synthesis in WT chondrocytes. Overexpression of Pit-1 in Hyp chondrocytes reversed P(i) uptake and ATP synthesis and restored apoptosis and mineralization. Our results suggest that cellular ATP synthesis consequent to P(i) uptake via Pit-1 plays an important role in chondrocyte apoptosis and mineralization, and that chondrogenesis is ATP-dependent.

Tailored fatty acid synthesis via dynamic control of fatty acid elongation

Energy Technology Data Exchange (ETDEWEB)

Torella, JP; Ford, TJ; Kim, SN; Chen, AM; Way, JC; Silver, PA

2013-07-09

Medium-chain fatty acids (MCFAs, 4-12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even-and odd-chain-length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, thereby slowing acyl-ACP elongation and redirecting flux from phospholipid synthesis to MCFA production. Our results show that induced protein degradation can be used to dynamically alter metabolic flux, and thereby increase the yield of a desired compound. The strategy reported herein should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product, as well as in the production of polyketides, bioplastics, and other recursively synthesized hydrocarbons for which chain-length control is desired.

Tailored fatty acid synthesis via dynamic control of fatty acid elongation

Science.gov (United States)

Torella, Joseph P.; Ford, Tyler J.; Kim, Scott N.; Chen, Amanda M.; Way, Jeffrey C.; Silver, Pamela A.

2013-01-01

Medium-chain fatty acids (MCFAs, 4–12 carbons) are valuable as precursors to industrial chemicals and biofuels, but are not canonical products of microbial fatty acid synthesis. We engineered microbial production of the full range of even- and odd-chain–length MCFAs and found that MCFA production is limited by rapid, irreversible elongation of their acyl-ACP precursors. To address this limitation, we programmed an essential ketoacyl synthase to degrade in response to a chemical inducer, thereby slowing acyl-ACP elongation and redirecting flux from phospholipid synthesis to MCFA production. Our results show that induced protein degradation can be used to dynamically alter metabolic flux, and thereby increase the yield of a desired compound. The strategy reported herein should be widely useful in a range of metabolic engineering applications in which essential enzymes divert flux away from a desired product, as well as in the production of polyketides, bioplastics, and other recursively synthesized hydrocarbons for which chain-length control is desired. PMID:23798438

Effects of secondary alteration on the composition of free and IOM-derived monocarboxylic acids in carbonaceous chondrites

Science.gov (United States)

Aponte, José C.; Alexandre, Marcelo R.; Wang, Yi; Brearley, Adrian J.; Alexander, Conel M. O.'D.; Huang, Yongsong

2011-05-01

Monocarboxylic acids (MCAs) are important astrobiologically because they are often the most abundant soluble compounds in carbonaceous chondrites (CCs) and are potential synthetic end products for many biologically important compounds. However, there has been no systematic study on the effect of parent body alteration on molecular and isotopic variability of MCAs. Since MCAs in meteorites are dominated by low molecular weight (C1-C8), highly volatile compounds, their distributions are likely to be particularly sensitive to secondary alteration processes. In contrast, the aliphatic side chains of insoluble organic matter (IOM) in CCs, whose composition has been shown to be closely related to the MCAs, may be far more resistant to secondary alteration. In the present study, we determined the distributions and isotopic ratios of free and IOM-derived MCAs in six carbonaceous chondrites with a range of classifications: Murchison (CM2), EET 87770 (CR2), ALH 83034 (CM1), ALH 83033 (CM2), MET 00430 (CV3) and WIS 91600 (C2). We compare mineralogical and petrological characteristics to the MCAs distributions to better define the processes leading to the synthesis and alteration of meteoritic MCAs. Our results show that aqueous and especially thermal alteration in the parent bodies led to major loss of free MCAs and depletion of straight relative to branched chain compounds. However, the MCAs derived from aliphatic side chains of IOM are well preserved despite of secondary alterations. The molecular and isotopic similarities of IOM-derived MCAs in different chondrite samples indicate very similar synthetic histories for organic matter in different meteorites.

mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes.

Science.gov (United States)

Fort, Patrice E; Losiewicz, Mandy K; Pennathur, Subramaniam; Jefferson, Leonard S; Kimball, Scot R; Abcouwer, Steven F; Gardner, Thomas W

2014-09-01

Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2(Akita) diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice[OPEN

Science.gov (United States)

Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

2015-01-01

Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. PMID:26002868

Synthesis of Hydroxylated Sterols in Transgenic Arabidopsis Plants Alters Growth and Steroid Metabolism1[C][W][OA

Science.gov (United States)

Beste, Lisa; Nahar, Nurun; Dalman, Kerstin; Fujioka, Shozo; Jonsson, Lisbeth; Dutta, Paresh C.; Sitbon, Folke

2011-01-01

To explore mechanisms in plant sterol homeostasis, we have here increased the turnover of sterols in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum) plants by overexpressing four mouse cDNA encoding cholesterol hydroxylases (CHs), hydroxylating cholesterol at the C-7, C-24, C-25, or C-27 positions. Compared to the wild type, the four types of Arabidopsis transformant showed varying degrees of phenotypic alteration, the strongest one being in CH25 lines, which were dark-green dwarfs resembling brassinosteroid-related mutants. Gas chromatography-mass spectrometry analysis of extracts from wild-type Arabidopsis plants revealed trace levels of α and β forms of 7-hydroxycholesterol, 7-hydroxycampesterol, and 7-hydroxysitosterol. The expected hydroxycholesterol metabolites in CH7-, CH24-, and CH25 transformants were identified and quantified using gas chromatography-mass spectrometry. Additional hydroxysterol forms were also observed, particularly in CH25 plants. In CH24 and CH25 lines, but not in CH7 ones, the presence of hydroxysterols was correlated with a considerable alteration of the sterol profile and an increased sterol methyltransferase activity in microsomes. Moreover, CH25 lines contained clearly reduced levels of brassinosteroids, and displayed an enhanced drought tolerance. Equivalent transformations of potato plants with the CH25 construct increased hydroxysterol levels, but without the concomitant alteration of growth and sterol profiles observed in Arabidopsis. The results suggest that an increased hydroxylation of cholesterol and/or other sterols in Arabidopsis triggers compensatory processes, acting to maintain sterols at adequate levels. PMID:21746809

Boron-based nanostructures: Synthesis, functionalization, and characterization

Science.gov (United States)

Bedasso, Eyrusalam Kifyalew

Boron-based nanostructures have not been explored in detail; however, these structures have the potential to revolutionize many fields including electronics and biomedicine. The research discussed in this dissertation focuses on synthesis, functionalization, and characterization of boron-based zero-dimensional nanostructures (core/shell and nanoparticles) and one-dimensional nanostructures (nanorods). The first project investigates the synthesis and functionalization of boron-based core/shell nanoparticles. Two boron-containing core/shell nanoparticles, namely boron/iron oxide and boron/silica, were synthesized. Initially, boron nanoparticles with a diameter between 10-100 nm were prepared by decomposition of nido-decaborane (B10H14) followed by formation of a core/shell structure. The core/shell structures were prepared using the appropriate precursor, iron source and silica source, for the shell in the presence of boron nanoparticles. The formation of core/shell nanostructures was confirmed using high resolution TEM. Then, the core/shell nanoparticles underwent a surface modification. Boron/iron oxide core/shell nanoparticles were functionalized with oleic acid, citric acid, amine-terminated polyethylene glycol, folic acid, and dopamine, and boron/silica core/shell nanoparticles were modified with 3-(amino propyl) triethoxy silane, 3-(2-aminoethyleamino)propyltrimethoxysilane), citric acid, folic acid, amine-terminated polyethylene glycol, and O-(2-Carboxyethyl)polyethylene glycol. A UV-Vis and ATR-FTIR analysis established the success of surface modification. The cytotoxicity of water-soluble core/shell nanoparticles was studied in triple negative breast cancer cell line MDA-MB-231 and the result showed the compounds are not toxic. The second project highlights optimization of reaction conditions for the synthesis of boron nanorods. This synthesis, done via reduction of boron oxide with molten lithium, was studied to produce boron nanorods without any

Current Knowledge on the Importance of Selenium in Food for Living Organisms: A Review.

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Kieliszek, Marek; Błażejak, Stanisław

2016-05-10

Selenium is one of the elements classified within the group of micronutrients which are necessary in trace amounts for the proper functioning of organisms. Selenium participates in the protection of cells against excess H₂O₂, in heavy metal detoxification, and regulation of the immune and reproductive systems as well. It also ensures the proper functioning of the thyroid gland. Selenium induces the occurrence of the selenoprotein synthesis process involved in the antioxidant defense mechanism of the organism. Recent years have brought much success in the studies on selenium. Anticarcinogenic properties of selenium against some cancers have been reported. Supplementation is increasingly becoming a solution to this problem. A large number of different supplementation methods are promoting studies in this area. Slight differences in the selenium content can result in excess or deficiency, therefore supplementation has to be done carefully and cautiously.

The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities.

Science.gov (United States)

Huang, Zhi; Rose, Aaron H; Hoffmann, Peter R

2012-04-01

Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in some cases. In this comprehensive article, the roles of Se and individual selenoproteins in regulating immune cell signaling and function are discussed. Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells. Data obtained from cell culture and animal models are reviewed and compared with those involving human physiology and pathophysiology, including the effects of Se levels on inflammatory or immune-related diseases including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders. Finally, the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders are discussed.

Glucocorticoids regulate surfactant protein synthesis in a pulmonary adenocarcinoma cell line

International Nuclear Information System (INIS)

O'Reilly, M.A.; Gazdar, A.F.; Clark, J.C.; Pilot-Matias, T.J.; Wert, S.E.; Hull, W.M.; Whitsett, J.A.

1989-01-01

Synthesis of pulmonary surfactant proteins SP-A, SP-B, and SP-C was demonstrated in a cell line derived from a human adenocarcinoma of the lung. The cells contained numerous lamellar inclusion bodies and formed organized groups of cells containing well-developed junctional complexes and apical microvillous membranes. Synthesis of SP-A was detected in the cells by enzyme-linked immunoabsorbent assay and by immunoprecipitation of [35S]methionine-labeled protein. SP-A was identified as an Mr 31,000-36,000 polypeptide containing asparagine-linked carbohydrate. Northern blot analysis detected SP-A mRNA of 2.2 kb. Dexamethasone (1-10 nM) enhanced the relative abundance of SP-A mRNA. Despite stimulation of SP-A mRNA, intracellular SP-A content was unaltered or inhibited by dexamethasone. SP-B and SP-C mRNAs and synthesis of the SP-B and SP-C precursors were markedly induced by dexamethasone. ProSP-B was synthesized and secreted primarily as an Mr 42,000-46,000 polypeptide. Proteolysis of the proSP-B resulted in the generation of endoglycosidase F-sensitive Mr = 19,000-21,000 and 25,000-27,000 peptides, which were detected both intra- and extracellularly. SP-C proprotein of Mr = 22,000 and smaller SP-C fragments were detected intracellularly but were not detected in the media. Mature forms of SP-B (Mr = 8,000) and SP-C (Mr = 4,000) were not detected. Glucocorticoids directly enhance the relative synthesis and mRNA of the surfactant proteins SP-A, SP-B, and SP-C. Discrepancies among SP-A mRNA, its de novo synthesis, and cell content suggest that glucocorticoid may alter both pre- and posttranslational factors modulating SP-A expression

A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice.

Science.gov (United States)

Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

2015-06-01

Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. © 2015 American Society of Plant Biologists. All rights reserved.

Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

Science.gov (United States)

Ramsay, D A; Drachman, D B; Pestronk, A

1988-10-11

The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

Directory of Open Access Journals (Sweden)

Eroukova Veronika

2008-12-01

Full Text Available Abstract Background Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, ~4700 strains for increased sensitivity to paromomycin, which targets the process of protein synthesis. Results As expected, our analysis indicated that the majority of deletion strains (134 with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45, cellular component biogenesis and organization (28, DNA maintenance (21, transport (20, others (38 and unknown (39. These may represent minor cellular target sites (side-effects for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. Conclusion We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s.

Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis.

Science.gov (United States)

Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

2008-12-03

Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, approximately 4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s).

Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs

Science.gov (United States)

Lindemann, Stephan W.; Yost, Christian C.; Denis, Melvin M.; McIntyre, Thomas M.; Weyrich, Andrew S.; Zimmerman, Guy A.

2004-05-01

The mechanisms by which neutrophils, key effector cells of the innate immune system, express new gene products in inflammation are largely uncharacterized. We found that they rapidly translate constitutive mRNAs when activated, a previously unrecognized response. One of the proteins synthesized without a requirement for transcription is the soluble IL-6 receptor , which translocates to endothelial cells and induces a temporal switch to mononuclear leukocyte recruitment. Its synthesis is regulated by a specialized translational control pathway that is inhibited by rapamycin, a bacterial macrolide with therapeutic efficacy in transplantation, inflammatory syndromes, and neoplasia. Signal-dependent translation in activated neutrophils may be a critical mechanism for alteration of the inflammatory milieu and a therapeutic target.

Suppressing Sorbitol Synthesis Substantially Alters the Global Expression Profile of Stress Response Genes in Apple (Malus domestica) Leaves.

Science.gov (United States)

Wu, Ting; Wang, Yi; Zheng, Yi; Fei, Zhangjun; Dandekar, Abhaya M; Xu, Kenong; Han, Zhenhai; Cheng, Lailiang

2015-09-01

Sorbitol is a major product of photosynthesis in apple (Malus domestica) that is involved in carbohydrate metabolism and stress tolerance. However, little is known about how the global transcript levels in apple leaves respond to decreased sorbitol synthesis. In this study we used RNA sequencing (RNA-seq) profiling to characterize the transcriptome of leaves from transgenic lines of the apple cultivar 'Greensleeves' exhibiting suppressed expression of aldose-6-phosphate reductase (A6PR) to gain insights into sorbitol function and the consequences of decreased sorbitol synthesis on gene expression. We observed that, although the leaves of the low sorbitol transgenic lines accumulate higher levels of various primary metabolites, only very limited changes were found in the levels of transcripts associated with primary metabolism. We suggest that this is indicative of post-transcriptional and/or post-translational regulation of primary metabolite accumulation and central carbon metabolism. However, we identified significantly enriched gene ontology terms belonging to the 'stress related process' category in the antisense lines (P-value sorbitol plays a role in the responses of apple trees to abiotic and biotic stresses. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Detonation-synthesis nanodiamonds: synthesis, structure, properties and applications

Energy Technology Data Exchange (ETDEWEB)

Dolmatov, Valerii Yu [Federal State Unitary Enterprise Special Design-Technology Bureau (FSUE SDTB) ' ' Tekhnolog' ' at the St Petersburg State Institute of Technology (Technical University) (Russian Federation)

2007-04-30

The review outlines the theoretical foundations and industrial implementations of modern detonation synthesis of nanodiamonds and chemical purification of the nanodiamonds thus obtained. The structure, key properties and promising fields of application of detonation-synthesis nanodiamonds are considered.

Detonation-synthesis nanodiamonds: synthesis, structure, properties and applications

International Nuclear Information System (INIS)

Dolmatov, Valerii Yu

2007-01-01

The review outlines the theoretical foundations and industrial implementations of modern detonation synthesis of nanodiamonds and chemical purification of the nanodiamonds thus obtained. The structure, key properties and promising fields of application of detonation-synthesis nanodiamonds are considered.

Leucine-rich diet alters the 1H-NMR based metabolomic profile without changing the Walker-256 tumour mass in rats.

Science.gov (United States)

Viana, Laís Rosa; Canevarolo, Rafael; Luiz, Anna Caroline Perina; Soares, Raquel Frias; Lubaczeuski, Camila; Zeri, Ana Carolina de Mattos; Gomes-Marcondes, Maria Cristina Cintra

2016-10-03

Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia). After 21 days feeding Wistar female rats a leucine-rich diet, distributed in L-leucine and LW-leucine Walker-256 tumour-bearing groups, we examined the metabolomic profile of serum and tumour tissue samples and compared them with samples from tumour-bearing rats fed a normal protein diet (C - control; W - tumour-bearing groups). We utilised 1 H-NMR as a means to study the serum and tumour metabolomic profile, tumour proliferation and tumour protein synthesis pathway. Among the 58 serum metabolites examined, we found that 12 were altered in the tumour-bearing group, reflecting an increase in activity of some metabolic pathways related to energy production, which diverted many nutrients toward tumour growth. Despite displaying increased tumour cell activity (i.e., higher Ki-67 and mTOR expression), there were no differences in tumour mass associated with changes in 23 metabolites (resulting from valine, leucine and isoleucine synthesis and degradation, and from the synthesis and degradation of ketone bodies) in the leucine-tumour group. This result suggests that the majority of nutrients were used for host maintenance. A leucine rich-diet, largely used to prevent skeletal muscle loss, did not affect Walker 256 tumour growth and led to metabolomic alterations that may partially explain the positive effects of leucine for the whole tumour-bearing host.

Dopamine synthesis in alcohol drinking-prone and -resistant mouse strains

Science.gov (United States)

Siciliano, Cody A.; Locke, Jason L.; Mathews, Tiffany A.; Lopez, Marcelo F.; Becker, Howard C.; Jones, Sara R.

2017-01-01

Alcoholism is a prevalent and debilitating neuropsychiatric disease, and much effort has been aimed at elucidating the neurobiological mechanisms underlying maladaptive alcohol drinking in an effort to design rational treatment strategies. In preclinical literature, the use of inbred mouse lines has allowed for the examination of ethanol effects across vulnerable and resistant phenotypes. C57BL/6J mice consistently show higher rates of ethanol drinking compared to most mouse strains. Conversely, DBA/2J mice display low rates of ethanol consumption. Given that the reinforcing and rewarding effects of ethanol are thought to be in part mediated by its actions on dopamine neurotransmission, we hypothesized that alcohol-preferring C57BL/6J and alcohol-avoiding DBA/2J mice would display basal differences in dopamine system function. By administering an L-aromatic acid decarboxylase inhibitor and measuring L-Dopa accumulation via high-performance liquid chromatography as a measure of tyrosine hydroxylase activity, we found no difference in dopamine synthesis between mouse strains in the midbrain, dorsal striatum, or ventral striatum. However, we did find that quinpirole-induced inhibition of dopamine synthesis was greater in the ventral striatum of C57BL/6J mice, suggesting increased presynaptic D2-type dopamine autoreceptor sensitivity. To determine whether dopamine synthesis or autoreceptor sensitivity was altered by a history of ethanol, we exposed C57BL/6J mice to one or two weekly cycles of chronic intermittent ethanol (CIE) exposure and withdrawal. We found that there was an attenuation of baseline dopamine synthesis in the ventral striatum after two cycles of CIE. Finally, we examined tissue content of dopamine and dopamine metabolites across recombinant inbred mice bred from a C57BL/6J × DBA/2J cross (BXD). We found that low dopaminergic activity, as indicated by high dopamine/metabolite ratios, was positively correlated with drinking. Together, these findings

Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks׳ gestation in nulliparous women who subsequently develop preeclampsia.

Science.gov (United States)

Mistry, Hiten D; Gill, Carolyn A; Kurlak, Lesia O; Seed, Paul T; Hesketh, John E; Méplan, Catherine; Schomburg, Lutz; Chappell, Lucy C; Morgan, Linda; Poston, Lucilla

2015-01-01

Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc, and manganese have previously been linked to preeclampsia at the time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered before preeclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Predisease plasma samples (15±1 weeks׳ gestation) were obtained from women enrolled in the international Screening for Pregnancy Endpoints (SCOPE) study who subsequently developed preeclampsia (n=244) and from age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, ceruloplasmin concentration and activity, antioxidant capacity, and markers of oxidative stress were measured by colorimetric assays. Sixty-four tag-single-nucleotide polymorphisms (SNPs) within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Plasma copper and ceruloplasmin concentrations were modestly but significantly elevated in women who subsequently developed preeclampsia (both Ppreeclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop preeclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the etiology of preeclampsia. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

DNA synthesis and cell survival after X-irradiation of mammalian cells treated with caffeine or adenine

International Nuclear Information System (INIS)

Griffiths, T.D.; Carpenter, J.G.; Dahle, D.B.

1978-01-01

The expression of the transient depression in the rate of DNA synthesis normally observed after exposure of randomly-dividing Chinese hamster V-79 or Chinese hamster CHO cells to ionizing radiation could be postponed by a post-irradiation treatment with 1.0 to 2.0 mM adenine or 1.5 mM caffeine. Caffeine may exert its effect by creating additional sites for replication in irradiated cells. Cells treated with caffeine or adenine for 2 or 4 hours after exposure to 3000 rad of 300 kVp X-rays exhibited depressed synthesis only after the removal of caffeine or adenine. These alterations in the timing of the X-ray-induced depression of the rate of DNA synthesis had no effect on X-ray-induced cell killing. Although a 4 hour post-irradiation treatment of randomly-dividing Chinese hamster V-79 cells with 1.0 or 2.0 mM caffeine potentiated X-ray-induced cell killing, this reduction in survival was due primarily to effects on cells not in S-phase. (author)

Inhibition of protein synthesis but not β-adrenergic receptors blocks reconsolidation of a cocaine-associated cue memory

OpenAIRE

Dunbar, Amber B.; Taylor, Jane R.

2016-01-01

Previously consolidated memories have the potential to enter a state of lability upon memory recall, during which time the memory can be altered before undergoing an additional consolidation-like process and being stored again as a long-term memory. Blocking reconsolidation of aberrant memories has been proposed as a potential treatment for psychiatric disorders including addiction. Here we investigated of the effect of systemically administering the protein synthesis inhibitor cycloheximide ...

Epigenetic Regulation of Inflammatory Gene Expression in Macrophages by Selenium

Science.gov (United States)

Narayan, Vivek; Ravindra, Kodihalli C.; Liao, Chang; Kaushal, Naveen; Carlson, Bradley A.; Prabhu, K. Sandeep

2014-01-01

Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of pro-inflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium supplementation may regulate inflammatory gene expression at the epigenetic level. The effect of selenium towards histone acetylation was examined in both in vitro and in vivo models of inflammation by chromatin immunoprecipitation (ChIP) assays and immunoblotting. Our results indicated that selenium supplementation, as selenite, decreased acetylation of histone H4 at K12 and K16 in COX-2 and TNF promoters, and of the p65 subunit of the redox sensitive transcription factor NFκB in primary and immortalized macrophages. On the other hand, selenomethionine had a much weaker effect. Selenite treatment of HIV-1 infected human monocytes also significantly decreased the acetylation of H4 at K12 and K16 on the HIV-1 promoter, supporting the downregulation of proviral expression by selenium. A similar decrease in histone acetylation was also seen in the colonic extracts of mice treated with dextran sodium sulfate that correlated well with the levels of selenium in the diet. Bone marrow-derived macrophages from Trspfl/flCreLysM mice that lack expression of selenoproteins in macrophages confirmed the important role of selenoproteins in the inhibition of histone H4 acetylation. Our studies suggest that the ability of selenoproteins to skew the metabolism of arachidonic acid to contribute, in part, to their ability to inhibit histone acetylation. In summary, our studies suggest a new role for selenoproteins in the epigenetic modulation of pro-inflammatory genes. PMID:25458528

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

Science.gov (United States)

Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

2018-03-01

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis.

Science.gov (United States)

Wilson, Fiona A; Suryawan, Agus; Orellana, Renán A; Nguyen, Hanh V; Jeyapalan, Asumthia S; Gazzaneo, Maria C; Davis, Teresa A

2008-10-01

Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.

Structural and biochemical alterations of human diabetic dermis studied by 3H-lysine incorporation and microscopy

International Nuclear Information System (INIS)

Moczar, M.; Allard, R.; Ouzilou, J.; Robert, L.; Pieraggi, M.-T.; Bouissou, H.; Julian, M.

1976-01-01

The alteration of the structural organization of dermal connective tissue was studied by light and electron microscopy and by biochemical techniques in normal human and in diabetic patients using skin biopsies. Part of the tissue was used for light and electron microscopy, the rest was incubated in the presence of 3 H-lysine for four hours. The 3 H-lysine labelled biopsies were submitted to a sequential extraction procedure in order to obtain representative macromolecular fractions containing the matrix macromolecules. The extracts were analyzed for their chemical composition and radioactivity. Electron microscopy revealed microstructural modifications of the fibroblasts, of the collagen and elastic fibers in the diabetic dermis. The incorporation pattern of 3 H-lysine into the macromolecular fractions was different in the normal and diabetic skin biopsies. The percentage of total radioactivity incorporated increased significantly in the 1M CaCl 2 extractable fraction and in the 6M urea extractable fraction and decreased significantly in the collagenase and elastase extracts in diabetic skin biopsy. These results demonstrate the existence of morphological and biochemical alterations in diabetic connective tissue (dermis) reflecting alterations in the relative rates of synthesis and/or degradation of the intercellular matrix macromolecules as well as of their microarchitectural arrangement

Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

Science.gov (United States)

Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

2015-04-01

The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

Science.gov (United States)

Cao, Nan; Li, Wanyan; Li, Bingxin; Tian, Yunbo; Xu, Danning

2017-12-01

The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese. © 2017 Japanese Society of Animal Science.

N-acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis.

Science.gov (United States)

Yi, Dan; Hou, Yongqing; Wang, Lei; Long, Minhui; Hu, Shengdi; Mei, Huimin; Yan, Liqiong; Hu, Chien-An Andy; Wu, Guoyao

2016-02-01

Dietary supplementation with N-acetylcysteine (NAC) has been reported to improve intestinal health and treat gastrointestinal diseases. However, the underlying mechanisms are not fully understood. According to previous reports, NAC was thought to exert its effect through glutathione synthesis. This study tested the hypothesis that NAC enhances enterocyte growth and protein synthesis independently of cellular glutathione synthesis. Intestinal porcine epithelial cells were cultured for 3 days in Dulbecco's modified Eagle medium containing 0 or 100 μM NAC. To determine a possible role for GSH (the reduced form of glutathione) in mediating the effect of NAC on cell growth and protein synthesis, additional experiments were conducted using culture medium containing 100 μM GSH, 100 μM GSH ethyl ester (GSHee), diethylmaleate (a GSH-depletion agent; 10 μM), or a GSH-synthesis inhibitor (buthionine sulfoximine, BSO; 20 μM). NAC increased cell proliferation, GSH concentration, and protein synthesis, while inhibiting proteolysis. GSHee enhanced cell proliferation and GSH concentration without affecting protein synthesis but inhibited proteolysis. Conversely, BSO or diethylmaleate reduced cell proliferation and GSH concentration without affecting protein synthesis, while promoting protein degradation. At the signaling level, NAC augmented the protein abundance of total mTOR, phosphorylated mTOR, and phosphorylated 70S6 kinase as well as mRNA levels for mTOR and p70S6 kinase in IPEC-1 cells. Collectively, these results indicate that NAC upregulates expression of mTOR signaling proteins to stimulate protein synthesis in enterocytes independently of GSH generation. Our findings provide a hitherto unrecognized biochemical mechanism for beneficial effects of NAC in intestinal cells.

Modelling glass alteration in an altered argillaceous environment

International Nuclear Information System (INIS)

Bildstein, O.; Trotignon, L.; Pozo, C.; Jullien, M.

2007-01-01

The long term behaviour of materials such as glass, steel and clay has been investigated in the context of deep geological disposal of radioactive wastes. The interactions between vitrified wastes, canister corrosion products (CPs) and clay are studied using a modified version of the reaction-transport code Crunch, especially looking at pH changes and possible cementation at the interface with the clayey materials. These perturbations may indeed affect the lifetime of glass matrix in deep repositories, e.g., high pH enhances the rate of glass alteration. This work focuses on the argillite of Bure. The calculations were performed at 323 K with a glass alteration rate switching from a high initial rate to a residual rate according to the sorption capacity of CPs. The time at which this sorption capacity is saturated is crucial to the system in terms of wastes package lifetime. The results show that the glass alteration imposes a high pH value at the interface with CPs and clay: up to a value of 9.2, compared to 7.3 which is the initial pH value in the argillite. Experimental data show that the rate of glass alteration is much higher in such pH conditions. For a R7T7-type glass, the rate is about five times higher at pH 9 than at pH 7. This pH perturbation migrates through the clayey domain as a result of the migration of mobile elements such as boron and sodium, and despite the existence of strong pH buffers in the argillite. The cementation of porosity at the interface between glass and clay is predicted by the model due to the massive precipitation of iron corrosion products and glass alteration products. At this point of the evolution of the system, the pH starts to decrease and the alteration rate of the glass could be significantly reduced. This porosity clogging effect is difficult to confirm by experiments especially since existing data on short term experiments tend to show a pervasive precipitation of silica in the domain instead of a localized precipitation

Biomimetic Synthesis of Gelatin Polypeptide-Assisted Noble-Metal Nanoparticles and Their Interaction Study

Science.gov (United States)

Liu, Ying; Liu, Xiaoheng; Wang, Xin

2011-12-01

Herein, the generation of gold, silver, and silver-gold (Ag-Au) bimetallic nanoparticles was carried out in collagen (gelatin) solution. It first showed that the major ingredient in gelatin polypeptide, glutamic acid, acted as reducing agent to biomimetically synthesize noble metal nanoparticles at 80°C. The size of nanoparticles can be controlled not only by the mass ratio of gelatin to gold ion but also by pH of gelatin solution. Interaction between noble-metal nanoparticles and polypeptide has been investigated by TEM, UV-visible, fluorescence spectroscopy, and HNMR. This study testified that the degradation of gelatin protein could not alter the morphology of nanoparticles, but it made nanoparticles aggregated clusters array (opposing three-dimensional α-helix folding structure) into isolated nanoparticles stabilized by gelatin residues. This is a promising merit of gelatin to apply in the synthesis of nanoparticles. Therefore, gelatin protein is an excellent template for biomimetic synthesis of noble metal/bimetallic nanoparticle growth to form nanometer-sized device.

A Viral RNA Structural Element Alters Host Recognition of Nonself RNA

Energy Technology Data Exchange (ETDEWEB)

Hyde, J. L.; Gardner, C. L.; Kimura, T.; White, J. P.; Liu, G.; Trobaugh, D. W.; Huang, C.; Tonelli, M.; Paessler, S.; Takeda, K.; Klimstra, W. B.; Amarasinghe, G. K.; Diamond, M. S.

2014-01-30

Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.

Transcriptomic responses of the liver and adipose tissues to altered carbohydrate-fat ratio in diet: an isoenergetic study in young rats.

Science.gov (United States)

Tanaka, Mitsuru; Yasuoka, Akihito; Shimizu, Manae; Saito, Yoshikazu; Kumakura, Kei; Asakura, Tomiko; Nagai, Toshitada

2017-01-01

To elucidate the effects of altered dietary carbohydrate and fat balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H) containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45 in energy percent, respectively). The rats consumed the diets for 9 weeks and were subjected to biochemical and DNA microarray analyses. The rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher liver TG and cholesterol content than rats in the L-group. The analysis of differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene ontology analysis of these L vs H DEGs indicated that those related to fatty acid synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These reversed liver DEGs included M-up/H-down genes ( Sds for gluconeogenesis from amino acids) and M-down/H-up genes ( Gpd2 for gluconeogenesis from glycerol, Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation and synthesis of fatty acids were inhibited in these tissues. These results indicate that the alteration of dietary C-F balance differentially affects the transcriptomes of metabolizing and energy-storing tissues.

Distributed PROMPT-LTL Synthesis

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Swen Jacobs

2016-09-01

Full Text Available We consider the synthesis of distributed implementations for specifications in Prompt Linear Temporal Logic (PROMPT-LTL, which extends LTL by temporal operators equipped with parameters that bound their scope. For single process synthesis it is well-established that such parametric extensions do not increase worst-case complexities. For synchronous systems, we show that, despite being more powerful, the distributed realizability problem for PROMPT-LTL is not harder than its LTL counterpart. For asynchronous systems we have to consider an assume-guarantee synthesis problem, as we have to express scheduling assumptions. As asynchronous distributed synthesis is already undecidable for LTL, we give a semi-decision procedure for the PROMPT-LTL assume-guarantee synthesis problem based on bounded synthesis.

Organic synthesis

International Nuclear Information System (INIS)

Lallemand, J.Y.; Fetizon, M.

1988-01-01

The 1988 progress report of the Organic Synthesis Chemistry laboratory (Polytechnic School, France), is presented. The laboratory activities are centered on the chemistry of natural products, which have a biological activity and on the development of new reactions, useful in the organic synthesis. The research works involve the following domains: the natural products chemistry which are applied in pharmacology, the plants and insects chemistry, the organic synthesis, the radical chemistry new reactions and the bio-organic physicochemistry. The published papers, the congress communications and the thesis are listed [fr

Coronavirus minus-strand RNA synthesis and effect of cycloheximide on coronavirus RNA synthesis

International Nuclear Information System (INIS)

Sawicki, S.G.; Sawicki, D.L.

1986-01-01

The temporal sequence of coronavirus plus-strand and minus-strand RNA synthesis was determined in 17CL1 cells infected with the A59 strain of mouse hepatitis virus (MHV). MHV-induced fusion was prevented by keeping the pH of the medium below pH 6.8. This had no effect on the MHV replication cycle, but gave 5- to 10-fold-greater titers of infectious virus and delayed the detachment of cells from the monolayer which permitted viral RNA synthesis to be studied conveniently until at least 10 h postinfection. Seven species of poly(A)-containing viral RNAs were synthesized at early and late times infection, in nonequal but constant ratios. MHV minus-strand RNA synthesis was first detected at about 3 h after infection and was found exclusively in the viral replicative intermediates and was not detected in 60S single-stranded form in infected cells. Early in the replication cycle, from 45 to 65% of the [ 3 H]uridine pulse-labeled RF core of purified MHV replicative intermediates was in minus-strand RNA. The rate of minus-strand synthesis peaked at 5 to 6 h postinfection and then declined to about 20% of the maximum rate. The addition of cycloheximide before 3 h postinfection prevented viral RNA synthesis, whereas the addition of cycloheximide after viral RNA synthesis had begun resulted in the inhibition of viral RNA synthesis. The synthesis of both genome and subgenomic mRNAs and of viral minus strands required continued protein synthesis, and minis-strand RNA synthesis was three- to fourfold more sensitive to inhibition of cycloheximide than was plus-strand synthesis

Transcriptional Alterations of Virulence-Associated Genes in Extended Spectrum Beta-Lactamase (ESBL-Producing Uropathogenic Escherichia coli during Morphologic Transitions Induced by Ineffective Antibiotics

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Isak Demirel

2017-06-01

Full Text Available It is known that an ineffective antibiotic treatment can induce morphological shifts in uropathogenic Escherichia coli (UPEC but the virulence properties during these shifts remain to be studied. The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL-producing UPEC (ESBL019 during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. Microarray results showed that the different morphological states of ESBL019 had significant transcriptional alterations of a large number of genes (Transition; 7%, Filamentation; 32%, and Reverted 19% of the entities on the array. All three morphological states of ESBL019 were associated with a decreased energy metabolism, altered iron acquisition systems and altered adhesion expression. In addition, genes associated with LPS synthesis and bacterial motility was also altered in all the morphological states. Furthermore, the transition state induced a significantly higher release of TNF-α from bladder epithelial cells compared to all other morphologies, while the reverted state was unable to induce TNF-α release. Our findings show that the morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.

Asymmetric Synthesis of Fluoroamines from Chiral Aziridines

Energy Technology Data Exchange (ETDEWEB)

Park, Hyeonjeong; Yoon, Dooha; Ha, Hyunjoon [Hankuk Univ. of Foreign Studies, Yongin (Korea, Republic of); Son, Se In; Lee, Won Koo [Sogang Univ., Seoul (Korea, Republic of)

2014-03-15

We described an efficient preparation of fluoroamines by the ring-opening reactions of chiral aziridines with Et{sub 3}N·3HF. At most cases both regioisomers were obtained from the ring openings at C2 and C3 positions depending on the substituents at C2 of the starting substrates.The fluorinated organic molecules have attracted great attentions from synthetic and medicinal chemists with wide use of various agrochemicals and pharmaceuticals. Their uniqueness is originated from its electronic characteristics and the small size without altering the molecular conformations of non-fluorinated compounds. The fluorine is the second most widely used atom in the commercial drugs following the amine. Thereby, the elaboration of fluoro-amines bearing two most widely used atoms in drugs is one of the most challenging problems in drug synthesis and its development.

An Approach to Interface Synthesis

DEFF Research Database (Denmark)

Madsen, Jan; Hald, Bjarne

1995-01-01

Presents a novel interface synthesis approach based on a one-sided interface description. Whereas most other approaches consider interface synthesis as optimizing a channel to existing client/server modules, we consider the interface synthesis as part of the client/server module synthesis (which...... may contain the re-use of existing modules). The interface synthesis approach describes the basic transformations needed to transform the server interface description into an interface description on the client side of the communication medium. The synthesis approach is illustrated through a point...

Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

International Nuclear Information System (INIS)

Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P.

2004-01-01

The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

Traumatic brain injury alters methionine metabolism: implications for pathophysiology

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Pramod K Dash

2016-04-01

Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

DEFF Research Database (Denmark)

Vicca, S.; Bahn, M.; Estiarte, M.

2014-01-01

dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is 'no' - as based on the most reliable data sets available. We strongly recommend that future experiments focus more...

Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression.

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Dongsha Wang

Full Text Available The main challenge in addressing the role of DNA methylation in human behaviour is the fact that the brain is inaccessible to epigenetic analysis in living humans. Using positron emission tomography (PET measures of brain serotonin (5-HT synthesis, we found in a longitudinal sample that adult males with high childhood-limited aggression (C-LHPA had lower in vivo 5-HT synthesis in the orbitofrontal cortex (OBFC. Here we hypothesized that 5-HT alterations associated with childhood aggression were linked to differential DNA methylation of critical genes in the 5-HT pathway and these changes were also detectable in peripheral white blood cells. Using pyrosequencing, we determined the state of DNA methylation of SLC6A4 promoter in T cells and monocytes isolated from blood of cohort members (N = 25 who underwent a PET scan, and we examined whether methylation status in the blood is associated with in vivo brain 5-HT synthesis. Higher levels of methylation were observed in both T cells and monocytes at specific CpG sites in the C-LHPA group. DNA methylation of SLC6A4 in monocytes appears to be associated more reliably with group membership than T cells. In both cell types the methylation state of these CpGs was associated with lower in vivo measures of brain 5-HT synthesis in the left and right lateral OBFC (N = 20 where lower 5-HT synthesis in C-LHPA group was observed. Furthermore, in vitro methylation of the SLC6A4 promoter in a luciferase reporter construct suppresses its transcriptional activity supporting a functional role of DNA methylation in SLC6A4 promoter regulation. These findings indicate that state of SLC6A4 promoter methylation is altered in peripheral white blood cells of individuals with physical aggression during childhood. This supports the relevance of peripheral DNA methylation for brain function and suggests that peripheral SLC6A4 DNA methylation could be a marker of central 5-HT function.

Influence of metronidazole on the survival rate of whole-body irradiated mice and on the DNA repair synthesis of lymphocytes

International Nuclear Information System (INIS)

Magdon, E.; Schroeder, E.

1978-01-01

With reference to literature reports the effect of Metronidazole [1-(hydroxyethyl)-5-nitro-2-methyl-imidazole] on the survival rate of C 3 H inbred mice following whole-body doses ranging from 5 to 15 Gy was determined under oxic and hypoxic conditions. Ehrlich ascites tumor cells were used to study the influence of Metronidazole on radiation-induced alterations of the DNA sedimentation behavior in the alkaline sucrose gradient under oxic conditions in vitro. The effect of Metronidazole on the semiconservative DNA synthesis was investigated under oxic and hypoxic conditions in Ehrlich ascites carcinoma cells and L5178Y lymphoma cells. Furthermore, it was examined whether the radiation-induced inhibition of semiconservative DNA synthesis in L5178Y lymphoma cells and the radiation-induced repair synthesis in lymphocytes is influenced by Metronidazole. From the values of the LDsub(50/30) after whole-body irradiation a sensitilization factor of 1.3 was derived for Metronidazole under hypoxic conditions. Under atmospheric conditions an increase of the radiation effect by a factor of 1.1 was obtained. The protective factor of hypoxia was 1.6 and thus greater than the radiosensibilization caused by Metronidazole. The DNA synthesis was slightly inhibited by Metronidazole under both hypoxic and euoxic conditions. The studies revealed no significant influence of Metronidazole on radiation-induced changes of the DNA sedimentation behavior and of the DNA repair synthesis as well as on the radiation induced inhibition of semiconservative DNA synthesis. (author)

Auxin synthesis gene tms1 driven by tuber-specific promoter alters hormonal status of transgenic potato plants and their responses to exogenous phytohormones.

Science.gov (United States)

Kolachevskaya, Oksana O; Sergeeva, Lidiya I; Floková, Kristyna; Getman, Irina A; Lomin, Sergey N; Alekseeva, Valeriya V; Rukavtsova, Elena B; Buryanov, Yaroslav I; Romanov, Georgy A

2017-03-01

Ectopic auxin overproduction in transgenic potato leads to enhanced productivity accompanied with concerted and occasional changes in hormonal status, and causing altered response of transformants to exogenous auxin or cytokinin. Previously, we generated potato transformants expressing Agrobacterium-derived auxin synthesis gene tms1 driven by tuber-specific patatin gene promoter (B33-promoter). Here, we studied the endogenous hormonal status and the response to exogenous phytohormones in tms1 transformants cultured in vitro. Adding indole-3-acetic acid (IAA) or kinetin to culture medium affected differently tuberization of tms1-transformed and control plants, depending also on sucrose content in the medium. Exogenous phytohormones ceased to stimulate the tuber initiation in transformants at high (5-8%) sucrose concentration, while in control plants the stimulation was observed in all experimental settings. Furthermore, exogenous auxin partly inhibited the tuber initiation, and exogenous cytokinin reduced the average tuber weight in most transformants at high sucrose content. The elevated auxin level in tubers of the transformants was accompanied with a decrease in content of cytokinin bases and their ribosides in tubers and most shoots. No concerted changes in contents of abscisic, jasmonic, salicylic acids and gibberellins in tubers were detected. The data on hormonal status indicated that the enhanced productivity of tms1 transformants was due to auxin and not mediated by other phytohormones. In addition, exogenous cytokinin was shown to upregulate the expression of genes encoding orthologs of auxin receptors. Overall, the results showed that tms1 expression and local increase in IAA level in transformants affect both the balance of endogenous cytokinins and the dynamics of tuberization in response to exogenous hormones (auxin, cytokinin), the latter reaction depending also on the carbohydrate supply. We introduce a basic model for the hormonal network

Matrix Production, Pigment Synthesis, and Sporulation in a Marine Isolated Strain of Bacillus pumilus.

Science.gov (United States)

Di Luccia, Blanda; Riccio, Antonio; Vanacore, Adele; Baccigalupi, Loredana; Molinaro, Antonio; Ricca, Ezio

2015-10-21

The ability to produce an extracellular matrix and form multicellular communities is an adaptive behavior shared by many bacteria. In Bacillus subtilis, the model system for spore-forming bacteria, matrix production is one of the possible differentiation pathways that a cell can follow when vegetative growth is no longer feasible. While in B. subtilis the genetic system controlling matrix production has been studied in detail, it is still unclear whether other spore formers utilize similar mechanisms. We report that SF214, a pigmented strain of Bacillus pumilus isolated from the marine environment, can produce an extracellular matrix relying on orthologs of many of the genes known to be important for matrix synthesis in B. subtilis. We also report a characterization of the carbohydrates forming the extracellular matrix of strain SF214. The isolation and characterization of mutants altered in matrix synthesis, pigmentation, and spore formation suggest that in strain SF214 the three processes are strictly interconnected and regulated by a common molecular mechanism.

Circadian rhythm genes mediate fenvalerate-induced inhibition of testosterone synthesis in mouse Leydig cells.

Science.gov (United States)

Guo, Yichen; Shen, Ouxi; Han, Jingjing; Duan, Hongyu; Yang, Siyuan; Zhu, Zhenghong; Tong, Jian; Zhang, Jie

2017-01-01

Fenvalerate (Fen), a widely used pesticide, is known to impair male reproductive functions by mechanisms that remain to be elucidated. Recent studies indicated that circadian clock genes may play an important role in successful male reproduction. The aim of this study was to determine the effects of Fen on circadian clock genes involved in the biosynthesis of testosterone using TM3 cells derived from mouse Leydig cells. Data demonstrated that the circadian rhythm of testosterone synthesis in TM3 cells was disturbed following Fen treatment as evidenced by changes in the circadian rhythmicity of core clock genes (Bmal1, Rev-erbα, Rorα). Further, the observed altered rhythms were accompanied by increased intracellular Ca 2+ levels and modified steroidogenic acute regulatory (StAR) mRNA expression. Thus, data suggested that Fen inhibits testosterone synthesis via pathways involving intracellular Ca 2+ and clock genes (Bmal1, Rev-Erbα, Rorα) as well as StAR mRNA expression in TM3 cells.

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

Science.gov (United States)

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum

Science.gov (United States)

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

Directory of Open Access Journals (Sweden)

Elke Humer

Full Text Available A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10, medium (n = 8, and high (n = 12 lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum

International Nuclear Information System (INIS)

Westfall, T.C.; Besson, M.J.; Giorguieff, M.F.; Glowinski, J.

1976-01-01

Striatal slices were continuously superfused with L-3,5- 3 H-Tyrosine(50μCi/ml) and 3 H-H 2 O [index of 3 H-dopamine ( 3 H-DA) synthesis] and 3 H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k + for 7.5 min induced a marked increase in 3 H-DA release and a biphasic effect on synthesis. The decrease in the rate of 3 H-H 2 O formation induced by K + was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3 H-DA uptake (10 -6 M) it potentiated 3 H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10 -6 M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10 -6 M) significantly prevented the decrease in 3 H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter. (orig.) [de

Altered expression of glycosaminoglycans in metastatic 13762NF rat mammary adenocarcinoma cells

International Nuclear Information System (INIS)

Steck, P.A.; Cheong, P.H.; Nakajima, M.; Yung, W.K.A.; Moser, R.P.; Nicolson, G.L.

1987-01-01

A difference in the expression and metabolism of [ 35 S]sulfated glycosaminoglycans between rat mammary tumor cells derived from a primary tumor and those from its metastatic lesions has been observed. Cells from the primary tumor possessed about equal quantities of chondroitin sulfate and heparan sulfate on their cell surfaces but released fourfold more chondroitin sulfate than heparan sulfate into their medium. In contrast, cells from distal metastatic lesions expressed approximately 5 times more heparan sulfate than chondroitin sulfate in both medium and cell surface fractions. This was observed to be the result of differential synthesis of the glycosaminoglycans and not of major structural alterations of the individual glycosaminoglycans. The degree of sulfation and size of heparan sulfate were similar for all cells examined. However, chondroitin sulfate, observed to be only chondroitin 4-sulfate, from the metastases-derived cells had a smaller average molecular weight on gel filtration chromatography and showed a decreased quantity of sulfated disaccharides upon degradation with chondroitin ABC lyase compared to the primary tumor derived cells. Major qualitative or quantitative alterations were not observed for hyaluronic acid among the various 13762NF cells. The metabolism of newly synthesized sulfated glycosaminoglycans was also different between cells from primary tumor and metastases. A pulse-chase kinetics study demonstrated that both heparan sulfate and chondroitin sulfate were degraded by the metastases-derived cells, whereas the primary tumor derived cells degraded only heparan sulfate and degraded it at a slower rate. These results suggested that altered glycosaminoglycan expression and metabolism may be associated with the metastatic process in 13762NF rat mammary tumor cells

Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

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Gillian W Reierson

2009-09-01

Full Text Available Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyclic adenosine monophosphate (cAMP signaling cascade and of arylalkylamine N-acetyltransferase (AA-NAT, the rate-limiting enzyme for its synthesis. Cyclic AMP is synthesized by adenylate cyclases (AC and degraded by phosphodiesterases (PDEs. Little is known about the contribution of the PDE system to antidepressant-induced alterations in pineal cAMP signaling and melatonin synthesis. In the present study we used enzyme immunoassay to measure plasma melatonin levels and pineal cAMP levels and as well as quantitative real-time polymerase chain reaction to measure pineal expression of PDE, AC, and AA-NAT genes in rats chronically treated with the prototypic antidepressant fluoxetine. We found elevated melatonin synthesis with increased pineal AA-NAT gene expression and daytime plasma melatonin levels and downregulated cAMP signaling with increased PDE and unchanged AC pineal gene expression, and decreased content of pineal cAMP. We conclude that chronic fluoxetine treatment increases daytime plasma melatonin and pineal AA-NAT gene expression despite downregulated pineal cAMP signaling in the rodent.Keywords: antidepressant, melatonin, pineal, nucleotides, cyclic, phosphodiesterase, rat

Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA

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Cases, Olivier; Grimsby, Joseph; Gaspar, Patricia; Chen, Kevin; Pournin, Sandrine; Müller, Ulrike; Aguet, Michel; Babinet, Charles; Shih, Jean Chen; De Maeyer, Edward

2010-01-01

Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males. PMID:7792602

Structure-based synthesis from natural products to drug prototypes

International Nuclear Information System (INIS)

Hanessian, S.

2009-01-01

X-Ray crystallographic data available from complexes of natural and synthetic molecules with the enzyme thrombin has aided to the design and synthesis of truncated and hybrid molecules exhibiting excellent inhibition in vitro. The vital importance of natural products for the well-being of man has been known lor millennia. Their therapeutic benefits to alleviate pain or cure diseases continue to rank natural products among the primary sources of potential drugs. Great advances have been made in the methods of isolation, identification, and structure elucidation of some of the most complex natural products in recent years. The advent of molecular biology and genetic mapping has also aided in our understanding of the intriguing biosynthetic pathways leading to various classes of therapeutically relevant antibiotic, anticancer, and related natural products. Elegant and practical methodology has been developed leading to the total synthesis of virtually every class of medicinally important natural product. In some cases, natural products or their chemically modified congeners have been manufactured by total synthesis on an industrial level which is a testament to the ingenuity of process chemists. In spite of their potent activities HI enzymatic ox receptor-mediated assays, not all natural products are amenable to being developed as marketable drags. In many instances unfavorable pharmacological effects cannot be overcome without drastic structural and functional modifications, which may also result in altered efficacy. Structure modification through truncation, functional group variations, isosteric replacements, and skeletal rigidifications aided by molecular modeling, X ray crystallography of protein targets, or NMR data are valid objectives in the context of small molecule drug discovery starting with bioactive natural products. A large proportion of these pertain to chemotherapeutic agents against cancer

In situ enzymology of DNA replication and ultraviolet-induced DNA repair synthesis in permeable human cells

International Nuclear Information System (INIS)

Dresler, S.; Frattini, M.G.; Robinson-Hill, R.M.

1988-01-01

Using permeable diploid human fibroblasts, the authors have studied the deoxyribonucleoside triphosphate concentration dependences of ultraviolet- (UV-) induced DNA repair synthesis and semiconservative DNA replication. In both cell types (AG1518 and IMR-90) examined, the apparent K m values for dCTP, dGTP, and dTTP for DNA replication were between 1.2 and 2.9 μM. For UV-induced DNA repair synthesis, the apparent K m values were substantially lower, ranging from 0.11 to 0.44 μM for AG1518 cells and from 0.06 to 0.24 μM for IMR-90 cells. Recent data implicate DNA polymerase δ in UV-induced repair synthesis and suggest that DNA polymerases α and δ are both involved in semiconservative replication. They measured K m values for dGTP and dTTP for polymerases α and δ, for comparison with the values for replication and repair synthesis. The deoxyribonucleotide K m values for DNA polymerase δ are much greater than the K m values for UV-induced repair synthesis, suggesting that when polymerase δ functions in DNA repair, its characteristics are altered substantially either by association with accessory proteins or by direct posttranslational modification. In contrast, the deoxyribonucleotide binding characteristics of the DNA replication machinery differ little from those of the isolated DNA polymerases. The K m values for UV-induced repair synthesis are 5-80-fold lower than deoxyribonucleotide concentrations that have been reported for intact cultured diploid human fibroblasts. For replication, however, the K m for dGTP is only slightly lower than the average cellular dGTP concentration that has been reported for exponentially growing human fibroblasts. This finding is consistent with the concept that nucleotide compartmentation is required for the attainment of high rates of DNA replication in vivo

Direct synthesis of 2-methyl-1-propanol/methanol fuels and feedstocks: Quarterly technical progress report for the period June--August 1985

Energy Technology Data Exchange (ETDEWEB)

Klier, K.; Herman, R. G.; Simmons, G. W.; Nunan, J.; Himelfarb, P. B.

1985-09-01

During the present quarter, and intensive series of aluminum- supported catalysts, both Cs promoted and unpromoted, have been prepared by a special preparation technique and tested to determine alcohol synthesis activity, selectivities, and stability. Preparation of a single-phase hydrotalcite-like ((Cu/sub x/Zn/sub 1 -x/)/sub 6/Al/sub 2/CO/sub 3/(OH)/sub 16//center dot/4H/sub 2/O) catalyst precursor has been successfully accomplished. Some of these catalysts have been tested to determine their activities in producing methanol and higher alcohols. It has been observed that catalysts obtained by calcination and reduction of the hydrotalcite-like precursor are very active methanol synthesis catalysts. Doping these catalysts with cesium in an aqueous solution leads to initial deactivation, which is partially recovered by doping at higher cesium levels. Results give us guidelines for altering the promoter doping procedure so that a more active and selective aluminum-supported higher alcohol synthesis catalyst will be obtained. 4 refs., 13 figs., 13 tabs.

Equivalence Checking between Pre-synthesis and Post-synthesis Programs by Using VIS

Energy Technology Data Exchange (ETDEWEB)

Lee, Jonghoon; Yoo, Junbeom [Konkuk Univ., Seoul (Korea, Republic of); Choi, Jonggyun; Lee, Jangsoo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

PLC (Programmable Logic Controller)-based Software development, the design programs are translated into implementation programs, and behavioral equivalence between the design and implementation is demonstrated by formal method based technique. In FPGA-based software development, the design programs are also synthesized into implementation programs. However, in this process, testing and simulation based comparison techniques are mainly used. This paper proposes a formal method based technique to demonstrate behavioral equivalence between pre-synthesis and post-synthesis programs with VIS (Verification Interacting with Synthesis) verification system. We translated into BLIF-MV which is front-end of VIS, from Verlag and EDIF net list which synthesized from the same Verlag by an automatic synthesis tool. This paper proposes a formal method based technique to confirm correctness of synthesis by using equivalence checking of VIS verification system. In order to confirm the effectiveness of the proposed technique, we performed a case study with a part of prototype version of the RPS BP, and demonstrated a behavioral equivalence between Verlag HDL and EDIF post-synthesis net list.

Equivalence Checking between Pre-synthesis and Post-synthesis Programs by Using VIS

International Nuclear Information System (INIS)

Lee, Jonghoon; Yoo, Junbeom; Choi, Jonggyun; Lee, Jangsoo

2013-01-01

PLC (Programmable Logic Controller)-based Software development, the design programs are translated into implementation programs, and behavioral equivalence between the design and implementation is demonstrated by formal method based technique. In FPGA-based software development, the design programs are also synthesized into implementation programs. However, in this process, testing and simulation based comparison techniques are mainly used. This paper proposes a formal method based technique to demonstrate behavioral equivalence between pre-synthesis and post-synthesis programs with VIS (Verification Interacting with Synthesis) verification system. We translated into BLIF-MV which is front-end of VIS, from Verlag and EDIF net list which synthesized from the same Verlag by an automatic synthesis tool. This paper proposes a formal method based technique to confirm correctness of synthesis by using equivalence checking of VIS verification system. In order to confirm the effectiveness of the proposed technique, we performed a case study with a part of prototype version of the RPS BP, and demonstrated a behavioral equivalence between Verlag HDL and EDIF post-synthesis net list

Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

Science.gov (United States)

2011-01-01

Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) S. aureus strains. Methods Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry. Results Growth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σB), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σB-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to DcRS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation. Conclusions The results of

Alteration of consciousness in focal epilepsy: the global workspace alteration theory.

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Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel

2014-01-01

Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.

Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

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Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

2013-03-01

The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

On the pathologically altered pulmonary pattern

International Nuclear Information System (INIS)

Ginzburg, M.A.; Kinoshenko, Yu.T.

1982-01-01

The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

Regulation of pro-adrenocorticotropin-endorphin synthesis and secretion in cultured neonatal rat anterior pituitary

Energy Technology Data Exchange (ETDEWEB)

Sato, S.M.; Mains, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

1987-08-01

Previous work demonstrated that newborn rat anterior pituitary corticotropes display processing patterns for pro-ACTH/endorphin that are different from the adult. The synthesis and release of beta-endorphin-related peptides was examined in dispersed cell and explant cultures of newborn anterior pituitary to investigate corticotrope development further. The temporal pattern of pro-ACTH/endorphin processing differed significantly from adult rat melanotropes and AtT-20 cells. While pro-ACTH/endorphin processing begins within 30 min of synthesis in adult melanotropes and AtT-20 cells, pulse-labeling of newborn corticotropes in culture indicated that pro-ACTH/endorphin remained uncleaved for at least 90 min after synthesis. With further incubation, there was a decrease in radioactivity associated with the precursor and an equivalent rise in the radioactivity associated with beta-endorphin and beta-lipotropin. However, unprocessed precursor still remained in the cultured newborn anterior pituitary cells after a 25-h chase. Although intact pro-ACTH/endorphin from newborn corticotropes was very long-lived, the precursor did undergo oligosaccharide maturation and became endoglycosidase H resistant within 1 h after synthesis. Similar to the adult, pro-ACTH/endorphin synthesis was doubled in cultures of newborn anterior pituitary chronically treated with 10 nM CRF resulting in a 3- to 4-fold stimulation of secretion over the basal rate. However, unlike the AtT-20 cell or adult rat corticotrope, the proteolytic processing of pro-ACTH/endorphin in the newborn corticotrope was altered by chronic secretagogue treatment; less pro-ACTH/endorphin was converted to beta-endorphin in secretagogue-treated corticotropes than in controls. Thus processing of pro-ACTH/endorphin in the corticotrope is not mature by birth and can be regulated by chronic CRF treatment.

Regulation of pro-adrenocorticotropin-endorphin synthesis and secretion in cultured neonatal rat anterior pituitary

International Nuclear Information System (INIS)

Sato, S.M.; Mains, R.E.

1987-01-01

Previous work demonstrated that newborn rat anterior pituitary corticotropes display processing patterns for pro-ACTH/endorphin that are different from the adult. The synthesis and release of beta-endorphin-related peptides was examined in dispersed cell and explant cultures of newborn anterior pituitary to investigate corticotrope development further. The temporal pattern of pro-ACTH/endorphin processing differed significantly from adult rat melanotropes and AtT-20 cells. While pro-ACTH/endorphin processing begins within 30 min of synthesis in adult melanotropes and AtT-20 cells, pulse-labeling of newborn corticotropes in culture indicated that pro-ACTH/endorphin remained uncleaved for at least 90 min after synthesis. With further incubation, there was a decrease in radioactivity associated with the precursor and an equivalent rise in the radioactivity associated with beta-endorphin and beta-lipotropin. However, unprocessed precursor still remained in the cultured newborn anterior pituitary cells after a 25-h chase. Although intact pro-ACTH/endorphin from newborn corticotropes was very long-lived, the precursor did undergo oligosaccharide maturation and became endoglycosidase H resistant within 1 h after synthesis. Similar to the adult, pro-ACTH/endorphin synthesis was doubled in cultures of newborn anterior pituitary chronically treated with 10 nM CRF resulting in a 3- to 4-fold stimulation of secretion over the basal rate. However, unlike the AtT-20 cell or adult rat corticotrope, the proteolytic processing of pro-ACTH/endorphin in the newborn corticotrope was altered by chronic secretagogue treatment; less pro-ACTH/endorphin was converted to beta-endorphin in secretagogue-treated corticotropes than in controls. Thus processing of pro-ACTH/endorphin in the corticotrope is not mature by birth and can be regulated by chronic CRF treatment

Green tea polyphenols alter lipid metabolism in the livers of broiler chickens through increased phosphorylation of AMP-activated protein kinase.

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Jinbao Huang

Full Text Available Our previous results showed that green tea polyphenols (GTPs significantly altered the expression of lipid-metabolizing genes in the liver of chickens. However, the underlying mechanism was not elucidated. In this study, we further characterized how GTPs influence AMP-activated protein kinase (AMPK in the regulation of hepatic fat metabolism. Thirty-six male chickens were fed GTPs at a daily dose of 0, 80 or 160 mg/kg of body weight for 4 weeks. The results demonstrated that oral administration of GTPs significantly reduced hepatic lipid content and abdominal fat mass, enhanced the phosphorylation levels of AMPKα and ACACA, and altered the mRNA levels and enzymatic activities of lipid-metabolizing enzymes in the liver. These results suggested that the activation of AMPK is a potential mechanism by which GTPs regulate hepatic lipid metabolism in such a way that lipid synthesis is reduced and fat oxidation is stimulated.

Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

Science.gov (United States)

Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

2012-09-19

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids.

Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

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Johann eSteiner

2014-11-01

Full Text Available Clozapine has stronger systemic metabolic side effects than haloperidol and it was hypothesized that therapeutic antipsychotic and adverse metabolic effects might be related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production.Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT and monocarboxylate (MCT transporters was determined after 6h and 24h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed.Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside.Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study

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Subit Barua

2015-01-01

Full Text Available Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

Altered minor-groove hydrogen bonds in DNA block transcription elongation by T7 RNA polymerase.

Science.gov (United States)

Tanasova, Marina; Goeldi, Silvan; Meyer, Fabian; Hanawalt, Philip C; Spivak, Graciela; Sturla, Shana J

2015-05-26

DNA transcription depends upon the highly efficient and selective function of RNA polymerases (RNAPs). Modifications in the template DNA can impact the progression of RNA synthesis, and a number of DNA adducts, as well as abasic sites, arrest or stall transcription. Nonetheless, data are needed to understand why certain modifications to the structure of DNA bases stall RNA polymerases while others are efficiently bypassed. In this study, we evaluate the impact that alterations in dNTP/rNTP base-pair geometry have on transcription. T7 RNA polymerase was used to study transcription over modified purines and pyrimidines with altered H-bonding capacities. The results suggest that introducing wobble base-pairs into the DNA:RNA heteroduplex interferes with transcriptional elongation and stalls RNA polymerase. However, transcriptional stalling is not observed if mismatched base-pairs do not H-bond. Together, these studies show that RNAP is able to discriminate mismatches resulting in wobble base-pairs, and suggest that, in cases of modifications with minor steric impact, DNA:RNA heteroduplex geometry could serve as a controlling factor for initiating transcription-coupled DNA repair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrated biofuels process synthesis

DEFF Research Database (Denmark)

Torres-Ortega, Carlo Edgar; Rong, Ben-Guang

2017-01-01

Second and third generation bioethanol and biodiesel are more environmentally friendly fuels than gasoline and petrodiesel, andmore sustainable than first generation biofuels. However, their production processes are more complex and more expensive. In this chapter, we describe a two-stage synthesis......% used for bioethanol process), and steam and electricity from combustion (54%used as electricity) in the bioethanol and biodiesel processes. In the second stage, we saved about 5% in equipment costs and 12% in utility costs for bioethanol separation. This dual synthesis methodology, consisting of a top......-level screening task followed by a down-level intensification task, proved to be an efficient methodology for integrated biofuel process synthesis. The case study illustrates and provides important insights into the optimal synthesis and intensification of biofuel production processes with the proposed synthesis...

Inhibition of protein synthesis but not β-adrenergic receptors blocks reconsolidation of a cocaine-associated cue memory.

Science.gov (United States)

Dunbar, Amber B; Taylor, Jane R

2016-08-01

Previously consolidated memories have the potential to enter a state of lability upon memory recall, during which time the memory can be altered before undergoing an additional consolidation-like process and being stored again as a long-term memory. Blocking reconsolidation of aberrant memories has been proposed as a potential treatment for psychiatric disorders including addiction. Here we investigated of the effect of systemically administering the protein synthesis inhibitor cycloheximide or the β-adrenergic antagonist propranolol on reconsolidation. Rats were trained to self-administer cocaine, during which each lever press resulted in the presentation of a cue paired with an intravenous infusion of cocaine. After undergoing lever press extinction to reduce operant responding, the cue memory was reactivated and rats were administered systemic injections of propranolol, cycloheximide, or vehicle. Post-reactivation cycloheximide, but not propranolol, resulted in a reactivation-dependent decrease in cue-induced reinstatement, indicative of reconsolidation blockade by protein synthesis inhibition. The present data indicate that systemically targeting protein synthesis as opposed to the β-adrenergic system may more effectively attenuate the reconsolidation of a drug-related memory and decrease drug-seeking behavior. © 2016 Dunbar and Taylor; Published by Cold Spring Harbor Laboratory Press.

Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: Evidence for differential gene expression

International Nuclear Information System (INIS)

Kim, Sunyoung; Baltimore, D.; Byrn, R.; Groopman, J.

1989-01-01

The kinetics of retroviral DNA and RNA synthesis are parameters vital to understanding viral growth, especially for human immunodeficiency virus (HIV), which encodes several of its own regulatory genes. The authors have established a single-cycle growth condition for HIV in H9 cells, a human CD4 + lymphocyte line. The full-length viral linear DNA is first detectable by 4 h postinfection. During a one-step growth of HIV, amounts of viral DNA gradually increase until 8 to 12 h postinfection and then decrease. The copy number of unintegrated viral DNA is not extraordinarily high even at its peak. Most strikingly, there is a temporal program of RNA accumulation: the earliest RNA is greatly enriched in the 2-kilobase subgenomic mRNA species, while the level of 9.2-kilobase RNA which is both genomic RNA and mRNA remains low until after 24 h of infection. Virus production begins at about 24 h postinfection. Thus, viral DNA synthesis is as rapid as for other retroviruses, but viral RNA synthesis involves temporal alteration in the species that accumulate, presumably as a consequence of viral regulatory genes

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

Science.gov (United States)

Perry, Ben D; Rahnert, Jill A; Xie, Yang; Zheng, Bin; Woodworth-Hobbs, Myra E; Price, S Russ

2018-01-01

Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

Role of presynaptic receptors in the release and synthesis of /sup 3/H-dopamine by slices of rat striatum

Energy Technology Data Exchange (ETDEWEB)

Westfall, T C; Besson, M J; Giorguieff, M F; Glowinski, J [Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France). Groupe de Neuropharmacologie Biochimique

1976-01-01

Striatal slices were continuously superfused with L-3,5-/sup 3/H-Tyrosine(50..mu..Ci/ml) and /sup 3/H-H/sub 2/O (index of /sup 3/H-dopamine (/sup 3/H-DA) synthesis) and /sup 3/H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k/sup +/ for 7.5 min induced a marked increase in /sup 3/H-DA release and a biphasic effect on synthesis. The decrease in the rate of /sup 3/H-H/sub 2/O formation induced by K/sup +/ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked /sup 3/H-DA uptake (10/sup -6/M) it potentiated /sup 3/H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10/sup -6/M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10/sup -6/M) significantly prevented the decrease in /sup 3/H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter.

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

Directory of Open Access Journals (Sweden)

Ben D Perry

Full Text Available Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4. Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides, palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242. Inflammatory indicators of TLR4 activation (IL-6 and TNFα and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

Enantioselective biotransformations of nitriles in organic synthesis.

Science.gov (United States)

Wang, Mei-Xiang

2015-03-17

other methods. Nitrile substrates are readily available, and the mild reaction conditions are specific toward cyano and amido functional groups without interfering with other reactive functional groups. I anticipate that further advances in this field will lead to new and engineered nitrile-hydrolyzing enzymes or catalytic systems with improved activity and altered selectivity. These advances will broaden the scope of these transformations and their applications in organic synthesis.

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

Science.gov (United States)

Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

2009-12-01

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

Dose- and time-dependent radiation inhibition of RNA and glycosaminoglycan synthesis in embryonic cartilage: an in vitro study

Energy Technology Data Exchange (ETDEWEB)

Cornelissen, M.; Thierens, H.; De Ridder, L. (Ghent Rijksuniversiteit (Belgium))

1990-05-01

Radiation effects on the RNA and glycosaminoglycan (GAG) synthesis of embryonic cartilaginous tibiae were studied in vitro during a 4- or 7-day culture period. Before culture, tibiae received single radiation doses of 20, 50 or 100 Gy. A limited, dose-dependent immediate effect on RNA and GAG synthesis was found. This effect was unchanged for 2 days. After this period a time-dependent delayed effect was observed. For each radiation dose, and for each precursor, the same time-related pattern was found. At the end of the culture period acid phosphatase activity, an early indicator of apoptosis, was higher in irradiated tibiae than in controls. No other morphological ultrastructural differences were observed at this time. The authors conclude that metabolic alterations are probably due to stimulation of initial stages of the apoptotic process in the irradiated cartilage cells. (author).

Effects of inhibitors of DNA synthesis and protein synthesis on the rate of DNA synthesis after exposure of mammalian cells to ultraviolet light

International Nuclear Information System (INIS)

Griffiths, T.D.; Dahle, D.B.; Meechan, P.J.; Carpenter, J.G.

1981-01-01

Chinese hamster V-79 cells were treated with metabolic inhibitors of DNA or protein synthesis for various intervals of time after exposure of 3.0 or 5.0 J m -2 . After removal of the metabolic block(s) the rate of DNA synthesis was followed by measuring the incorporation of [ 14 C]thymidine into acid-insoluble material. A 2.5 or 5.0h incubation with cycloheximide or hydroxyurea was effective in delaying the onset of the recovery in the rate of DNA synthesis that normally becomes evident several hours after exposure to ultraviolet light. By using concentrations of cycloheximide or hydroxyurea that inhibit DNA synthesis by a similar amount (70%), but protein synthesis by vastly different amounts (95% for cycloheximide; 0% for hydroxyurea), it was apparent that the delay in recovery caused by the treatment of the cells with cycloheximide could be accounted for entirely by its inhibitory effect on DNA synthesis. This suggests that the recovery in DNA synthetic rates following exposure of V-79 cells to ultraviolet light does not appear to require de novo protein synthesis, and therefore does not appear to require the involvement of an inducible DNA repair process. (Auth.)

Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

Science.gov (United States)

Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

2018-06-01

Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

Thromboxane synthesis inhibitors and postprandial jejunal capillary exchange capacity.

Science.gov (United States)

Mangino, M J; Chou, C C

1988-05-01

The effects of thromboxane synthesis inhibitors (imidazole and U 63557A; Upjohn) and the cyclooxygenase inhibitor, mefenamic acid, on jejunal capillary filtration coefficients (Kfc) were determined in dogs before and during the presence of predigested food in the jejunal lumen. The jejunal Kfc increased significantly soon after the placement of a predigested test food containing all major constituents of diet. The Kfc remained elevated as long as the food was present in the lumen (15 min). Mefenamic acid (10 mg/kg iv) did not significantly alter resting jejunal Kfc or alter the food-induced increase in Kfc. Imidazole (5.0 mg/min ia) or U 63557A (5.0 mg/kg iv) per se significantly increased jejunal Kfc. Placement of digested food further increased the Kfc to levels significantly higher than those observed before administration of the two thromboxane synthase inhibitors. Production of thromboxane B2 by jejunal tissue was significantly reduced and 6-ketoprostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) production was significantly increased after administration of U 63557A. Our study indicates that the relative production of endogenous thromboxanes and other prostanoids modulates jejunal capillary exchange capacity in the absence or presence of digested food in the jejunal lumen.

Synthesis imaging in radio astronomy

International Nuclear Information System (INIS)

Perley, R.A.; Schwab, F.R.; Bridle, A.H.

1989-01-01

Recent advances in techniques and instrumentation for radio synthesis imaging in astronomy are discussed in a collection of review essays. Topics addressed include coherence in radio astronomy, the interferometer in practice, primary antenna elements, cross correlators, calibration and editing, sensitivity, deconvolution, self-calibration, error recognition, and image analysis. Consideration is given to wide-field imaging (bandwidth and time-average smearing, noncoplanar arrays, and mosaicking), high-dynamic-range imaging, spectral-line imaging, VLBI, solar imaging with a synthesis telescope, synthesis imaging of spatially coherent objects, noise in images of very bright sources, synthesis observing strategies, and the design of aperture-synthesis arrays

Feature-aware natural texture synthesis

KAUST Repository

Wu, Fuzhang; Dong, Weiming; Kong, Yan; Mei, Xing; Yan, Dongming; Zhang, Xiaopeng; Paul, Jean Claude

2014-01-01

This article presents a framework for natural texture synthesis and processing. This framework is motivated by the observation that given examples captured in natural scene, texture synthesis addresses a critical problem, namely, that synthesis

Radiation chemical synthesis

International Nuclear Information System (INIS)

Zagoretz, P.A.; Poluetkov, V.A.; Shostenko, A.G.

1986-01-01

The authors consider processes in radiation chemical synthesis which are being developed in various scientific-research organizations. The important advantages of radiation chlorination, viz. the lower temperature compared with the thermal method and the absence of dehydrochlorination products are discussed. The authors examine the liquid-phase chlorination of trifluorochloroethyltrichloromethyl ether to obtain the pentachloro-contining ether, trifluorodichloroethyltrichloromethyl ether. The authors discuss radiation synthesis processes that have be used formulated kinetic equations on which models have been based. It is concluded that the possibilities of preparative (micro- and low-tonnage) radiation synthesis are promising

Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

Science.gov (United States)

Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

2016-04-01

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Click synthesis of PET radiopharmaceuticals

International Nuclear Information System (INIS)

Xu Mei; Kuang Chunxiang

2009-01-01

Increasing attention has been focused on synthesis radiopharmaceuticals for positron emission tomography (PET). The recent years witnessed applications of click chemistry to PET radiopharmaceutical synthesis,because of its distinctive advantages including high speed,yield and stereospecificity under mild conditions. Synthesis of 18 F-labeled and 11 C-labeled radiopharmaceuticals and intermediates via click chemistry are reviewed. The future trend of click chemistry for the synthesis of PET radiopharmaceutical is prospected. (authors)

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

Science.gov (United States)

Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice.

Science.gov (United States)

Reza, Abu Musa Md Talimur; Choi, Yun-Jung; Kim, Jin-Hoi

2018-02-27

The Rag2 knockout (KO) mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic) regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate) are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from Rag2 KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in Rag2 KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory) in Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice

Directory of Open Access Journals (Sweden)

Abu Musa Md Talimur Reza

2018-02-01

Full Text Available The Rag2 knockout (KO mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs and messenger RNAs (mRNAs in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from Rag2 KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in Rag2 KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory in Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

Chemistry, mineralogy and alteration intensity of hydrothermal altered Mt Unzen conduit rocks (Shimabara/Japan)

Science.gov (United States)

Hess, Kai-Uwe; Yilmaz, Tim; Gilg, H. Albert; Janots, Emilie; Mayer, Klaus; Nakada, Setsuya; Dingwell, Donald

2017-04-01

Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, C-O-isotope, hot-cathode CL and SEM analysis led to insights concerning chemistry, mineralogy, and intensity and type of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the volcanic conduit rocks was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite and kaolinite group minerals indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate and chlorite pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite as well as kaolinite group minerals, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite, R1 illite-smectite as well as kaolinite group minerals in the groundmass. Late chlorite veins crosscut precipitates of R1 illite-smectite as well as kaolinite group minerals. Carbonates in fractures and in pseudomorphs after hornblende comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration

Novel Antimicrobial Peptides That Inhibit Gram Positive Bacterial Exotoxin Synthesis

Science.gov (United States)

Merriman, Joseph A.; Nemeth, Kimberly A.; Schlievert, Patrick M.

2014-01-01

Gram-positive bacteria, such as Staphylococcus aureus, cause serious human illnesses through combinations of surface virulence factors and secretion of exotoxins. Our prior studies using the protein synthesis inhibitor clindamycin and signal transduction inhibitors glycerol monolaurate and α-globin and β-globin chains of hemoglobin indicate that their abilities to inhibit exotoxin production by S. aureus are separable from abilities to inhibit growth of the organism. Additionally, our previous studies suggest that inhibition of exotoxin production, in absence of ability to kill S. aureus and normal flora lactobacilli, will prevent colonization by pathogenic S. aureus, while not interfering with lactobacilli colonization. These disparate activities may be important in development of novel anti-infective agents that do not alter normal flora. We initiated studies to explore the exotoxin-synthesis-inhibition activity of hemoglobin peptides further to develop potential agents to prevent S. aureus infections. We tested synthesized α-globin chain peptides, synthetic variants of α-globin chain peptides, and two human defensins for ability to inhibit exotoxin production without significantly inhibiting S. aureus growth. All of these peptides were weakly or not inhibitory to bacterial growth. However, the peptides were inhibitory to exotoxin production with increasing activity dependent on increasing numbers of positively-charged amino acids. Additionally, the peptides could be immobilized on agarose beads or have amino acid sequences scrambled and still retain exotoxin-synthesis-inhibition. The peptides are not toxic to human vaginal epithelial cells and do not inhibit growth of normal flora L. crispatus. These peptides may interfere with plasma membrane signal transduction in S. aureus due to their positive charges. PMID:24748386

Effects of Walker 256 carcinoma on metabolic alterations during the evolution of pregnancy.

Science.gov (United States)

Cintra-Gomes, M C; Cury, L; Parreira, M R; Elias, C F; Areas, M A

1990-01-01

The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pregnant tumor-bearing rats. The tumor-bearing and pregnant tumor-bearing groups showed a decrease in blood glucose and total serum protein, suggesting an increase in energy utilization of these substrates and synthetic activity by the tumoral cells. An imbalance between protein synthesis and catabolism may occur in the tumor-bearing rats which may be related to the degree of nutritional depletion.

Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

Science.gov (United States)

Bonsall, David R; Kokkinou, Michelle; Veronese, Mattia; Coello, Christopher; Wells, Lisa A; Howes, Oliver D

2017-12-01

Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug. © 2017 International Society for Neurochemistry.

Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

Directory of Open Access Journals (Sweden)

Heidi O Nousiainen

Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line

International Nuclear Information System (INIS)

Blusztajn, J.K.; Liscovitch, M.; Richardson, U.I.

1987-01-01

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used a precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here the authors used a population of purely cholinergic cells (human neuroblastomas, LA-N-2), incubated in the presence of [methyl- 3 H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. Three peaks of radioactive material that cochromatographed with authentic AcCho, choline, and phosphocholine were observed when the water-soluble metabolites of the [ 3 H]PtdCho were purified by high-performance liquid chromatography. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine

Early steps in protein synthesis and their regulation: a background study related to the biological effects of radiation. Progress report, July 1, 1974--June 30, 1975

International Nuclear Information System (INIS)

Zamecnik, P.C.

1975-01-01

The proposed program is an interwoven effort to study the details of the mechanism of protein synthesis in normal living systems and their alterations in the presence of oncogenic RNA viruses using the avian myeloblastosis virus as a model. Emphasis will be placed on determining the role of the primary structure of the viral RNA and of other factors required for the production of viral proteins in a cell-free system. Continued studies of the initial steps of protein synthesis where much specificity is determined by the tRNA: tRNA synthetase interactions will be carried out using biochemical and genetic techniques. (U.S.)

Synthesis of Mechanisms

DEFF Research Database (Denmark)

Hansen, John Michael

1999-01-01

These notes describe an automated procedure for analysis and synthesis of mechanisms. The analysis method is based on the body coordinate formulation, and the synthesis is based on applying optimization methods, used to minimize the difference between an actual and a desired behaviour...

Green synthesis of silver nanoparticles aimed at improving theranostics

Science.gov (United States)

Vedelago, José; Gomez, Cesar G.; Valente, Mauro; Mattea, Facundo

2018-05-01

Nowadays, the combination of diagnosis and therapy, known as theranostics, is one of the keys for an optimal treatment for cancer diseases. Theranostics can be significantly improved by incorporating metallic nanoparticles that are specifically delivered and accumulated in cancerous tissue. In this context, precise knowledge about dosimetric effects in nanoparticle-infused tissues as well as the detection and processing of emerging radiation are extremely important issues. In the last years the first studies on theranostic nanomaterials in gel dosimetry have been presented but there is still a broad field of study to explore. Most of gel dosimetric materials are extremely sensible to modifications in their composition, the addition of enhancers, metallic or inorganic charges can alter their stability and dosimetric properties; therefore, thorough studies must be made before the incorporation of any type of modifier. In this work, the synthesis of metallic nanoparticles suitable for gel dosimetry for x-ray applications is presented. A green synthesis process of silver nanoparticles coated with porcine skin gelatin by thermal reduction of silver nitrate is presented. Nanoparticles were obtained and purified for their application in gel dosimetry. Also, nanoparticles size distribution, reaction yield and the preliminar application as theranostic agents were tested in Fricke gel dosimetry in the keV range. The obtained nanoparticles were successfully used in theranostic applications acting as fluorescent agents and dose enhancers in X-ray beam irradiation simultaneously.

Great Lakes rivermouth ecosystems: scientific synthesis and management implications

Science.gov (United States)

Larson, James H.; Trebitz, Anett S.; Steinman, Alan D.; Wiley, Michael J.; Carlson Mazur, Martha; Pebbles, Victoria; Braun, Heather A.; Seelbach, Paul W.

2013-01-01

At the interface of the Great Lakes and their tributary rivers lies the rivermouths, a class of aquatic ecosystem where lake and lotic processes mix and distinct features emerge. Many rivermouths are the focal point of both human interaction with the Great Lakes and human impacts to the lakes; many cities, ports, and beaches are located in rivermouth ecosystems, and these human pressures often degrade key ecological functions that rivermouths provide. Despite their ecological uniqueness and apparent economic importance, there has been relatively little research on these ecosystems as a class relative to studies on upstream rivers or the open-lake waters. Here we present a synthesis of current knowledge about ecosystem structure and function in Great Lakes rivermouths based on studies in both Laurentian rivermouths, coastal wetlands, and marine estuarine systems. A conceptual model is presented that establishes a common semantic framework for discussing the characteristic spatial features of rivermouths. This model then is used to conceptually link ecosystem structure and function to ecological services provided by rivermouths. This synthesis helps identify the critical gaps in understanding rivermouth ecology. Specifically, additional information is needed on how rivermouths collectively influence the Great Lakes ecosystem, how human alterations influence rivermouth functions, and how ecosystem services provided by rivermouths can be managed to benefit the surrounding socioeconomic networks.

Effect of irradiation on unscheduled DNA synthesis induced by 4-nitroquinoline in tracheal epithelium of rats

International Nuclear Information System (INIS)

Hahn, F.F.; Kennedy, R.; Brooks, A.L.

1986-01-01

Unscheduled DNA synthesis (UDS) was determined in rat epithelium by autoradiographic techniques to determine the influence of prior irradiation on the ability of the cells to repair mutagenic damage induced by 4-nitroquionoline (4NQO). UDS was stimulated by in vitro exposure to 4NPO. However, prior whole-body irradiation of rats with either 50 or 300 rad did not alter the UDS induced by 4NQO. The results of this study do not support the hypothesis that irradiation can induce DNA repair enzymes in respiratory tract epithelium. 5 references, 3 figures

Yeast-assisted synthesis of polypyrrole: Quantification and influence on the mechanical properties of the cell wall.

Science.gov (United States)

Andriukonis, Eivydas; Stirke, Arunas; Garbaras, Andrius; Mikoliunaite, Lina; Ramanaviciene, Almira; Remeikis, Vidmantas; Thornton, Barry; Ramanavicius, Arunas

2018-04-01

In this study, the metabolism of yeast cells (Saccharomyces cerevisiae) was utilized for the synthesis of the conducting polymer - polypyrrole (Ppy).Yeast cells were modified in situ by synthesized Ppy. The Ppy was formed in the cell wall by redox-cycling of [Fe(CN) 6 ] 3-/4- , performed by the yeast cells. Fluorescence microscopy, enzymatic digestions, atomic force microscopy and isotope ratio mass spectroscopy were applied to determine both the polymerization reaction itself and the polymer location in yeast cells. Ppy formation resulted in enhanced resistance to lytic enzymes, significant increase of elasticity and alteration of other mechanical cell wall properties evaluated by atomic force microscopy (AFM). The suggested method of polymer synthesis allows the introduction of polypyrrole structures within the cell wall, which is build up from polymers consisting of carbohydrates. This cell wall modification strategy could increase the usefulness of yeast as an alternative energy source in biofuel cells, and in cell based biosensors. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

Directory of Open Access Journals (Sweden)

Ariel B. Ganz

2017-01-01

Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

The effect of NGATHA altered activity in auxin signaling pathways within the Arabidopsis gynoecium

Directory of Open Access Journals (Sweden)

Irene eMartinez-Fernandez

2014-05-01

Full Text Available The four NGATHA genes (NGA form a small subfamily within the large family of B3-domain transcription factors of Arabidopsis thaliana. NGA genes act redundantly to direct the development of the apical tissues of the gynoecium, the style and the stigma. Previous studies indicate that NGA genes could exert this function at least partially by directing the synthesis of auxin at the distal end of the developing gynoecium through the upregulation of two different YUCCA genes, which encode flavin monooxygenases involved in auxin biosynthesis. We have compared three developing pistil transcriptome data sets from wildtype, nga quadruple mutants and a 35S::NGA3 line. The differentially expressed genes showed a significant enrichment for auxin-related genes, supporting the idea of NGA genes as major regulators of auxin accumulation and distribution within the developing gynoecium.We have introduced reporter lines for several of these differentially expressed genes involved in synthesis, transport and response to auxin in NGA gain- and loss-of-function backgrounds. We present here a detailed map of the response of these reporters to NGA misregulation that could help to clarify the role of NGA in auxin-mediated gynoecium morphogenesis. Our data point to a very reduced auxin synthesis in the developing apical gynoecium of nga mutants, likely responsible for the lack of DR5rev::GFP reporter activity observed in these mutants. In addition, NGA altered activity affects the expression of protein kinases that regulate the cellular localization of auxin efflux regulators, and thus likely impact auxin transport. Finally, protein accumulation in pistils of several ARFs was differentially affected by nga mutations or NGA overexpression, suggesting that these accumulation patterns depend not only on auxin distribution but could be also regulated by transcriptional networks involving NGA factors.

Influence of nutrition on protein synthesis and 15N tracer data in man

International Nuclear Information System (INIS)

Faust, H.

1984-01-01

Quantitative studies and measurements of parameters of the protein metabolism in vivo require the isotope methodology. Different 15 N tracer methods with special modifications are available which can be used depending on clinical problems. The oral single pulse application of [ 15 N]glycine is equal to other isotope tracer techniques provided that the basic assumptions of the application are fullfilled. The protein metabolism is clearly influenced by the nutritional status whereby the protein synthesis is more sensitive than the breakdown to altered dietary intakes of protein and energy. The importance of standardized experimental conditions is emphasized for studies with 15 N and the interpretation of tracer data. (author)

VHDL for logic synthesis

CERN Document Server

Rushton, Andrew

2011-01-01

Many engineers encountering VHDL (very high speed integrated circuits hardware description language) for the first time can feel overwhelmed by it. This book bridges the gap between the VHDL language and the hardware that results from logic synthesis with clear organisation, progressing from the basics of combinational logic, types, and operators; through special structures such as tristate buses, register banks and memories, to advanced themes such as developing your own packages, writing test benches and using the full range of synthesis types. This third edition has been substantially rewritten to include the new VHDL-2008 features that enable synthesis of fixed-point and floating-point hardware. Extensively updated throughout to reflect modern logic synthesis usage, it also contains a complete case study to demonstrate the updated features. Features to this edition include: * a common VHDL subset which will work across a range of different synthesis systems, targeting a very wide range of technologies...

Exploring and Implementing Participatory Action Synthesis

Science.gov (United States)

Wimpenny, Katherine; Savin-Baden, Maggi

2012-01-01

This article presents participatory action synthesis as a new approach to qualitative synthesis which may be used to facilitate the promotion and use of qualitative research for policy and practice. The authors begin by outlining different forms of qualitative research synthesis and then present participatory action synthesis, a collaborative…

Six1 induces protein synthesis signaling expression in duck myoblasts mainly via up-regulation of mTOR

Directory of Open Access Journals (Sweden)

Haohan Wang

2016-03-01

Full Text Available Abstract As a critical transcription factor, Six1 plays an important role in the regulation of myogenesis and muscle development. However, little is known about its regulatory mechanism associated with muscular protein synthesis. The objective of this study was to investigate the effects of overexpression ofSix1 on the expression of key protein metabolism-related genes in duck myoblasts. Through an experimental model where duck myoblasts were transfected with a pEGFP-duSix1 construct, we found that overexpression of duckSix1 could enhance cell proliferation activity and increase mRNA expression levels of key genes involved in the PI3K/Akt/mTOR signaling pathway, while the expression of FOXO1, MuRF1and MAFbx was not significantly altered, indicating thatSix1 could promote protein synthesis in myoblasts through up-regulating the expression of several related genes. Additionally, in duck myoblasts treated with LY294002 and rapamycin, the specific inhibitors ofPI3K and mTOR, respectively, the overexpression of Six1 could significantly ameliorate inhibitive effects of these inhibitors on protein synthesis. Especially, the mRNA expression levels of mTOR and S6K1 were observed to undergo a visible change, and a significant increase in protein expression of S6K1 was seen. These data suggested that Six1plays an important role in protein synthesis, which may be mainly due to activation of the mTOR signaling pathway.

Synthesis of polyaryl rigid-core carbosilane dendrimers for supported organic synthesis

NARCIS (Netherlands)

Wander, M.; Hausoul, P.J.C.; Sliedregt, L.A.J.M.; van Steen, B.J.; van Koten, G.; Klein Gebbink, R.J.M.

2009-01-01

Carbosilane dendrimers can be used as soluble supports for organic synthesis, since their structure allows separation of excess reagents from the supported products, eventually yielding products of high purity and in high yield, as in solid-phase organic synthesis (SPOS). In previous studies often

Transpeptidase activity of penicillin-binding protein SpoVD in peptidoglycan synthesis conditionally depends on the disulfide reductase StoA.

Science.gov (United States)

Bukowska-Faniband, Ewa; Hederstedt, Lars

2017-07-01

Endospore cortex peptidoglycan synthesis is not required for bacterial growth but essential for endospore heat resistance. It therefore constitutes an amenable system for research on peptidoglycan biogenesis. The Bacillus subtilis sporulation-specific class B penicillin-binding protein (PBP) SpoVD and many homologous PBPs contain two conserved cysteine residues of unknown function in the transpeptidase domain - one as residue x in the SxN catalytic site motif and the other in a flexible loop near the catalytic site. A disulfide bond between these residues blocks the function of SpoVD in cortex synthesis. With a combination of experiments with purified proteins and B. subtilis mutant cells, it was shown that in active SpoVD the two cysteine residues most probably interact by hydrogen bonding and that this is important for peptidoglycan synthesis in vivo. It was furthermore demonstrated that the sporulation-specific thiol-disulfide oxidoreductase StoA reduces SpoVD and that requirement of StoA for cortex synthesis can be suppressed by two completely different types of structural alterations in SpoVD. It is concluded that StoA plays a critical role mainly during maturation of SpoVD in the forespore outer membrane. The findings advance our understanding of essential PBPs and redox control of extra-cytoplasmic protein disulfides in bacterial cells. © 2017 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

Behavioral synthesis of asynchronous circuits

DEFF Research Database (Denmark)

Nielsen, Sune Fallgaard

2005-01-01

This thesis presents a method for behavioral synthesis of asynchronous circuits, which aims at providing a synthesis flow which uses and tranfers methods from synchronous circuits to asynchronous circuits. We move the synchronous behavioral synthesis abstraction into the asynchronous handshake...... is idle. This reduces unnecessary switching activity in the individual functional units and therefore the energy consumption of the entire circuit. A collection of behavioral synthesis algorithms have been developed allowing the designer to perform time and power constrained design space exploration...

Regulation of chloroplast number and DNA synthesis in higher plants. Final report

Energy Technology Data Exchange (ETDEWEB)

Mullet, J.E.

1995-11-10

The long term objective of this research is to understand the process of chloroplast development and its coordination with leaf development in higher plants. This is important because the photosynthetic capacity of plants is directly related to leaf and chloroplast development. This research focuses on obtaining a detailed description of leaf development and the early steps in chloroplast development including activation of plastid DNA synthesis, changes in plastid DNA copy number, activation of chloroplast transcription and increases in plastid number per cell. The grant will also begin analysis of specific biochemical mechanisms by isolation of the plastid DNA polymerase, and identification of genetic mutants which are altered in their accumulation of plastid DNA and plastid number per cell.

An improved synthesis process of calixcrown ethers and synthesis of novel calixcrown ether

International Nuclear Information System (INIS)

Wang Hairong; Zhang Ping; Wang Chunmiao; Wang Jianchen; Chen Jing

2007-01-01

The synthesis method of calixcrown ethers was simplified and improved, and 10 L- scale synthesis was carried out. In the synthesis of the intermediates of the first three steps, the synthesis of 5, 11, 17, 23-tetra-tert-butyl-25, 26, 27, 28-tetrahydroxyl-calix[4] and its dehydroxylation were considered together, the purification procedures of the former, including re-crystallization in toluene and decolorization with activated carbon, were cancelled, and thus these steps were simplified. In the synthesis of oligoethylene glycol ditosylate, the purification method was also improved and the time-consuming column chromatography was left out. In the final step, impurities were removed by repeating stirring-settlement steps, by following recrystallization, the pure product was obtained. With these measures, the whole process could be implemented easily. The industrial scale production of calixcrown ethers could be fulfilled with the improved process. In addition, a new extracant, 25, 27-bis (n-propyloxy)calix[4]-26, 28-crown-6, is prepared and identified. (authors)

What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis.

Science.gov (United States)

Schick-Makaroff, Kara; MacDonald, Marjorie; Plummer, Marilyn; Burgess, Judy; Neander, Wendy

2016-01-01

When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use 'research synthesis' as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers.

Human MiR-544a Modulates SELK Expression in Hepatocarcinoma Cell Lines.

Directory of Open Access Journals (Sweden)

Nicoletta Potenza

Full Text Available Hepatocellular carcinoma (HCC is a multi-factorial cancer with a very poor prognosis; therefore, there are several investigations aimed at the comprehension of the molecular mechanisms leading to development and progression of HCC and at the definition of new therapeutic strategies. We have recently evaluated the expression of selenoproteins in HCC cell lines in comparison with normal hepatocytes. Recent results have shown that some of them are down- and others up-regulated, including the selenoprotein K (SELK, whose expression was also induced by sodium selenite treatment on cells. However, so far very few studies have been dedicated to a possible effect of microRNAs on the expression of selenoproteins and their implication in HCC. In this study, the analysis of SELK 3'UTR by bioinformatics tools led to the identification of eight sites potentially targeted by human microRNAs. They were then subjected to a validation test based on luciferase reporter constructs transfected in HCC cell lines. In this functional screening, miR-544a was able to interact with SELK 3'UTR suppressing the reporter activity. Transfection of a miR-544a mimic or inhibitor was then shown to decrease or increase, respectively, the translation of the endogenous SELK mRNA. Intriguingly, miR-544a expression was found to be modulated by selenium treatment, suggesting a possible role in SELK induction by selenium.

Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants

Science.gov (United States)

Guan, Zhuo; Buhl, Lauren K.; Quinn, William G.; Littleton, J. Troy

2011-01-01

Genetic studies in Drosophila have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in radish (rsh) mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways leading to these forms of memory may share the cAMP cascade critical for associative learning. Dunce, which encodes a cAMP-specific phosphodiesterase, and rutabaga, which encodes an adenylyl cyclase, both disrupt short-term memory. Amnesiac encodes a pituitary adenylyl cyclase-activating peptide homolog and is required for middle-term memory. Here, we demonstrate that the Radish protein localizes to the cytoplasm and nucleus and is a PKA phosphorylation target in vitro. To characterize how these plasticity pathways may manifest at the synaptic level, we assayed synaptic connectivity and performed an expression analysis to detect altered transcriptional networks in rutabaga, dunce, amnesiac, and radish mutants. All four mutants disrupt specific aspects of synaptic connectivity at larval neuromuscular junctions (NMJs). Genome-wide DNA microarray analysis revealed ∼375 transcripts that are altered in these mutants, suggesting defects in multiple neuronal signaling pathways. In particular, the transcriptional target Lapsyn, which encodes a leucine-rich repeat cell adhesion protein, localizes to synapses and regulates synaptic growth. This analysis provides insights into the Radish-dependent ARM pathway and novel transcriptional targets that may contribute to memory processing in Drosophila. PMID:21422168

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

Science.gov (United States)

2016-01-01

The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis. PMID:27120289

Altered selenium status in Huntington's disease: neuroprotection by selenite in the N171-82Q mouse model.

Science.gov (United States)

Lu, Zhen; Marks, Eileen; Chen, Jianfang; Moline, Jenna; Barrows, Lorraine; Raisbeck, Merl; Volitakis, Irene; Cherny, Robert A; Chopra, Vanita; Bush, Ashley I; Hersch, Steven; Fox, Jonathan H

2014-11-01

Disruption of redox homeostasis is a prominent feature in the pathogenesis of Huntington's disease (HD). Selenium an essential element nutrient that modulates redox pathways and has been reported to provide protection against both acute neurotoxicity (e.g. methamphetamine) and chronic neurodegeneration (e.g. tauopathy) in mice. The objective of our study was to investigate the effect of sodium selenite, an inorganic form of selenium, on behavioral, brain degeneration and biochemical outcomes in the N171-82Q Huntington's disease mouse model. HD mice, which were supplemented with sodium selenite from 6 to 14 weeks of age, demonstrated increased motor endurance, decreased loss of brain weight, decreased mutant huntingtin aggregate burden and decreased brain oxidized glutathione levels. Biochemical studies revealed that selenite treatment reverted HD-associated changes in liver selenium and plasma glutathione in N171-82Q mice and had effects on brain selenoprotein transcript expression. Further, we found decreased brain selenium content in human autopsy brain. Taken together, we demonstrate a decreased selenium phenotype in human and mouse HD and additionally show some protective effects of selenite in N171-82Q HD mice. Modification of selenium metabolism results in beneficial effects in mouse HD and thus may represent a therapeutic strategy. Copyright © 2014 Elsevier Inc. All rights reserved.

Cesium Carbonate as a Heterogeneous Base Catalyst for Synthesis of 2-Aminothiophenes via Gewald Reaction

Energy Technology Data Exchange (ETDEWEB)

Moeinpour, Farid [Islamic Azad University, Bandar Abbas Branch, Abbas (Iran, Islamic Republic of); Omidinia, Raheleh; Dorostkar-Ahmadi, Nadieh; Khoshdeli, Bentalhoda [Islamic Azad University, Mashhad Branch, Mashhad (Iran, Islamic Republic of)

2011-06-15

We have reported a new simple catalytic method for the synthesis of 2-aminothiophenes via Gewald reaction using Cs{sub 2}CO{sub 3} as an efficient, reusable and green heterogeneous catalyst under heating conditions in refluxing ethanol. The catalyst could be recycled after a simple workup and reused at least three runs without appreciable reduction in its catalytic activity. Low catalyst loading, clean reaction profiles, simple experimental and workup procedures and high yields are some advantages of this protocol. The synthesis of substituted 2-aminothiophenes is attractive to chemical researchers as they are important intermediates in organic synthesis and frequently used as the scaffold motif of a variety of agrochemicals, dyes, and biologically active products. Thus, because of their wide utility, researchers have synthesized the substituted 2-aminothiophenes via efficient and convenient methods. The one-pot cyclocondensation of ketones with an activated α-hydrogen, a cyanomethylene containing an electron-withdrawing group such as cyanoacetate and elemental sulfur in the presence of organic base, for example, morpholine, diethylamine, etc, known as the Gewald reaction, has been one of the most well-studied multicomponent reactions in recent years. To extend the scope of the reaction, many alterations have been made to the original Gewald's base-catalyzed, two-component combination of α-mercapto ketones with cyanoacetate by varying the components and the conditions.

Synthesis centers as critical research infrastructure

Science.gov (United States)

Baron, Jill S.; Specht, Alison; Garnier, Eric; Bishop, Pamela; Campbell, C. Andrew; Davis, Frank W.; Fady, Bruno; Field, Dawn; Gross, Louis J.; Guru, Siddeswara M.; Halpern, Benjamin S; Hampton, Stephanie E.; Leavitt, Peter R.; Meagher, Thomas R.; Ometto, Jean; Parker, John N.; Price, Richard; Rawson, Casey H.; Rodrigo, Allen; Sheble, Laura A.; Winter, Marten

2017-01-01

Demand for the opportunity to participate in a synthesis-center activity has increased in the years since the US National Science Foundation (NSF)–funded National Center for Ecological Analysis and Synthesis (NCEAS) opened its doors in 1995 and as more scientists across a diversity of scientific disciplines have become aware of what synthesis centers provide. The NSF has funded four synthesis centers, and more than a dozen new synthesis centers have been established around the world, some following the NSF model and others following different models suited to their national funding environment (http://synthesis-consortium.org).Scientific synthesis integrates diverse data and knowledge to increase the scope and applicability of results and yield novel insights or explanations within and across disciplines (Pickett et al. 2007, Carpenter et al. 2009). The demand for synthesis comes from the pressing societal need to address grand challenges related to global change and other issues that cut across multiple societal sectors and disciplines and from recognition that substantial added scientific value can be achieved through the synthesis-based analysis of existing data. Demand also comes from groups of scientists who see exciting opportunities to generate new knowledge from interdisciplinary and transdisciplinary collaboration, often capitalizing on the increasingly large volume and variety of available data (Kelling et al. 2009, Bishop et al. 2014, Specht et al. 2015b). The ever-changing nature of societal challenges and the availability of data with which to address them suggest there will be an expanding need for synthesis.However, we are now entering a phase in which government support for some existing synthesis centers has ended or will be ending soon, forcing those centers to close or develop new operational models, approaches, and funding streams. We argue here that synthesis centers play such a unique role in science that continued long-term public

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

Energy Technology Data Exchange (ETDEWEB)

Hotchkiss, J A; Portereiko, J V; Harkema, J R

1988-12-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

International Nuclear Information System (INIS)

Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

1988-01-01

Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

A novel solution combustion synthesis of cobalt oxide nanoparticles as negative-electrode materials for lithium ion batteries

International Nuclear Information System (INIS)

Wen Wei; Wu Jinming; Tu Jiangping

2012-01-01

Highlights: ► We examine the electrochemical performance of cobalt oxides fabricated by solution combustion synthesis for rechargeable lithium-ion battery applications. ► The additive of NaF in precursor results in an eruption combustion mode. ► The eruption combustion leads to fluffy networks with smaller grains and more macroporous voids. ► The network contributes to higher discharge capacity, higher initial coulombic efficiency, and better cycling performance for rechargeable lithium-ion batteries. - Abstract: Low cost mass production of cobalt oxide nanoparticles with high electrochemical performance is of practical interest for rechargeable lithium-ion batteries. In this report, cobalt oxide nanoparticles were fabricated by solution combustion synthesis, with the introduction of NaF into the precursor to alter the combustion mode. The novel eruption combustion resulted in fluffy networks with smaller particles and more macroporous voids, which contributed to the higher discharge capacity, higher initial coulombic efficiency, and better cycling performance when compared with that achieved by the conventional combustion mode.

RNS60, a charge-stabilized nanostructure saline alters Xenopus Laevis oocyte biophysical membrane properties by enhancing mitochondrial ATP production

Science.gov (United States)

Choi, Soonwook; Yu, Eunah; Kim, Duk-Soo; Sugimori, Mutsuyuki; Llinás, Rodolfo R

2015-01-01

We have examined the effects of RNS60, a 0.9% saline containing charge-stabilized oxygen nanobubble-based structures. RNS60 is generated by subjecting normal saline to Taylor–Couette–Poiseuille (TCP) flow under elevated oxygen pressure. This study, implemented in Xenopus laevis oocytes, addresses both the electrophysiological membrane properties and parallel biological processes in the cytoplasm. Intracellular recordings from defolliculated X. laevis oocytes were implemented in: (1) air oxygenated standard Ringer's solution, (2) RNS60-based Ringer's solution, (3) RNS10.3 (TCP-modified saline without excess oxygen)-based Ringer's, and (4) ONS60 (saline containing high pressure oxygen without TCP modification)-based Ringer's. RNS60-based Ringer's solution induced membrane hyperpolarization from the resting membrane potential. This effect was prevented by: (1) ouabain (a blocker of the sodium/potassium ATPase), (2) rotenone (a mitochondrial electron transfer chain inhibitor preventing usable ATP synthesis), and (3) oligomycin A (an inhibitor of ATP synthase) indicating that RNS60 effects intracellular ATP levels. Increased intracellular ATP levels following RNS60 treatment were directly demonstrated using luciferin/luciferase photon emission. These results indicate that RNS60 alters intrinsic the electrophysiological properties of the X. laevis oocyte membrane by increasing mitochondrial-based ATP synthesis. Ultrastructural analysis of the oocyte cytoplasm demonstrated increased mitochondrial length in the presence of RNS60-based Ringer's solution. It is concluded that the biological properties of RNS60 relate to its ability to optimize ATP synthesis. PMID:25742953

Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

Science.gov (United States)

Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

2017-11-01

The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

Chlorite alteration in aqueous solutions and uranium removal by altered chlorite

Energy Technology Data Exchange (ETDEWEB)

Kim, Eungyeong; Ahn, Hyangsig [Department of Earth and Environmental Sciences, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841 (Korea, Republic of); Jo, Ho Young, E-mail: hyjo@korea.ac.kr [Department of Earth and Environmental Sciences, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841 (Korea, Republic of); Ryu, Ji-Hun; Koh, Yong-Kwon [Korea Atomic Energy Research Institute, 1045 Daedeokdaero, Yuseong-gu, Daejeon 34057 (Korea, Republic of)

2017-04-05

Highlights: • Chlorite alteration and the U removal capacity of altered chlorite were investigated. • Initial pH affected more chlorite dissolution than ionic strength. • Chlorite dissolution at pH{sub o} = 3–8 was inversely proportional to the U removal capacity. • Chlorite dissolution at pH{sub o} = 10 was proportional to the U removal capacity. • The formation of Fe-containing secondary minerals affected the U removal capacity. - Abstract: Chlorite alteration and the U removal capacity of altered chlorite were investigated. Batch kinetic dissolution tests using clinochlore CCa-2 were conducted for 60 days in aqueous solutions of various pHs and ionic strengths. Batch sorption tests using these altered chlorite samples were conducted for 48 h with natural groundwater containing 3.06 × 10{sup −6} M U. Chlorite dissolution was influenced more by pH{sub o} than by the ionic strength of the solution. TEM analysis revealed Fe(oxy)hydroxide aggregates in the solid residue from the batch dissolution test with 0.1 M NaClO{sub 4} solution at pH{sub o} = 10. The U removal capacity of the reacted chlorite samples at pH{sub o} = 6–10 was higher than that of the reacted chlorite samples at pH{sub o} = 3. The degree of dissolution of chlorite samples reacted at pH{sub o} = 3–8 was inversely proportional to the U removal capacity, but that of chlorite samples reacted at pH{sub o} = 10 was proportional to the U removal capacity. The positive correlation between the U removal capacity and degree of chlorite dissolution at pH{sub o} = 10 might be due to the formation of Fe-containing secondary minerals and changes in the reactive sites.

Gas Phase Nanoparticle Synthesis

Science.gov (United States)

Granqvist, Claes; Kish, Laszlo; Marlow, William

This book deals with gas-phase nanoparticle synthesis and is intended for researchers and research students in nanomaterials science and engineering, condensed matter physics and chemistry, and aerosol science. Gas-phase nanoparticle synthesis is instrumental to nanotechnology - a field in current focus that raises hopes for environmentally benign, resource-lean manufacturing. Nanoparticles can be produced by many physical, chemical, and even biological routes. Gas-phase synthesis is particularly interesting since one can achieve accurate manufacturing control and hence industrial viability.

BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase.

Science.gov (United States)

Moreau, Karen; Dizin, Eva; Ray, Hind; Luquain, Céline; Lefai, Etienne; Foufelle, Fabienne; Billaud, Marc; Lenoir, Gilbert M; Venezia, Nicole Dalla

2006-02-10

Germ line alterations in BRCA1 (breast cancer susceptibility gene 1) are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 acts as a scaffold protein implicated in multiple cellular functions, such as transcription, DNA repair, and ubiquitination. However, the molecular mechanisms responsible for tumorigenesis are not yet fully understood. We have recently demonstrated that BRCA1 interacts in vivo with acetyl coenzyme A carboxylase alpha (ACCA) through its tandem of BRCA1 C terminus (BRCT) domains. To understand the biological function of the BRCA1.ACCA complex, we sought to determine whether BRCA1 is a regulator of lipogenesis through its interaction with ACCA. We showed here that RNA inhibition-mediated down-regulation of BRCA1 expression induced a marked increase in the fatty acid synthesis. We then delineated the biochemical characteristics of the complex and found that BRCA1 interacts solely with the phosphorylated and inactive form of ACCA (P-ACCA). Finally, we demonstrated that BRCA1 affects lipid synthesis by preventing P-ACCA dephosphorylation. These results suggest that BRCA1 affects lipogenesis through binding to P-ACCA, providing a new mechanism by which BRCA1 may exert a tumor suppressor function.

Cutaneous effects of topical indomethacin, an inhibitor of prostaglandin synthesis, on uv-damaged skin

International Nuclear Information System (INIS)

Snyder, D.S.

1975-01-01

Topical application of a 2.5 percent indomethacin (IM) solution to the sunburned skin of humans and guinea pigs resulted in a marked decrease in ultraviolet light (UVL)-induced erythema. In humans, a decrease in skin temperature and hyperalgesia to near normal levels was also observed. Epidermal responses to UVL injury such as keratinocyte cell death and altered DNA synthesis proceeded unmodified by IM. Repeated applications of IM in the 48-hr period following UVL exposure did not improve upon the results obtained following a single treatment. Guinea-pig skin provides a relevant model system for evaluating the effects of topical nonsteroidal anti-inflammatory agents on sunburn

Oleic acid blocks EGF-induced [Ca2+]i release without altering cellular metabolism in fibroblast EGFR T17.

Science.gov (United States)

Zugaza, J L; Casabiell, X A; Bokser, L; Casanueva, F F

1995-02-06

EGFR-T17 cells were pretreated with oleic acid and 5-10 minutes later stimulated with EGF, to study if early ionic signals are instrumental in inducing metabolic cellular response. Oleic acid blocks EGF-induced [Ca2+]i rise and Ca2+ influx without altering 2-deoxyglucose and 2-aminobutiryc acid uptake nor acute, nor chronically. Oleic acid it is shown, in the first minutes favors the entrance of both molecules to modify the physico-chemical membrane state. On the other hand, oleic acid is unable to block protein synthesis. The results suggest that EGF-induced Ins(1,4,5)P3/Ca2+ pathway does not seem to be decisive in the control of cellular metabolic activity.

Altered Sensory Feedbacks in Pianist's Dystonia: the altered auditory feedback paradigm and the glove effect

Directory of Open Access Journals (Sweden)

Felicia Pei-Hsin Cheng

2013-12-01

Full Text Available Background: This study investigates the effect of altered auditory feedback (AAF in musician's dystonia (MD and discusses whether altered auditory feedback can be considered as a sensory trick in MD. Furthermore, the effect of AAF is compared with altered tactile feedback, which can serve as a sensory trick in several other forms of focal dystonia. Methods: The method is based on scale analysis (Jabusch et al. 2004. Experiment 1 employs synchronization paradigm: 12 MD patients and 25 healthy pianists had to repeatedly play C-major scales in synchrony with a metronome on a MIDI-piano with 3 auditory feedback conditions: 1. normal feedback; 2. no feedback; 3. constant delayed feedback. Experiment 2 employs synchronization-continuation paradigm: 12 MD patients and 12 healthy pianists had to repeatedly play C-major scales in two phases: first in synchrony with a metronome, secondly continue the established tempo without the metronome. There are 4 experimental conditions, among them 3 are the same altered auditory feedback as in Experiment 1 and 1 is related to altered tactile sensory input. The coefficient of variation of inter-onset intervals of the key depressions was calculated to evaluate fine motor control. Results: In both experiments, the healthy controls and the patients behaved very similarly. There is no difference in the regularity of playing between the two groups under any condition, and neither did AAF nor did altered tactile feedback have a beneficial effect on patients’ fine motor control. Conclusions: The results of the two experiments suggest that in the context of our experimental designs, AAF and altered tactile feedback play a minor role in motor coordination in patients with musicians' dystonia. We propose that altered auditory and tactile feedback do not serve as effective sensory tricks and may not temporarily reduce the symptoms of patients suffering from MD in this experimental context.

Genetics Home Reference: multiminicore disease

Science.gov (United States)

... are less common than the classic form, together accounting for about 25 percent of all cases. The ... making a protein called selenoprotein N. Although its function is unknown, researchers suspect that this protein may ...

Effect of Traditional Processing Techniques on the Nutritional and ...

African Journals Online (AJOL)

Michael Horsfall

Composition of African Bread-Fruit (Treculia africana) Seeds. *IFEOMA I IJEH .... located mainly in the seed coat (Kumar et al, 1979;. Singh ... development and control of some metabolic processes ... (1996). Regulation of selenoprotein gene.

Synthesis of Isoiminosugars

DEFF Research Database (Denmark)

Hyldtoft, Lene; Godskesen, Michael Anders; Lundt, Inge

1998-01-01

A short synthesis of isoiminosugars have been developed. Bromolactones are diastereoselectively alkylated at C-2 followed by ring closure to the corresponding lactams. Reduction of these then gives isoiminosugars......A short synthesis of isoiminosugars have been developed. Bromolactones are diastereoselectively alkylated at C-2 followed by ring closure to the corresponding lactams. Reduction of these then gives isoiminosugars...

Synthesis of derivatives of tetronic acid and pulvinic acid. Total synthesis of norbadione A

International Nuclear Information System (INIS)

Mallinger, A.

2008-11-01

When vegetables like mushrooms are contaminated by radioactive caesium 137, this radioactive caesium is associated to norbadione A, a natural pigment present in two mushroom species and which can be used as a caesium decorporation agent or maybe as protection agent against ionizing radiations. Within this perspective, this research report describes the biosynthesis and the structure and properties of the norbadione A and of pulvinic acids (physicochemical properties, anti-oxidizing properties). Then, it presents the various tetronic acids (3-acyl-, 3-alkyl-, 3-alkoxy-, 3-aryl-tetronic acids and non 3-substituted tetronic acids), their synthesis path as they are described in the literature, and presents a new synthesis approach using a tandem reaction (with different esters or hydroxy esters) and the synthesis of tetronic acids. The author also proposes a new synthesis way for methyl pulvinates, and finally reports the work on the development of a total synthesis of the norbadione A

The solution combustion synthesis of nanophosphors

Energy Technology Data Exchange (ETDEWEB)

Tornga, Stephanie C [Los Alamos National Laboratory

2009-01-01

Nanophosphors are defined as nano-sized (1-100mn), insulating, inorganic materials that emit light under particle or electromagnetic excitation. Their unique luminescence properties provide an excellent potential for applications in radiation detection and imaging. Herein, solution combustion synthesis (SCS) is presented as a method to prepare nanophosphor powders, while X-ray diffraction (XRD), transmission electron microscopy (TEM), photoluminescence (PL), photoluminescence excitation (PLE), and other techniques were used to characterize their structural and optical properties. The goal of this work is to synthesize bright, high-quality powders of nanophosphors, consolidate them into bulk materials and study their structural and optical properties using XRD, TEM, PL, and PLE. SCS is of interest because it is a robust, inexpensive, and facile technique, which yields a significant amount of a wide variety of oxide materials, in a short amount of time. Several practical nanophosphors were synthesized and investigated in this work, including simple oxides such as Y{sub 2}O{sub 3}:Bi, Y{sub 2}O{sub 3}:Tb, Y{sub 2}O{sub 3}:Eu and Gd{sub 2}O{sub 3}:Eu, complex oxides such as Gd{sub 2}SiO{sub 5}:Ce, Y{sub 2}SiO{sub 5}:Ce, Lu{sub 2}SiO{sub 5}:Ce, Zn{sub 2}SiO{sub 4}:Mn, and Y{sub 3}Al{sub 5}O{sub 12}:Ce. Results demonstrate that altering the processing parameters such as water content of the precursor solution, ignition temperature, fuel type and amount, and post-synthesis annealing can significantly improve light output, and that it is possible to optimize the luminescence output of oxyorthosilicates by reducing the amount of silica in the precursor mixture.

Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity.

Science.gov (United States)

Spiller, Henry A

2018-05-01

There is increasing evidence that the pathophysiological target of mercury is in fact selenium, rather than the covalent binding of mercury to sulfur in the body's ubiquitous sulfhydryl groups. The role of selenium in mercury poisoning is multifaceted, bidirectional, and central to understanding the target organ toxicity of mercury. An initial search was performed using Medline/PubMed, Toxline, Google Scholar, and Google for published work on mercury and selenium. These searches yielded 2018 citations. Publications that did not evaluate selenium status or evaluated environmental status (e.g., lake or ocean sediment) were excluded, leaving approximately 500 citations. This initial selection was scrutinized carefully and 117 of the most relevant and representative references were selected for use in this review. Binding of mercury to thiol/sulfhydryl groups: Mercury has a lower affinity for thiol groups and higher affinity for selenium containing groups by several orders of magnitude, allowing for binding in a multifaceted way. The established binding of mercury to thiol moieties appears to primarily involve the transport across membranes, tissue distribution, and enhanced excretion, but does not explain the oxidative stress, calcium dyshomeostasis, or specific organ injury seen with mercury. Effects of mercury on selenium and the role this plays in the pathophysiology of mercury toxicity: Mercury impairs control of intracellular redox homeostasis with subsequent increased intracellular oxidative stress. Recent work has provided convincing evidence that the primary cellular targets are the selenoproteins of the thioredoxin system (thioredoxin reductase 1 and thioredoxin reductase 2) and the glutathione-glutaredoxin system (glutathione peroxidase). Mercury binds to the selenium site on these proteins and permanently inhibits their function, disrupting the intracellular redox environment. A number of other important possible target selenoproteins have been identified

Effect of chlorpromazine on lipid metabolism in aortas from cholesterol-fed rabbits and normal rats, in vitro: inhibition of sterol esterification and modification of phospholipid synthesis

International Nuclear Information System (INIS)

Bell, F.P.

1983-01-01

Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) in isolated arterial microsomes and in intact arterial tissue from the rat and cholesterol-fed rabbit in vitro. In isolated rabbit arterial microsomes, CPZ resulted in a concentration-dependent inhibition of ACAT with 50% inhibition of [1-14C]oleoylCoA incorporation into [14C]cholesteryl esters occurring at 0.1 mM CPZ. CPZ also effectively inhibited the incorporation of [14C]oleate into triglycerides without affecting incorporation into diglycerides. Additionally, CPZ altered the pattern of arterial phospholipids synthesized from [1-14C]oleate. Incorporation into phosphatidylcholine was depressed while incorporation into phosphatidylinositol was increased. Since diglyceride synthesis appeared to be unaffected by CPZ, a redirection of phosphatidic acid into the CDP-diglyceride pathway of glycerolipid synthesis does not adequately account for the effect of CPZ on arterial phospholipid and triglyceride synthesis in these experiments

Total synthesis of ciguatoxin.

Science.gov (United States)

Hamajima, Akinari; Isobe, Minoru

2009-01-01

Something fishy: Ciguatoxin (see structure) is one of the principal toxins involved in ciguatera poisoning and the target of a total synthesis involving the coupling of three segments. The key transformations in this synthesis feature acetylene-dicobalthexacarbonyl complexation.

Measurement of Heme Synthesis Levels in Mammalian Cells.

Science.gov (United States)

Hooda, Jagmohan; Alam, Maksudul; Zhang, Li

2015-07-09

Heme serves as the prosthetic group for a wide variety of proteins known as hemoproteins, such as hemoglobin, myoglobin and cytochromes. It is involved in various molecular and cellular processes such as gene transcription, translation, cell differentiation and cell proliferation. The biosynthesis levels of heme vary across different tissues and cell types and is altered in diseased conditions such as anemia, neuropathy and cancer. This technique uses [4-(14)C] 5-aminolevulinic acid ([(14)C] 5-ALA), one of the early precursors in the heme biosynthesis pathway to measure the levels of heme synthesis in mammalian cells. This assay involves incubation of cells with [(14)C] 5-ALA followed by extraction of heme and measurement of the radioactivity incorporated into heme. This procedure is accurate and quick. This method measures the relative levels of heme biosynthesis rather than the total heme content. To demonstrate the use of this technique the levels of heme biosynthesis were measured in several mammalian cell lines.

Exergy analysis of industrial ammonia synthesis

International Nuclear Information System (INIS)

Kirova-Yordanova, Zornitza

2004-01-01

Exergy consumption of ammonia production plants depends strongly on the ammonia synthesis loop design. Due to the thermodynamically limited low degree of conversion of hydrogen-nitrogen mixture to ammonia, industrial ammonia synthesis is implemented as recycle process (so-called 'ammonia synthesis loop'). Significant quantities of reactants are recycled back to reactor, after the removal of ammonia at low temperatures. Modern ammonia synthesis plants use well-developed heat- and cold recovery to improve the reaction heat utilisation and to reduce the refrigeration costs. In this work, the exergy method is applied to estimate the effect of the most important process parameters on the exergy efficiency of industrial ammonia synthesis. A specific approach, including suitable definitions of the system boundaries and process parameters, is proposed. Exergy efficiency indexes are discussed in order to make the results applicable to ammonia synthesis loops of various designs. The dependence of the exergy losses on properly selected independent process parameters is studied. Some results from detailed exergy analysis of the most commonly used ammonia synthesis loop design configurations at a wide range of selected parameters values are shown

Synthesis through Trans-disciplinarity

DEFF Research Database (Denmark)

Hansen, Hanne Tine Ring

2006-01-01

synthesis is a requirement for creating successful ‘environmentally sustainable' architecture through the application of trans-disciplinarity, which leads to an increased awareness of the differences in decision-making as well as that of communication barriers between the different professions......When looking up the word ‘synthesis' in a dictionary, one comes across the following definition: "The combining of separate elements or substances to form a coherent whole."[1] Based on this definition one could argue that all great architectureis achieved through synthesis in one way or another...

Recovery of subchromosomal DNA synthesis in synchronous V-79 Chinese hamster cells after ultraviolet light exposure

International Nuclear Information System (INIS)

Meechan, P.J.; Carpenter, J.G.

1986-01-01

Previous work obtained from Chinese hamster V-79 cells indicated that, immediately following exposure, UV-induced lesions acted as blocks to elongation of nascent strands, but gradually lost that ability over a 10 h period after exposure to 10 J/m 2 . The work reported herein attempted to examine possible cell cycle mediated alterations in the recovery of DNA synthesis. Kinetic incorporation of radiolabeled thymidine studies indicated that there may have been a more rapid recover of DNA synthesis in cells irradiated in G 1 or G 2 vs cells irradiated in S phase. DNA fiber autoradiograms prepared from synchronous cells indicated that after irradiation in any phase of the cell cycle, the length of newly synthesized DNA was equal to control lengths 1 h after exposure to 5.0Jm 2 (or 1 h after entering S phase for cells irradiated in G 1 or G 2 ). This observed recovery was not solely due to an excision process. No cell cycle mediated difference in the number of dimers induced or removed as a function of cell cycle position was observed. These results appear to be consistent with a continuum of effects, with initiation effects dominating the response at low fluences, gapped synthesis at intermediate fluences and elongation inhibition at high fluences. The fluences at which each event dominates may be cell-line specific. (author)

Synthesis of ammonia using sodium melt

OpenAIRE

Kawamura, Fumio; Taniguchi, Takashi

2017-01-01

Research into inexpensive ammonia synthesis has increased recently because ammonia can be used as a hydrogen carrier or as a next generation fuel which does not emit CO2. Furthermore, improving the efficiency of ammonia synthesis is necessary, because current synthesis methods emit significant amounts of CO2. To achieve these goals, catalysts that can effectively reduce the synthesis temperature and pressure, relative to those required in the Haber-Bosch process, are required. Although severa...

[Epigenetic alterations in acute lymphoblastic leukemia].

Science.gov (United States)

Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin.

Science.gov (United States)

Wilson, Fiona A; Orellana, Renán A; Suryawan, Agus; Nguyen, Hanh V; Jeyapalan, Asumthia S; Frank, Jason; Davis, Teresa A

2008-07-01

Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7-10 days of pST (150 microg x kg(-1) x day(-1)) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 microU/ml), 2) fed control (25 microU/ml), and 3) fed pST-treated (50 microU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1.eIF4E complex association and increased active eIF4E.eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation.

Physical processes of magmatism and effects on the potential repository: Synthesis of technical work through Fiscal Year 1995

Energy Technology Data Exchange (ETDEWEB)

Valentine, G.A.

1996-09-01

This chapter summarizes data collection and model calculations through FY 95 under Study Plan 8.3.1.8.1.2 Physical Processes of Magmatism and Effects on the Potential Repository. The focus of this study plan is to gather information that ultimately constrains the consequences of small-volume, basaltic magmatic activity at or near a potential repository. This is then combined with event probability estimates, described elsewhere in this synthesis report, to yield a magmatic risk assessment. Tere are two basic classes of effects of magmatisms that are considered here: (1) Eruptive effects, whereby rising magma intersects a potential repository, entrains radioactive waste, and erupts it onto the earth`s surface. (2) Subsurface effects, which includes a wide range of processes such as hydrothermal flow, alteration of mineral assemblages in the potential repository system, and alteration of hydrologic flow properties of the rocks surrounding a potential repository.

Physical processes of magmatism and effects on the potential repository: Synthesis of technical work through Fiscal Year 1995

International Nuclear Information System (INIS)

Valentine, G.A.

1996-01-01

This chapter summarizes data collection and model calculations through FY 95 under Study Plan 8.3.1.8.1.2 Physical Processes of Magmatism and Effects on the Potential Repository. The focus of this study plan is to gather information that ultimately constrains the consequences of small-volume, basaltic magmatic activity at or near a potential repository. This is then combined with event probability estimates, described elsewhere in this synthesis report, to yield a magmatic risk assessment. Tere are two basic classes of effects of magmatisms that are considered here: (1) Eruptive effects, whereby rising magma intersects a potential repository, entrains radioactive waste, and erupts it onto the earth's surface. (2) Subsurface effects, which includes a wide range of processes such as hydrothermal flow, alteration of mineral assemblages in the potential repository system, and alteration of hydrologic flow properties of the rocks surrounding a potential repository

Synthesis of 19-substituted geldanamycins with altered conformations and their binding to heat shock protein Hsp90

Science.gov (United States)

Kitson, Russell R. A.; Chang, Chuan-Hsin; Xiong, Rui; Williams, Huw E. L.; Davis, Adrienne L.; Lewis, William; Dehn, Donna L.; Siegel, David; Roe, S. Mark; Prodromou, Chrisostomos; Ross, David; Moody, Christopher J.

2013-01-01

The benzoquinone ansamycin geldanamycin and its derivatives are inhibitors of heat shock protein Hsp90, an emerging target for novel therapeutic agents both in cancer and in neurodegeneration. However, toxicity of these compounds to normal cells has been ascribed to reaction with thiol nucleophiles at the quinone 19-position. We reasoned that blocking this position would ameliorate toxicity, and that it might also enforce a favourable conformational switch of the trans-amide group into the cis-form required for protein binding. We report here an efficient synthesis of such 19-substituted compounds and realization of our hypotheses. Protein crystallography established that the new compounds bind to Hsp90 with, as expected, a cis-amide conformation. Studies on Hsp90 inhibition in cells demonstrated the molecular signature of Hsp90 inhibitors: decreases in client proteins with compensatory increases in other heat shock proteins in both human breast cancer and dopaminergic neural cells, demonstrating their potential for use in the therapy of cancer or neurodegenerative diseases. PMID:23511419

Formal synthesis of naturally occurring norephedrine

Indian Academy of Sciences (India)

A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives has been achieved following classical organic transformations using commercially available chiral pools. The said derivatives were explored for the synthesis of naturally occurring bio-active small molecules. Formal synthesis of norephedrine, virolin ...

Biomimetic and Bioinspired Synthesis of Nanomaterials/Nanostructures.

Science.gov (United States)

Zan, Guangtao; Wu, Qingsheng

2016-03-16

In recent years, due to its unparalleled advantages, the biomimetic and bioinspired synthesis of nanomaterials/nanostructures has drawn increasing interest and attention. Generally, biomimetic synthesis can be conducted either by mimicking the functions of natural materials/structures or by mimicking the biological processes that organisms employ to produce substances or materials. Biomimetic synthesis is therefore divided here into "functional biomimetic synthesis" and "process biomimetic synthesis". Process biomimetic synthesis is the focus of this review. First, the above two terms are defined and their relationship is discussed. Next different levels of biological processes that can be used for process biomimetic synthesis are compiled. Then the current progress of process biomimetic synthesis is systematically summarized and reviewed from the following five perspectives: i) elementary biomimetic system via biomass templates, ii) high-level biomimetic system via soft/hard-combined films, iii) intelligent biomimetic systems via liquid membranes, iv) living-organism biomimetic systems, and v) macromolecular bioinspired systems. Moreover, for these five biomimetic systems, the synthesis procedures, basic principles, and relationships are discussed, and the challenges that are encountered and directions for further development are considered. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Principles of asymmetric synthesis

CERN Document Server

Gawley, Robert E; Aube, Jeffrey

2012-01-01

The world is chiral. Most of the molecules in it are chiral, and asymmetric synthesis is an important means by which enantiopure chiral molecules may be obtained for study and sale. Using examples from the literature of asymmetric synthesis, this book presents a detailed analysis of the factors that govern stereoselectivity in organic reactions. After an explanation of the basic physical-organic principles governing stereoselective reactions, the authors provide a detailed, annotated glossary of stereochemical terms. A chapter on "Practical Aspects of Asymmetric Synthesis" provides a critical overview of the most common methods for the preparation of enantiomerically pure compounds, techniques for analysis of stereoisomers using chromatographic, spectroscopic, and chiroptical methods. The authors then present an overview of the most important methods in contemporary asymmetric synthesis organized by reaction type. Thus, there are four chapters on carbon-carbon bond forming reactions, one chapter on reductions...

Herbicide effects on freshwater benthic diatoms: Induction of nucleus alterations and silica cell wall abnormalities

International Nuclear Information System (INIS)

Debenest, T.; Silvestre, J.; Coste, M.; Delmas, F.; Pinelli, E.

2008-01-01

Benthic diatoms are well known bio-indicators of river pollution by nutrients (nitrogen and phosphorus). Biological indexes, based on diatom sensitivity for non-toxic pollution, have been developed to assess the water quality. Nevertheless, they are not reliable tools to detect pollution by pesticides. Many authors have suggested that toxic agents, like pesticides, induce abnormalities of the diatom cell wall (frustule). High abnormal frustule abundances have been reported in natural diatom communities sampled in streams contaminated by pesticides. However, no direct link was found between the abundances of abnormal frustules in these communities and the pesticide concentrations in stream water. In the present study, a freshwater benthic diatom community, isolated from natural biofilm and cultured under controlled conditions, was treated with a known genotoxic herbicide, maleic hydrazide (MH). Cells were exposed to three concentrations of MH (5 x 10 -6 , 10 -6 , 10 -7 M) for 6 h followed by a 24 h-recovery time. After MH treatments, nucleus alterations were observed: abnormal nucleus location, micronucleus, multinuclear cell or disruption of the nuclear membrane. A dose-dependent increase of nuclear alterations was observed. The difference between the control (9.65 nuclear alterations per 1000 cells observed (9.65 per mille ), S.D. = 4.23) and the highest concentrations (29.40 per mille , S.D. = 8.49 for 10 -6 M and 35.96 per mille , S.D. = 3.71 for 5 x 10 -6 M) was statistically significant (Tukey test, P -6 and 5 x 10 -6 M; Tukey test, P < 0.05). These two parameters tended to increase together (Pearson correlation = 0.702, P < 0.05). The results suggest that the induction of abnormal frustules could be associated with the genotoxic effects of MH. The alterations observed could be related to the effects of MH on the synthesis of the proteins involved in frustule formation or in the regulation of the cytoskeleton of the diatom cells

Feature-aware natural texture synthesis

KAUST Repository

Wu, Fuzhang

2014-12-04

This article presents a framework for natural texture synthesis and processing. This framework is motivated by the observation that given examples captured in natural scene, texture synthesis addresses a critical problem, namely, that synthesis quality can be affected adversely if the texture elements in an example display spatially varied patterns, such as perspective distortion, the composition of different sub-textures, and variations in global color pattern as a result of complex illumination. This issue is common in natural textures and is a fundamental challenge for previously developed methods. Thus, we address it from a feature point of view and propose a feature-aware approach to synthesize natural textures. The synthesis process is guided by a feature map that represents the visual characteristics of the input texture. Moreover, we present a novel adaptive initialization algorithm that can effectively avoid the repeat and verbatim copying artifacts. Our approach improves texture synthesis in many images that cannot be handled effectively with traditional technologies.

The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

Science.gov (United States)

Miettinen, T A; Gylling, H; Nissinen, M J

2011-10-01

To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis.

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Bon Jeong Ku

Full Text Available The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6 is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+Mig-6(f/f; Mig-6(d/d. Mig-6(d/d mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d mice compared to Mig-6(f/f controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.

The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis

Energy Technology Data Exchange (ETDEWEB)

Kirchdoerfer, Robert N.; Moyer, Crystal L.; Abelson, Dafna M.; Saphire, Erica Ollmann (Scripps)

2016-10-18

Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures of the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis.

What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis

Science.gov (United States)

Schick-Makaroff, Kara; MacDonald, Marjorie; Plummer, Marilyn; Burgess, Judy; Neander, Wendy

2016-01-01

Background When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use ‘research synthesis’ as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. Methods We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. Results We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. Conclusions The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers. PMID:29546155

What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis.

Directory of Open Access Journals (Sweden)

Kara Schick-Makaroff

2016-03-01

Full Text Available Background: When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use ‘research synthesis’ as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. Methods: We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. Results: We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. Conclusions: The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers.

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis

Directory of Open Access Journals (Sweden)

Megan M. Cartwright

2016-10-01

Full Text Available Inhalation of multiwalled carbon nanotubes (MWCNTs during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH. Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25 µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous and severe (Gclm null GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.

Hamiltonian Algorithm Sound Synthesis

OpenAIRE

大矢, 健一

2013-01-01

Hamiltonian Algorithm (HA) is an algorithm for searching solutions is optimization problems. This paper introduces a sound synthesis technique using Hamiltonian Algorithm and shows a simple example. "Hamiltonian Algorithm Sound Synthesis" uses phase transition effect in HA. Because of this transition effect, totally new waveforms are produced.

Collaboration and Productivity in Scientific Synthesis

Science.gov (United States)

Hampton, Stephanie E.; Parker, John N.

2011-01-01

Scientific synthesis has transformed ecological research and presents opportunities for advancements across the sciences; to date, however, little is known about the antecedents of success in synthesis. Building on findings from 10 years of detailed research on social interactions in synthesis groups at the National Center for Ecological Analysis…

Evidence that cytochrome b5 acts as a redox donor in CYP17A1 mediated androgen synthesis

International Nuclear Information System (INIS)

Duggal, Ruchia; Liu, Yilin; Gregory, Michael C.; Denisov, Ilia G.; Kincaid, James R.; Sligar, Stephen G.

2016-01-01

Cytochrome P450 17A1 (CYP17A1) is an important drug target for castration resistant prostate cancer. It is a bi-functional enzyme, catalyzing production of glucocorticoid precursors by hydroxylation of pregnene-nucleus, and androgen biosynthesis by a second C−C lyase step, at the expense of glucocorticoid production. Cytochrome b 5 (cyt b 5 ) is known to be a key regulator of the androgen synthesis reaction in vivo, by a mechanism that is not well understood. Two hypotheses have been proposed for the mechanism by which cyt b 5 increases androgen biosynthesis. Cyt b 5 could act as an allosteric effector, binding to CYP17A1 and either changing its selective substrate affinity or altering the conformation of the P450 to increase the catalytic rate or decrease unproductive uncoupling channels. Alternatively, cyt b 5 could act as a redox donor for supply of the second electron in the P450 cycle, reducing the oxyferrous complex to form the reactive peroxo-intermediate. To understand the mechanism of lyase enhancement by cyt b 5 , we generated a redox-inactive form of cyt b 5 , in which the heme is replaced with a Manganese-protoporphyrin IX (Mn-b 5 ), and investigated enhancement of androgen producing lyase reaction by CYP17A1. Given the critical significance of a stable membrane anchor for all of the proteins involved and the need for controlled stoichiometric ratios, we employed the Nanodisc system for this study. The redox inactive form was observed to have no effect on the lyase reaction, while reactions with the normal heme-iron containing cyt b 5 were enhanced ∼5 fold as compared to reactions in the absence of cyt b 5 . We also performed resonance Raman measurements on ferric CYP17A1 bound to Mn-b 5 . Upon addition of Mn-b 5 to Nanodisc reconstituted CYP17A1, we observed clear evidence for the formation of a b 5 -CYP17A1 complex, as noted by changes in the porphyrin modes and alteration in the proximal Fe−S vibrational frequency. Thus, although Mn-b 5 binds

Perspective: Toward "synthesis by design": Exploring atomic correlations during inorganic materials synthesis

Science.gov (United States)

Soderholm, L.; Mitchell, J. F.

2016-05-01

Synthesis of inorganic extended solids is a critical starting point from which real-world functional materials and their consequent technologies originate. However, unlike the rich mechanistic foundation of organic synthesis, with its underlying rules of assembly (e.g., functional groups and their reactivities), the synthesis of inorganic materials lacks an underpinning of such robust organizing principles. In the latter case, any such rules must account for the diversity of chemical species and bonding motifs inherent to inorganic materials and the potential impact of mass transport on kinetics, among other considerations. Without such assembly rules, there is less understanding, less predictive power, and ultimately less control of properties. Despite such hurdles, developing a mechanistic understanding for synthesis of inorganic extended solids would dramatically impact the range of new material discoveries and resulting new functionalities, warranting a broad call to explore what is possible. Here we discuss our recent approaches toward a mechanistic framework for the synthesis of bulk inorganic extended solids, in which either embryonic atomic correlations or fully developed phases in solutions or melts can be identified and tracked during product selection and crystallization. The approach hinges on the application of high-energy x-rays, with their penetrating power and large Q-range, to explore reaction pathways in situ. We illustrate this process using two examples: directed assembly of Zr clusters in aqueous solution and total phase awareness during crystallization from K-Cu-S melts. These examples provide a glimpse of what we see as a larger vision, in which large scale simulations, data-driven science, and in situ studies of atomic correlations combine to accelerate materials discovery and synthesis, based on the assembly of well-defined, prenucleated atomic correlations.

Surfactant-free synthesis of hierarchical niobic acid microflowers assembled from ultrathin nanosheets with efficient photoactivities

Energy Technology Data Exchange (ETDEWEB)

Dong, Wenhao [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 (Singapore); Singapore-Peking University Research Centre, Centre for Research Excellence & Technological Enterprise (CREATE), Singapore, 138602 (Singapore); Pan, Feng, E-mail: phypf2012@163.com [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 (Singapore); Singapore-Peking University Research Centre, Centre for Research Excellence & Technological Enterprise (CREATE), Singapore, 138602 (Singapore); Wang, Yanyan [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 (Singapore); Singapore-Peking University Research Centre, Centre for Research Excellence & Technological Enterprise (CREATE), Singapore, 138602 (Singapore); Xiao, Shuning [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 (Singapore); International Joint Lab on Resource Chemistry SHNU-NUS-PU, Department of Chemistry, Shanghai Normal University, Shanghai 200234 (China); Wu, Kai [Singapore-Peking University Research Centre, Centre for Research Excellence & Technological Enterprise (CREATE), Singapore, 138602 (Singapore); BNLMS, SKLSCUSS, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 (China); Xu, Guo Qin [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543 (Singapore); Singapore-Peking University Research Centre, Centre for Research Excellence & Technological Enterprise (CREATE), Singapore, 138602 (Singapore); National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Jiangsu Prov., 215123 (China); and others

2017-01-15

Highlights: • 3D hierarchical niobic acid microflower was synthesized by a surfactant-free method. • The microflower was composed of ultrathin nanosheets with ∼5 nm thickness. • The microflower showed high photoactivity owing to the 3D structural features. • This microflower was converted to Nb{sub 2}O{sub 5} without significant structural alteration. • Nb{sub 2}O{sub 5} nanoneedles can also be obtained by adjusting the pH value during synthesis. - Abstract: Hierarchical niobic acid (Nb{sub 2}O{sub 5}·nH{sub 2}O) microflowers are synthesized by a surfactant-free hydrothermal approach. The three-dimensional microflowers are assembled from two-dimensional ultrathin nanosheets with thickness of ∼5 nm. Using rhodamine B as a probe, the Nb{sub 2}O{sub 5}·nH{sub 2}O microflowers exhibit high photocatalytic activity under UV light irradiation. Furthermore, the Nb{sub 2}O{sub 5}·nH{sub 2}O microflowers are easily converted to niobium pentoxide without significant structural alteration.

Interplay between Selenium Levels and Replicative Senescence in WI-38 Human Fibroblasts: A Proteomic Approach.

Science.gov (United States)

Hammad, Ghania; Legrain, Yona; Touat-Hamici, Zahia; Duhieu, Stéphane; Cornu, David; Bulteau, Anne-Laure; Chavatte, Laurent

2018-01-20

Selenoproteins are essential components of antioxidant defense, redox homeostasis, and cell signaling in mammals, where selenium is found in the form of a rare amino acid, selenocysteine. Selenium, which is often limited both in food intake and cell culture media, is a strong regulator of selenoprotein expression and selenoenzyme activity. Aging is a slow, complex, and multifactorial process, resulting in a gradual and irreversible decline of various functions of the body. Several cellular aspects of organismal aging are recapitulated in the replicative senescence of cultured human diploid fibroblasts, such as embryonic lung fibroblast WI-38 cells. We previously reported that the long-term growth of young WI-38 cells with high (supplemented), moderate (control), or low (depleted) concentrations of selenium in the culture medium impacts their replicative lifespan, due to rapid changes in replicative senescence-associated markers and signaling pathways. In order to gain insight into the molecular link between selenium levels and replicative senescence, in the present work, we have applied a quantitative proteomic approach based on 2-Dimensional Differential in-Gel Electrophoresis (2D-DIGE) to the study of young and presenescent cells grown in selenium-supplemented, control, or depleted media. Applying a restrictive cut-off (spot intensity ±50% and a p value iii) spots varying in response to selenium concentration in presenescent cells. Interestingly, a 72% overlap between the impact of senescence and selenium was observed in our proteomic results, demonstrating a strong interplay between selenium, selenoproteins, and replicative senescence.

Plasma selenium concentrations are sufficient and associated with protease inhibitor use in treated HIV-infected adults

Science.gov (United States)

Background: Selenium (Se) is an essential constituent of selenoproteins which play significant roles in antioxidant defense and inflammatory cascades. Selenium deficiency is associated with disease states characterized by inflammation including cardiovascular disease (CVD). While HIV infection has b...

Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans

NARCIS (Netherlands)

Verloop, H.; Dekkers, O.M.; Peeters, R.P.; Schoones, J.W.; Smit, J.W.

2014-01-01

Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple

A microsystem to evaluate the synthesis of [3H]leucine labeled proteins by macrophages

International Nuclear Information System (INIS)

Varesio, L.; Eva, A.

1980-01-01

A method is described for evaluating protein synthesis by adherent MPHI by measuring the incorporation of [ 3 H]leucine into TCA precipitable material. By using guanidine-HCl it was possible to remove completely the radiolabeled proteins from the adherent cells that were cultured in microwells, and retain TCA precipitable material. This procedure enabled the authors to harvest the TCA precipitable proteins with a semiautomatic cell harvester. The guanidine-HCl treatment did not affect the recovery of the radioactive proteins and did not alter the sensitivity of the assay. This method is very simple and rapid and, since it is suitable for processing microcultures, permits detailed studies on the biology of small numbers of MPHI. (Auth.)

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

Directory of Open Access Journals (Sweden)

Frans Stellaard

2017-01-01

Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

Science.gov (United States)

Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas D E; Rozen, Rima

2015-03-01

Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Folic acid-supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr(+/+) and Mthfr(+/-) mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr(+/-) mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr(+/-) livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr(+/-) mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot

Green chemistry for nanoparticle synthesis.

Science.gov (United States)

Duan, Haohong; Wang, Dingsheng; Li, Yadong

2015-08-21

The application of the twelve principles of green chemistry in nanoparticle synthesis is a relatively new emerging issue concerning the sustainability. This field has received great attention in recent years due to its capability to design alternative, safer, energy efficient, and less toxic routes towards synthesis. These routes have been associated with the rational utilization of various substances in the nanoparticle preparations and synthetic methods, which have been broadly discussed in this tutorial review. This article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present several pivotal aspects of synthesis with environmental concerns, involving the selection and evaluation of nontoxic capping and reducing agents, the choice of innocuous solvents and the development of energy-efficient synthetic methods.

Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis

Energy Technology Data Exchange (ETDEWEB)

Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J.; Anderson, Charles T.

2015-11-02

Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis.

High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

Directory of Open Access Journals (Sweden)

Eui Seok Shin

Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

Demonstration of diet-induced decoupling of fatty acid and cholesterol synthesis by combining gene expression array and 2H2O quantification.

Science.gov (United States)

Jensen, Kristian K; Previs, Stephen F; Zhu, Lei; Herath, Kithsiri; Wang, Sheng-Ping; Bhat, Gowri; Hu, Guanghui; Miller, Paul L; McLaren, David G; Shin, Myung K; Vogt, Thomas F; Wang, Liangsu; Wong, Kenny K; Roddy, Thomas P; Johns, Douglas G; Hubbard, Brian K

2012-01-15

The liver is a crossroad for metabolism of lipid and carbohydrates, with acetyl-CoA serving as an important metabolic intermediate and a precursor for fatty acid and cholesterol biosynthesis pathways. A better understanding of the regulation of these pathways requires an experimental approach that provides both quantitative metabolic flux measurements and mechanistic insight. Under conditions of high carbohydrate availability, excess carbon is converted into free fatty acids and triglyceride for storage, but it is not clear how excessive carbohydrate availability affects cholesterol biosynthesis. To address this, C57BL/6J mice were fed either a low-fat, high-carbohydrate diet or a high-fat, carbohydrate-free diet. At the end of the dietary intervention, the two groups received (2)H(2)O to trace de novo fatty acid and cholesterol synthesis, and livers were collected for gene expression analysis. Expression of lipid and glucose metabolism genes was determined using a custom-designed pathway focused PCR-based gene expression array. The expression analysis showed downregulation of cholesterol biosynthesis genes and upregulation of fatty acid synthesis genes in mice receiving the high-carbohydrate diet compared with the carbohydrate-free diet. In support of these findings, (2)H(2)O tracer data showed that fatty acid synthesis was increased 10-fold and cholesterol synthesis was reduced by 1.6-fold in mice fed the respective diets. In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered.

Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268.

Science.gov (United States)

Kimoto, Sohei; Bazmi, H Holly; Lewis, David A

2014-09-01

Cognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia. The authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes. GAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes. Deficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia.

Synthesis of ammonia using sodium melt.

Science.gov (United States)

Kawamura, Fumio; Taniguchi, Takashi

2017-09-14

Research into inexpensive ammonia synthesis has increased recently because ammonia can be used as a hydrogen carrier or as a next generation fuel which does not emit CO 2 . Furthermore, improving the efficiency of ammonia synthesis is necessary, because current synthesis methods emit significant amounts of CO 2 . To achieve these goals, catalysts that can effectively reduce the synthesis temperature and pressure, relative to those required in the Haber-Bosch process, are required. Although several catalysts and novel ammonia synthesis methods have been developed previously, expensive materials or low conversion efficiency have prevented the displacement of the Haber-Bosch process. Herein, we present novel ammonia synthesis route using a Na-melt as a catalyst. Using this route, ammonia can be synthesized using a simple process in which H 2 -N 2 mixed gas passes through the Na-melt at 500-590 °C under atmospheric pressure. Nitrogen molecules dissociated by reaction with sodium then react with hydrogen, resulting in the formation of ammonia. Because of the high catalytic efficiency and low-cost of this molten-Na catalyst, it provides new opportunities for the inexpensive synthesis of ammonia and the utilization of ammonia as an energy carrier and next generation fuel.

Detonation Synthesis of Alpha-Variant Silicon Carbide

Science.gov (United States)

Langenderfer, Martin; Johnson, Catherine; Fahrenholtz, William; Mochalin, Vadym

2017-06-01

A recent research study has been undertaken to develop facilities for conducting detonation synthesis of nanomaterials. This process involves a familiar technique that has been utilized for the industrial synthesis of nanodiamonds. Developments through this study have allowed for experimentation with the concept of modifying explosive compositions to induce synthesis of new nanomaterials. Initial experimentation has been conducted with the end goal being synthesis of alpha variant silicon carbide (α-SiC) in the nano-scale. The α-SiC that can be produced through detonation synthesis methods is critical to the ceramics industry because of a number of unique properties of the material. Conventional synthesis of α-SiC results in formation of crystals greater than 100 nm in diameter, outside nano-scale. It has been theorized that the high temperature and pressure of an explosive detonation can be used for the formation of α-SiC in the sub 100 nm range. This paper will discuss in detail the process development for detonation nanomaterial synthesis facilities, optimization of explosive charge parameters to maximize nanomaterial yield, and introduction of silicon to the detonation reaction environment to achieve first synthesis of nano-sized alpha variant silicon carbide.

Comparison of the Rate and Extent of Deoxyribonucleic Acid Repair and Semi-Conservative Synthesis in Bacteria Exposed to Ultra-Violet Light

Energy Technology Data Exchange (ETDEWEB)

Billen, D. [Radiation Biology Laboratory and Departments of Microbiology and Radiology, College of Medicine, University of Florida, Gainesville, FL (United States)

1968-08-15

Many bacterial strains possess the ability to repair genetic damage resulting from ultra-violet light (u.v. ) exposure. Of major importance is the occurrence of a 'repair' type of deoxyribonucleic acid (DNA) replication during 'dark repair', which presumably results in the replacement of the damaged portion of the genome. With deuterium, {sup 15}N and {sup 13}C as a density label, and buoyant density centrifugation in CsCl as a means of separating pre and post-irradiation synthesized DNA strands, the rate and extent of DNA repair synthesis in exponential - phase Escherichia coli strain B/r were determined. After u.v. exposure, {sup 3}H-thymine incorporation into the 'heavy' parental DNA strands was used to measure repair synthesis, while {sup 3}H-thymine incorporation into 'light' and newly synthesized DNA strands measured semi-conservative replication. The rate of bases incorporated by repair synthesis in the initial 15 minures of post-irradiation incubation at 37 Degree-Sign C appears to be saturated at a dose of approximately 100 ergs/mm{sup 2}. At higher doses (up to 600 ergs/mm{sup 2}) the increase observed was not proportional to dose. During this initial 15 minutes, less than 1% of the chromosomal DNA was replaced. The amount of DNA synthesized by semi-conservative replication during the initial 15 minutes was reduced with increasing u.v. dose. After exposure to 600 ergs/mm{sup 2}, repair and semiconservative DNA synthesis were nearly equivalent in the irradiated cells after 15 minutes of incubation. Repair synthesis was observed to be terminated by 45 minutes in bacteria exposed to 160 or 500 ergs/mm{sup 2} (64% and 10% survivors, respectively). The amount of genome replaced by repair synthesis at several doses was determined. Starvation for a required amino acid (resulting in an inhibition of protein and ribonucleic acid synthesis) did not prevent the repair synthesis nor grossly alter its extent. The restoration of the semi-conservative mo d e of DNA

An alter-centric perspective on employee innovation: The importance of alters' creative self-efficacy and network structure.

Science.gov (United States)

Grosser, Travis J; Venkataramani, Vijaya; Labianca, Giuseppe Joe

2017-09-01

While most social network studies of employee innovation behavior examine the focal employees' ("egos'") network structure, we employ an alter-centric perspective to study the personal characteristics of employees' network contacts-their "alters"-to better understand employee innovation. Specifically, we examine how the creative self-efficacy (CSE) and innovation behavior of employees' social network contacts affects their ability to generate and implement novel ideas. Hypotheses were tested using a sample of 144 employees in a U.S.-based product development organization. We find that the average CSE of alters in an employee's problem solving network is positively related to that employee's innovation behavior, with this relationship being mediated by these alters' average innovation behavior. The relationship between the alters' average innovation behavior and the employee's own innovation behavior is strengthened when these alters have less dense social networks. Post hoc results suggest that having network contacts with high levels of CSE also leads to an increase in ego's personal CSE 1 year later in cases where the employee's initial level of CSE was relatively low. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Rambutan peels promoted biomimetic synthesis of bioinspired zinc oxide nanochains for biomedical applications

Science.gov (United States)

Yuvakkumar, R.; Suresh, J.; Saravanakumar, B.; Joseph Nathanael, A.; Hong, Sun Ig; Rajendran, V.

2015-02-01

A naturally occurring rambutan peel waste was employed to synthesis bioinspired zinc oxide nanochains. Rambutan peels has the ability of ligating zinc ions as a natural ligation agent resulting in zinc oxide nanochains formation due to its extended polyphenolic system over incubation period. Successful formation of zinc oxide nanochains was confirmed employing transmission electron microscopy studies. About 60% and ∼40% cell viability was lost and 50% and 10% morphological change was observed in 7 and 4 days incubated ZnO treated cells compared with control. Moreover, 50% and 55% of cell death was observed at 24 and 48 h incubation with 7 days treated ZnO cells and hence alters and disturbs the growth of cancer cells and could be used for liver cancer cell treatment.

Synthesis of oligonucleotide phosphorodithioates

DEFF Research Database (Denmark)

Beaton, G.; Brill, W. K D; Grandas, A.

1991-01-01

The synthesis of DNA containing sulfur at the two nonbonding internucleotide valencies is reported. Several different routes using either tervalent or pentavalent mononucleotide synthons are described.......The synthesis of DNA containing sulfur at the two nonbonding internucleotide valencies is reported. Several different routes using either tervalent or pentavalent mononucleotide synthons are described....

Mechanisms and assessment of statin-related muscular adverse effects

Science.gov (United States)

Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

2014-01-01

Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis

DEFF Research Database (Denmark)

Doessing, Simon; Heinemeier, Katja M; Holm, Lars

2010-01-01

young individuals. rhGH administration caused an increase in serum GH, serum IGF-I, and IGF-I mRNA expression in tendon and muscle. Tendon collagen I mRNA expression and tendon collagen protein synthesis increased by 3.9-fold and 1.3-fold, respectively (P ...RNA expression and muscle collagen protein synthesis increased by 2.3-fold and 5.8-fold, respectively (P protein synthesis was unaffected by elevation of GH and IGF-I. Moderate exercise did not enhance the effects of GH manipulation. Thus, increased GH availability stimulates...... matrix collagen synthesis in skeletal muscle and tendon, but without any effect upon myofibrillar protein synthesis. The results suggest that GH is more important in strengthening the matrix tissue than for muscle cell hypertrophy in adult human musculotendinous tissue....

STICS: surface-tethered iterative carbohydrate synthesis.

Science.gov (United States)

Pornsuriyasak, Papapida; Ranade, Sneha C; Li, Aixiao; Parlato, M Cristina; Sims, Charles R; Shulga, Olga V; Stine, Keith J; Demchenko, Alexei V

2009-04-14

A new surface-tethered iterative carbohydrate synthesis (STICS) technology is presented in which a surface functionalized 'stick' made of chemically stable high surface area porous gold allows one to perform cost efficient and simple synthesis of oligosaccharide chains; at the end of the synthesis, the oligosaccharide can be cleaved off and the stick reused for subsequent syntheses.

Finding the K best synthesis plans.

Science.gov (United States)

Fagerberg, Rolf; Flamm, Christoph; Kianian, Rojin; Merkle, Daniel; Stadler, Peter F

2018-04-05

In synthesis planning, the goal is to synthesize a target molecule from available starting materials, possibly optimizing costs such as price or environmental impact of the process. Current algorithmic approaches to synthesis planning are usually based on selecting a bond set and finding a single good plan among those induced by it. We demonstrate that synthesis planning can be phrased as a combinatorial optimization problem on hypergraphs by modeling individual synthesis plans as directed hyperpaths embedded in a hypergraph of reactions (HoR) representing the chemistry of interest. As a consequence, a polynomial time algorithm to find the K shortest hyperpaths can be used to compute the K best synthesis plans for a given target molecule. Having K good plans to choose from has many benefits: it makes the synthesis planning process much more robust when in later stages adding further chemical detail, it allows one to combine several notions of cost, and it provides a way to deal with imprecise yield estimates. A bond set gives rise to a HoR in a natural way. However, our modeling is not restricted to bond set based approaches-any set of known reactions and starting materials can be used to define a HoR. We also discuss classical quality measures for synthesis plans, such as overall yield and convergency, and demonstrate that convergency has a built-in inconsistency which could render its use in synthesis planning questionable. Decalin is used as an illustrative example of the use and implications of our results.

Synthesis and characterization of CdS/PVA nanocomposite films

Science.gov (United States)

Wang, Hongmei; Fang, Pengfei; Chen, Zhe; Wang, Shaojie

2007-08-01

A series CdS/PVA nanocomposite films with different amount of Cd salt have been prepared by means of the in situ synthesis method via the reaction of Cd 2+-dispersed poly vinyl-alcohol (PVA) with H 2S. The as-prepared films were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) absorption, photoluminescence (PL) spectra, Fourier transform infrared spectroscope (FTIR) and thermogravimetric analysis (TGA). The XRD results indicated the formation of CdS nanoparticles with hexagonal phase in the PVA matrix. The primary FTIR spectra of CdS/PVA nanocomposite in different processing stages have been discussed. The vibrational absorption peak of Cd sbnd S bond at 405 cm -1 was observed, which further testified the generation of CdS nanoparticles. The TGA results showed incorporation of CdS nanoparticles significantly altered the thermal properties of PVA matrix. The photoluminescence and UV-vis spectroscopy revealed that the CdS/PVA films showed quantum confinement effect.

Synthesis and characterization of CdS/PVA nanocomposite films

International Nuclear Information System (INIS)

Wang Hongmei; Fang Pengfei; Chen Zhe; Wang Shaojie

2007-01-01

A series CdS/PVA nanocomposite films with different amount of Cd salt have been prepared by means of the in situ synthesis method via the reaction of Cd 2+ -dispersed poly vinyl-alcohol (PVA) with H 2 S. The as-prepared films were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) absorption, photoluminescence (PL) spectra, Fourier transform infrared spectroscope (FTIR) and thermogravimetric analysis (TGA). The XRD results indicated the formation of CdS nanoparticles with hexagonal phase in the PVA matrix. The primary FTIR spectra of CdS/PVA nanocomposite in different processing stages have been discussed. The vibrational absorption peak of Cd-S bond at 405 cm -1 was observed, which further testified the generation of CdS nanoparticles. The TGA results showed incorporation of CdS nanoparticles significantly altered the thermal properties of PVA matrix. The photoluminescence and UV-vis spectroscopy revealed that the CdS/PVA films showed quantum confinement effect

Fuels planning: science synthesis and integration; fact sheet: The Fuels Synthesis Project overview

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

The geographic focus of the "Fuels Planning: Science Synthesis and Integration" project #known as the Fuels Synthesis Project# is on the dry forests of the Western United States. Target audiences include fuels management specialists, resource specialists, National Environmental Policy Act #NEPA# planning team leaders, line officers in the USDA Forest Service...

Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

Science.gov (United States)

Lambertenghi-Deliliers, G; Zanon, P L; Pozzoli, E F; Bellini, O; Praga, C

1978-02-28

The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

Synthesis in land change science

DEFF Research Database (Denmark)

Magliocca, Nicholas R.; Rudel, Thomas K.; Verburg, Peter H.

2015-01-01

Global and regional economic and environmental changes are increasingly influencing local land-use, livelihoods, and ecosystems. At the same time, cumulative local land changes are driving global and regional changes in biodiversity and the environment. To understand the causes and consequences...... of these changes, land change science (LCS) draws on a wide array synthetic and meta-study techniques to generate global and regional knowledge from local case studies of land change. Here, we review the characteristics and applications of synthesis methods in LCS and assess the current state of synthetic research...... based on a meta-analysis of synthesis studies from 1995 to 2012. Publication of synthesis research is accelerating, with a clear trend toward increasingly sophisticated and quantitative methods, including meta-analysis. Detailed trends in synthesis objectives, methods, and land change phenomena...

Altered synthesis of some secretory proteins in pancreatic lobules isolated from streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Duan, R.D.; Erlanson-Albertsson, C.

1990-01-01

The in vitro incorporation of [35S]cysteine into lipase, colipase, amylase, procarboxypeptidase A and B, and the serine proteases and total proteins was studied in pancreatic lobules isolated from normal and diabetic rats with or without insulin treatment. The incorporation of [35S]cysteine into total proteins was 65% greater in pancreatic lobules from diabetic animals than from normal rats. The increased incorporation was partly reversed by insulin treatment (2 U/100 g/day for 5 days) of diabetic rats. The relative rates of biosynthesis for amylase and the procarboxypeptidases in diabetic pancreatic lobules were decreased by 75 and 25%, respectively, after 1 h of incubation, while those for lipase, colipase, and the serine proteases were increased by 90, 85, and 35%, respectively. The absolute rates of synthesis for these enzymes changed in the same direction as the relative rates in diabetic lobules, except that for the procarboxypeptidases, which did not change. The changed rates of biosynthesis for the pancreatic enzymes were reversed by insulin treatment of the diabetic rats. Kinetic studies showed that the incorporation of [35S]cysteine into amylase, lipase, and colipase was linear until up to 2 h of incubation in normal pancreatic lobules, while in the diabetic lobules the incorporation into lipase and colipase was accelerated, reaching a plateau level already after 1 h of incubation. It is concluded that the biosynthesis of pancreatic secretory proteins in diabetic rats is greatly changed both in terms of quantity and kinetics

Rate in template-directed polymer synthesis.

Science.gov (United States)

Saito, Takuya

2014-06-01

We discuss the temporal efficiency of template-directed polymer synthesis, such as DNA replication and transcription, under a given template string. To weigh the synthesis speed and accuracy on the same scale, we propose a template-directed synthesis (TDS) rate, which contains an expression analogous to that for the Shannon entropy. Increasing the synthesis speed accelerates the TDS rate, but the TDS rate is lowered if the produced sequences are diversified. We apply the TDS rate to some production system models and investigate how the balance between the speed and the accuracy is affected by changes in the system conditions.

Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

Directory of Open Access Journals (Sweden)

Alessandra Mirtes Marques Neves Gonçalves

2014-07-01

Full Text Available Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.

Straightforward high-pressure synthesis and characterization of indium-based thiospinels: photocatalytic potential for hydrogen production

Energy Technology Data Exchange (ETDEWEB)

Falcon, Horacio [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco (Spain); NANOTEC (Centro de Investigacion en Nanociencia y Nanotecnologia), Universidad Tecnologica Nacional-Facultad Regional Cordoba, Cordoba (Argentina); Tartaj, Pedro; Alonso, Jose Antonio [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco (Spain); Vaquero, Fernando; Navarro, Rufino M.; Fierro, Jose Luis G. [Instituto de Catalisis y Petroleoquimica, CSIC, Cantoblanco, Madrid (Spain); Bolletta, Juan P.; Paoli, Juan M. de; Carbonio, Raul E. [INFIQC - CONICET, Departamento de Fisicoquimica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba (Argentina); Fernandez-Diaz, Maria Teresa [Institut Laue Langevin, Grenoble (France)

2016-04-15

Ternary chalcogenides (AB{sub 2}X{sub 4}) based on the spinel structure are gaining a great deal of attention because of the possibility of tuning their magnetic and optoelectronic properties not only by changing chemical composition but also by altering their degree of inversion. Here we report a rapid high-pressure synthetic method for the synthesis of MIn{sub 2}S{sub 4} powders starting from commercially available solid sulfides. We prove the versatility of our method by reporting the synthesis of six members of the MIn{sub 2}S{sub 4} family (M = Mn, Fe, Co, Ni, Zn, and Cd) under high-pressure conditions (3.5 GPa); these compounds show complete to moderate degrees of inversion. Furthermore, this family covers a spectral region that includes visible band gaps. Interestingly, the structural refinement carried out by X-ray and neutron diffraction allows one to establish positive correlations between the gap and different parameters, including the degree of inversion. Finally, as a proof-of-concept, these ternary chalcogenides show moderate photocatalytic hydrogen production from aqueous solutions. (Copyright copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Evidence that cytochrome b{sub 5} acts as a redox donor in CYP17A1 mediated androgen synthesis

Energy Technology Data Exchange (ETDEWEB)

Duggal, Ruchia [Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL (United States); Liu, Yilin [Department of Chemistry, Marquette University, Milwaukee, WI (United States); Gregory, Michael C.; Denisov, Ilia G. [Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL (United States); Kincaid, James R. [Department of Chemistry, Marquette University, Milwaukee, WI (United States); Sligar, Stephen G., E-mail: s-sligar@illinois.edu [Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL (United States); Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL (United States)

2016-08-19

Cytochrome P450 17A1 (CYP17A1) is an important drug target for castration resistant prostate cancer. It is a bi-functional enzyme, catalyzing production of glucocorticoid precursors by hydroxylation of pregnene-nucleus, and androgen biosynthesis by a second C−C lyase step, at the expense of glucocorticoid production. Cytochrome b{sub 5} (cyt b{sub 5}) is known to be a key regulator of the androgen synthesis reaction in vivo, by a mechanism that is not well understood. Two hypotheses have been proposed for the mechanism by which cyt b{sub 5} increases androgen biosynthesis. Cyt b{sub 5} could act as an allosteric effector, binding to CYP17A1 and either changing its selective substrate affinity or altering the conformation of the P450 to increase the catalytic rate or decrease unproductive uncoupling channels. Alternatively, cyt b{sub 5} could act as a redox donor for supply of the second electron in the P450 cycle, reducing the oxyferrous complex to form the reactive peroxo-intermediate. To understand the mechanism of lyase enhancement by cyt b{sub 5}, we generated a redox-inactive form of cyt b{sub 5}, in which the heme is replaced with a Manganese-protoporphyrin IX (Mn-b{sub 5}), and investigated enhancement of androgen producing lyase reaction by CYP17A1. Given the critical significance of a stable membrane anchor for all of the proteins involved and the need for controlled stoichiometric ratios, we employed the Nanodisc system for this study. The redox inactive form was observed to have no effect on the lyase reaction, while reactions with the normal heme-iron containing cyt b{sub 5} were enhanced ∼5 fold as compared to reactions in the absence of cyt b{sub 5}. We also performed resonance Raman measurements on ferric CYP17A1 bound to Mn-b{sub 5}. Upon addition of Mn-b{sub 5} to Nanodisc reconstituted CYP17A1, we observed clear evidence for the formation of a b{sub 5}-CYP17A1 complex, as noted by changes in the porphyrin modes and alteration in the proximal

Inhibition of hyaluronan synthesis reduces versican and fibronectin levels in trabecular meshwork cells.

Directory of Open Access Journals (Sweden)

Kate E Keller

Full Text Available Hyaluronan (HA is a major component of the extracellular matrix (ECM and is synthesized by three HA synthases (HAS. Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU, or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process.

Feeding a high-concentrate corn straw diet induced epigenetic alterations in the mammary tissue of dairy cows.

Directory of Open Access Journals (Sweden)

Guozhong Dong

Full Text Available The objective of this study was to investigate the effects of feeding a high-concentrate corn straw (HCS diet (65% concentrate+35% corn straw on the epigenetic changes in the mammary tissue of dairy cows in comparison with a low-concentrate corn straw (LCS diet (46% concentrate+54% corn straw and with a low-concentrate mixed forage (LMF diet (46% concentrate+54% mixed forage.Multiparous mid-lactation Chinese Holstein cows were fed one of these three diets for 6 weeks, at which time blood samples and mammary tissue samples were collected. Mammary arterial and venous blood samples were analyzed for lipopolysaccharide (LPS concentrations while mammary tissue samples were assayed for histone H3 acetylation and the methylation of specific genes associated with fat and protein synthesis.Extraction of histones and quantification of histone H3 acetylation revealed that acetylation was significantly reduced in cows fed the HCS diet, as compared with cows fed the LCS diet. Cows fed the HCS diet had significantly higher LPS concentrations in the mammary arterial blood, as compared with cows fed the LCS diet. We found that the extent of histone H3 acetylation was negatively correlated with LPS concentrations. The methylation of the stearoyl-coenzyme A desaturase gene associated with milk fat synthesis was increased in cows fed the HCS diet. By contrast, methylation of the gene encoding the signal transducer and activator of transcription 5A was reduced in cows fed the HCS diet, suggesting that feeding a high-concentrate corn straw diet may alter the methylation of specific genes involved in fat and protein synthesis in the mammary tissue of dairy cows.Feeding the high-concentrate diet induced epigenetic changes in the mammary tissues of dairy cows, possibly through effecting the release of differing amounts of LPS into the mammary blood.

CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration

Science.gov (United States)

Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

Science.gov (United States)

Giglio, Anita; Brandmayr, Pietro

2017-08-01

Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

ALTER-GLOBALISM AND DEVELOPMENT IN MIGRATION CONDITIONS. THE CASE OF AN EAST EUROPEAN COUNTRY

Directory of Open Access Journals (Sweden)

Alina HALLER

2017-12-01

Full Text Available Globalisation is a process that brings advantages and disadvantages to all states, regardless of their stage of development. The relative deprivation, especially the financial one, of the developing countries is a reason of frustration, which motivates the emigration decision; hence our orientation to alter-globalism. In this paper, I intend to highlight by means of analysis, synthesis, deduction, induction, and statistic data, the causes and types of migration in Romania’s case, one of the main European countries where the immigrants originate from. We will see how globalisation manifests itself in a twofold manner in the economy and the society of a developing country, just like migration. We will show why a poor country is avoided by immigrants and deserted, as a result of immigration, by its own population, while, just like the developed states, it is likely to face the same demographic, economic and social problems, considering that the process of demographic transition is already manifested.

A kernel version of multivariate alteration detection

DEFF Research Database (Denmark)

Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

2013-01-01

Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations.......Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations....

Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running

Science.gov (United States)

Kato, Hiroyuki; Suzuki, Hiromi; Inoue, Yoshiko; Suzuki, Katsuya; Kobayashi, Hisamine

2016-01-01

Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR) at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control) was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise. PMID:27367725

Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running

Directory of Open Access Journals (Sweden)

Hiroyuki Kato

2016-06-01

Full Text Available Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise.

Members of the LBD family of transcription factors repress anthocyanin synthesis and affect additional nitrogen responses in Arabidopsis.

Science.gov (United States)

Rubin, Grit; Tohge, Takayuki; Matsuda, Fumio; Saito, Kazuki; Scheible, Wolf-Rüdiger

2009-11-01

Nitrogen (N) and nitrate (NO(3)(-)) per se regulate many aspects of plant metabolism, growth, and development. N/NO(3)(-) also suppresses parts of secondary metabolism, including anthocyanin synthesis. Molecular components for this repression are unknown. We report that three N/NO(3)(-)-induced members of the LATERAL ORGAN BOUNDARY DOMAIN (LBD) gene family of transcription factors (LBD37, LBD38, and LBD39) act as negative regulators of anthocyanin biosynthesis in Arabidopsis thaliana. Overexpression of each of the three genes in the absence of N/NO(3)(-) strongly suppresses the key regulators of anthocyanin synthesis PAP1 and PAP2, genes in the anthocyanin-specific part of flavonoid synthesis, as well as cyanidin- but not quercetin- or kaempferol-glycoside production. Conversely, lbd37, lbd38, or lbd39 mutants accumulate anthocyanins when grown in N/NO(3)(-)-sufficient conditions and show constitutive expression of anthocyanin biosynthetic genes. The LBD genes also repress many other known N-responsive genes, including key genes required for NO(3)(-) uptake and assimilation, resulting in altered NO(3)(-) content, nitrate reductase activity/activation, protein, amino acid, and starch levels, and N-related growth phenotypes. The results identify LBD37 and its two close homologs as novel repressors of anthocyanin biosynthesis and N availability signals in general. They also show that, besides being developmental regulators, LBD genes fulfill roles in metabolic regulation.

Investigation of alteration zones in Garandake and Kurokawa

Energy Technology Data Exchange (ETDEWEB)

Kinbara, K [Geological Survey of Japan, Kawasaki; Sudo, S

1977-01-01

The eastern part of the Garan area contains both the Myoban and Tsukahara hot springs. The springs are associated with the Sanin Formation, and an alteration zone is present which strikes easterly. Throughout the altered area, a clear zonation of the alteration is present. The zonation runs: silicified - alunitized - kaolin/argillized - montmorillonite/zeolite. In the Kurokawa area, a total of 0.96 km/sup 2/ of altered zones were observed near Suzumejigoku and throughout Yoshikawa and Tawara. The most heavily altered areas were at Kurokawa hot springs and Yoshikawa, where alunite and kaolinite are abundant. The time of alteration is believed to be prior to the deposition of the Hisazumi pumice. Around the Kurokawa hot springs, where the water temperature is 98/sup 0/C, the alteration extends as far as the pumice.

28 CFR 36.405 - Alterations: Historic preservation.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Historic preservation. 36... Alterations: Historic preservation. (a) Alterations to buildings or facilities that are eligible for listing in the National Register of Historic Places under the National Historic Preservation Act (16 U.S.C...

Radiation protection philosophy alters

International Nuclear Information System (INIS)

Firmin, G.

1977-01-01

Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

Suppression of matrix protein synthesis in endothelial cells by herpes simplex virus is not dependent on viral protein synthesis

International Nuclear Information System (INIS)

Kefalides, N.A.

1986-01-01

The synthesis of matrix proteins by human endothelial cells (EC) in vitro was studied before and at various times after infection with Herpes Simplex virus Type 1 (HSV-1) or 2 (HSV-2). Monolayers of EC were either mock-infected or infected with virus for 1 hr at a multiplicity infection (MOI) of 5 to 20 at 37 0 C. Control and infected cultures were pulse-labeled for 1 or 2 hrs with either [ 14 C]proline or [ 35 S]methionine. Synthesis of labeled matrix proteins was determined by SDS-gel electrophoresis. Suppression of synthesis of fibronectin, Type IV collagen and thrombospondin began as early as 2 hrs and became almost complete by 10 hrs post-infection. The degree of suppression varied with the protein and the virus dose. Suppression of Type IV collagen occurred first followed by that of fibronectin and then thrombospondin. Infection of EC with UV irradiated HSV-1 or HSV-2 resulted in suppression of host-cell protein synthesis as well as viral protein synthesis. Infection with intact virus in the presence of actinomycin-D resulted in suppression of both host-cell and viral protein synthesis. The data indicate that infection of EC with HSV leads to suppression of matrix protein synthesis which does not depend on viral protein synthesis

Rubella virus capsid protein modulation of viral genomic and subgenomic RNA synthesis

International Nuclear Information System (INIS)

Tzeng, W.-P.; Frey, Teryl K.

2005-01-01

The ratio of the subgenomic (SG) to genome RNA synthesized by rubella virus (RUB) replicons expressing the green fluorescent protein reporter gene (RUBrep/GFP) is substantially higher than the ratio of these species synthesized by RUB (4.3 for RUBrep/GFP vs. 1.3-1.4 for RUB). It was hypothesized that this modulation of the viral RNA synthesis was by one of the virus structural protein genes and it was found that introduction of the capsid (C) protein gene into the replicons as an in-frame fusion with GFP resulted in an increase of genomic RNA production (reducing the SG/genome RNA ratio), confirming the hypothesis and showing that the C gene was the moiety responsible for the modulation effect. The N-terminal one-third of the C gene was required for the effect of be exhibited. A similar phenomenon was not observed with the replicons of Sindbis virus, a related Alphavirus. Interestingly, modulation was not observed when RUBrep/GFP was co-transfected with either other RUBrep or plasmid constructs expressing the C gene, demonstrating that modulation could occur only when the C gene was provided in cis. Mutations that prevented translation of the C protein failed to modulate RNA synthesis, indicating that the C protein was the moiety responsible for modulation; consistent with this conclusion, modulation of RNA synthesis was maintained when synonymous codon mutations were introduced at the 5' end of the C gene that changed the C gene sequence without altering the amino acid sequence of the C protein. These results indicate that C protein translated in proximity of viral replication complexes, possibly from newly synthesized SG RNA, participate in regulating the replication of viral RNA

Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects.

Science.gov (United States)

Nagasaka, Hironori; Tsukahara, Hirokazu; Yorifuji, Tohru; Miida, Takashi; Murayama, Kei; Tsuruoka, Tomoko; Takatani, Tomozumi; Kanazawa, Masaki; Kobayashi, Kunihiko; Okano, Yoshiyuki; Takayanagi, Masaki

2009-03-01

Nitric oxide (NO) is synthesized from arginine and O(2) by nitric oxide synthase (NOS). Citrulline, which is formed as a by-product of the NOS reaction, can be recycled to arginine by the 2 enzymes acting in the urea cycle: argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). Although the complete urea cycle is expressed only in the liver, ASS and ASL are expressed in other organs including the kidney and vascular endothelium. To examine possible alterations of the NO pathway in urea cycle defects, we measured plasma concentrations of arginine and citrulline and serum concentrations of nitrite/nitrate (NOx(-), stable NO metabolites) and asymmetric dimethylarginine (ADMA, an endogenous NOS inhibitor) in patients with congenital urea cycle disorders of 3 types: ornithine transcarbamylase (OTC) deficiency, ASS deficiency, and ASL deficiency. All were receiving oral arginine replacement at the time of this study. The same parameters were also measured in healthy subjects, who participated as controls. The OTC-deficient patients had significantly high NOx(-) and nonsignificantly high ADMA concentrations. Their NOx(-) was significantly positively correlated with arginine. The ASS-deficient patients had significantly low NOx(-) and significantly high ADMA concentrations. The ASL-deficient patients had normal NOx(-) and nonsignificantly high ADMA concentrations. In ASS-deficient and ASL-deficient patients, the NOx(-) was significantly inversely correlated with citrulline. These results suggest that NO synthesis is enhanced in OTC-deficient patients while receiving arginine but that NO synthesis remains low in ASS-deficient patients despite receiving arginine. They also suggest that endogenous NO synthesis is negatively affected by citrulline and ADMA in ASS-deficient and ASL-deficient patients. Although the molecular mechanisms remain poorly understood, we infer that the NO pathway might play a role in the pathophysiology related to congenital urea cycle

28 CFR 36.403 - Alterations: Path of travel.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Path of travel. 36.403... Alterations: Path of travel. (a) General. An alteration that affects or could affect the usability of or... the maximum extent feasible, the path of travel to the altered area and the restrooms, telephones, and...

Topology synthesis of large-displacement compliant mechanisms

DEFF Research Database (Denmark)

Pedersen, Claus B. Wittendorf; Buhl, Thomas; Sigmund, Ole

2001-01-01

This paper describes the use of topology optimization as a synthesis tool for the design of large-displacement compliant mechanisms. An objective function for the synthesis of large-displacement mechanisms is proposed together with a formulation for synthesis of path-generating compliant mechanisms...

Music and Alterity Processes

Directory of Open Access Journals (Sweden)

Josep Martí

2014-10-01

Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

Noncovalent synthesis of protein dendrimers

NARCIS (Netherlands)

Lempens, E.H.M.; Baal, van I.; Dongen, van J.L.J.; Hackeng, T.M.; Merkx, M.; Meijer, E.W.

2009-01-01

The covalent synthesis of complex biomolecular systems such as multivalent protein dendrimers often proceeds with low efficiency, thereby making alternative strategies based on noncovalent chemistry of high interest. Here, the synthesis of protein dendrimers using a strong but noncovalent

High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice12345

Science.gov (United States)

Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas DE

2015-01-01

Background: Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Objective: Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Design: Folic acid–supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr+/+ and Mthfr+/− mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Results: Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr+/− mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr+/− livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr+/− mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. Conclusions: We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2

Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats

International Nuclear Information System (INIS)

Femia, Angelo Pietro; Luceri, Cristina; Toti, Simona; Giannini, Augusto; Dolara, Piero; Caderni, Giovanna

2010-01-01

Azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. For gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent). Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 including Apc. The results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a low degree of genomic imbalance, it is interesting to

Organic synthesis with stable isotopes

International Nuclear Information System (INIS)

Blazer, R.M.; Daub, G.H.; Kerr, V.N.; Williams, D.L.; Whaley, T.W.

1982-01-01

Described is a scheme for the synthesis of L-arginine-1- 13 C utilizing methods developed for the synthesis of L-ornithine-1- 13 C from L-ornithine-2- 13 C and then converting ornithine into arginine with the enzyme acylase

Chemical synthesis on SU-8

DEFF Research Database (Denmark)

Qvortrup, Katrine; Taveras, Kennedy; Thastrup, Ole

2011-01-01

In this paper we describe a highly effective surface modification of SU-8 microparticles, the attachment of appropriate linkers for solid-supported synthesis, and the successful chemical modification of these particles via controlled multi-step organic synthesis leading to molecules attached...

AutoBayes Program Synthesis System System Internals

Science.gov (United States)

Schumann, Johann Martin

2011-01-01

This lecture combines the theoretical background of schema based program synthesis with the hands-on study of a powerful, open-source program synthesis system (Auto-Bayes). Schema-based program synthesis is a popular approach toward program synthesis. The lecture will provide an introduction into this topic and discuss how this technology can be used to generate customized algorithms. The synthesis of advanced numerical algorithms requires the availability of a powerful symbolic (algebra) system. Its task is to symbolically solve equations, simplify expressions, or to symbolically calculate derivatives (among others) such that the synthesized algorithms become as efficient as possible. We will discuss the use and importance of the symbolic system for synthesis. Any synthesis system is a large and complex piece of code. In this lecture, we will study Autobayes in detail. AutoBayes has been developed at NASA Ames and has been made open source. It takes a compact statistical specification and generates a customized data analysis algorithm (in C/C++) from it. AutoBayes is written in SWI Prolog and many concepts from rewriting, logic, functional, and symbolic programming. We will discuss the system architecture, the schema libary and the extensive support infra-structure. Practical hands-on experiments and exercises will enable the student to get insight into a realistic program synthesis system and provides knowledge to use, modify, and extend Autobayes.

Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures

Science.gov (United States)

2015-02-09

Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures. Research Area:7.4 The views, opinions and/or findings contained in this report...journals: Final Report: Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular

Selenium Supplementation in Fish: A Combined Chemical and Biomolecular Study to Understand Sel-Plex Assimilation and Impact on Selenoproteome Expression in Rainbow Trout (Oncorhynchus mykiss.

Directory of Open Access Journals (Sweden)

Davide Pacitti

Full Text Available Selenium (Se is an essential oligonutrient, as a component of several Se-containing proteins (selenoproteins, which exert important biological functions within an organism. In livestock, Se-enriched products have been proposed as dietary supplements to be included into functional feeds for animal preventive health care. To this end, it is important to understand the optimal range of concentrations for supplementation and how long it takes to be assimilated into the organism.In this study, rainbow trout (Oncorhynchus mykiss were fed a control diet containing 0.9 g Kg-1 Se or the same diet supplemented with a Se-Yeast product (Sel-Plex to achieve Se concentrations ranging from 1.5-8.9 g Kg-1 for a period of ten weeks. Fish were sampled every two weeks for analysis. The kinetics of Se bioaccumulation and the effects on fish selenoprotein expression was determined in different tissues combining chemical and bimolecular techniques.The Sel-Plex enriched diets did not have any effect on survival and growth performance. The highest Se levels were found in liver and kidney followed by muscle and blood cells. Analysis of the Se concentration factor showed that liver is able to initially regulate the amount of Se accumulated. However, with higher dietary Se level (4.8 and 8.9 g Kg-1 and longer times of exposure (10 weeks, regulation is ineffective and the Se tissue concentration increases. The expression of the selected trout selenoprotein transcripts showed an inverse correlation with Sel-Plex augmentation in most cases. In liver, kidney and blood cells the highest up-regulation of the trout selenoprotein genes was seen mostly in the group fed the diet enriched with the lowest concentration of Sel-Plex (0.5 g Kg-1 for 10 weeks.Sel-Plex may represent an excellent Se supplement to deliver a high level of Se without provoking harm to the fish and to guarantee the maximal absorption of the element. According to our results, a dietary supplementation of Sel

Biological alterations resulting from chronic lung irradiation. II. Connective tissue alterations following inhalation of 144Ce fused clay aerosol in beagle dogs

International Nuclear Information System (INIS)

Pickrell, J.A.; Harris, D.V.; Pfleger, R.C.; Benjamin, S.A.; Belasich, J.J.; Jones, R.K.; McClellan, R.O.

1975-01-01

Beagle dogs were exposed by inhalation to an aerosol of 144 Ce clay to quantitate the relationship between pulmonary radiation dose and induced fibrosis. Collagen, elastin, glucosamine, and the ratios of elastin/collagen, hydroxyproline/hydroxylysine, and hydroxyproline/proline were determined to indicate changes in connective tissue constituents. Total lung collagen was partitioned into native collagen, soluble collagen, and ultrafilterable hydroxyproline peptides. Increased total lung collagen correlated best with increasing cumulative radiation dose and increasing time after inhalation exposure. The increase in total lung collagen was not seen until more than 4 mo after exposure and a cumulative dose of about 40,000 rad. Soluble collagen and low molecular weight hydroxyproline peptide quantities both increased at 2 mo after exposure and cumulative doses of 20,000 to 27,000 rad. A variable elastin response apparently was not related to either increasing time or increasing radiation dose after exposure. These results indicate that collagen accumulation is an important factor in pulmonary fibrosis. Although collagen synthesis and breakdown were both activated at a relatively early time after inhalation, a significant increase in native collagen (scarring) occurred only when the metabolic balance was altered by protracted time or irradiation after exposure. The interrelationships observed in this study provide insight into the mechanism of fibrosis induced by chronic pulmonary injury. (U.S.)

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis.

Science.gov (United States)

Cartwright, Megan M; Schmuck, Stefanie C; Corredor, Charlie; Wang, Bingbing; Scoville, David K; Chisholm, Claire R; Wilkerson, Hui-Wen; Afsharinejad, Zahra; Bammler, Theodor K; Posner, Jonathan D; Shutthanandan, Vaithiyalingam; Baer, Donald R; Mitra, Somenath; Altemeier, William A; Kavanagh, Terrance J

2016-10-01

Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous) and severe (Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels. Copyright © 2016. Published by Elsevier B.V.

Chemo-enzymatic peptide synthesis : bioprocess engineering aspects

NARCIS (Netherlands)

Vossenberg, P.

2012-01-01

Peptides, in particular oligopeptides, play an important role in the fields of health care, nutrition and cosmetics. Chemical synthesis is currently the most mature technique for the synthesis of peptides that range in length from 5 to 80 amino acids. Chemical synthesis is, however,

Organic synthesis

Energy Technology Data Exchange (ETDEWEB)

Thomas, S.E.

1991-01-01

This paper reports on reactions of organoboranes. Organoboron routes to unsaturated hydrocarbons. Boronic ester homologation. Properties of organosilicon compounds. Alkene synthesis (Peterson olefination). Allylsilanes and acylsilanes.

Total synthesis of solanoeclepin A

Science.gov (United States)

Tanino, Keiji; Takahashi, Motomasa; Tomata, Yoshihide; Tokura, Hiroshi; Uehara, Taketo; Narabu, Takashi; Miyashita, Masaaki

2011-06-01

Cyst nematodes are troublesome parasites that live on, and destroy, a range of important host vegetable plants. Damage caused by the potato cyst nematode has now been reported in over 50 countries. One approach to eliminating the problem is to stimulate early hatching of the nematodes, but key hatching stimuli are not naturally available in sufficient quantities to do so. Here, we report the first chemical synthesis of solanoeclepin A, the key hatch-stimulating substance for potato cyst nematode. The crucial steps in our synthesis are an intramolecular cyclization reaction for construction of the highly strained tricyclo[5.2.1.01,6]decane skeleton (DEF ring system) and an intramolecular Diels-Alder reaction of a furan derivative for the synthesis of the ABC carbon framework. The present synthesis has the potential to contribute to addressing one of the critical food issues of the twenty-first century.

Modulation of protein synthesis by polyamines.

Science.gov (United States)

Igarashi, Kazuei; Kashiwagi, Keiko

2015-03-01

Polyamines are ubiquitous small basic molecules that play important roles in cell growth and viability. Since polyamines mainly exist as a polyamine-RNA complex, we looked for proteins whose synthesis is preferentially stimulated by polyamines at the level of translation, and thus far identified 17 proteins in Escherichia coli and 6 proteins in eukaryotes. The mechanisms of polyamine stimulation of synthesis of these proteins were investigated. In addition, the role of eIF5A, containing hypusine formed from spermidine, on protein synthesis is described. These results clearly indicate that polyamines and eIF5A contribute to cell growth and viability through modulation of protein synthesis. © 2015 International Union of Biochemistry and Molecular Biology.

The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis.

Directory of Open Access Journals (Sweden)

Robert N Kirchdoerfer

2016-10-01

Full Text Available Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP, a phosphoprotein (VP35 and a polymerase (L. However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures of the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis.

Synthesis of nano-sized amorphous boron powders through active dilution self-propagating high-temperature synthesis method

Energy Technology Data Exchange (ETDEWEB)

Wang, Jilin [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Gu, Yunle [School of Material Science and Engineering, Wuhan Institute of Technology, Wuhan 430073 (China); Li, Zili [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Wang, Weimin, E-mail: wangwm@hotmail.com [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China); Fu, Zhengyi [The State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070 (China)

2013-06-01

Graphical abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed. Highlights: ► Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis method. ► The morphology, particle size and purity of the samples could be effectively controlled via changing the endothermic rate. ► The diluter KBH{sub 4} played an important role in active dilution synthesis of amorphous nano-sized boron powders. ► The active dilution method could be further popularized and become a common approach to prepare various inorganic materials. - Abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method at temperatures ranging from 700 °C to 850 °C in a SHS furnace using Mg, B{sub 2}O{sub 3} and KBH{sub 4} as raw materials. Samples were characterized by X-ray powder diffraction (XRD), Laser particle size analyzer, Fourier transform infrared spectra (FTIR), X-ray energy dispersive spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission TEM (HRTEM). The boron powders demonstrated an average particle size of 50 nm with a purity of 95.64 wt.%. The diluter KBH{sub 4} played an important role in the active dilution synthesis of amorphous nano-sized boron powders. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed.

Synthesis of nano-sized amorphous boron powders through active dilution self-propagating high-temperature synthesis method

International Nuclear Information System (INIS)

Wang, Jilin; Gu, Yunle; Li, Zili; Wang, Weimin; Fu, Zhengyi

2013-01-01

Graphical abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed. Highlights: ► Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis method. ► The morphology, particle size and purity of the samples could be effectively controlled via changing the endothermic rate. ► The diluter KBH 4 played an important role in active dilution synthesis of amorphous nano-sized boron powders. ► The active dilution method could be further popularized and become a common approach to prepare various inorganic materials. - Abstract: Nano-sized amorphous boron powders were synthesized by active dilution self-propagating high-temperature synthesis (SHS) method at temperatures ranging from 700 °C to 850 °C in a SHS furnace using Mg, B 2 O 3 and KBH 4 as raw materials. Samples were characterized by X-ray powder diffraction (XRD), Laser particle size analyzer, Fourier transform infrared spectra (FTIR), X-ray energy dispersive spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission TEM (HRTEM). The boron powders demonstrated an average particle size of 50 nm with a purity of 95.64 wt.%. The diluter KBH 4 played an important role in the active dilution synthesis of amorphous nano-sized boron powders. The effects of endothermic reaction rate, the possible chemical reaction mechanism and active dilution model for synthesis of the product were also discussed

Synthesis of 2-phosphaadamantane derivatives

International Nuclear Information System (INIS)

Zemlyanoi, V.N.; Aleksandrov, A.M.; Kukhar', V.P.

1986-01-01

The authors describe the synthesis and properties of 2-phosphadamantane derivatives. For the synthesis of 2-phosphaadamantane derivatives they decided to use the methodology of the synthesis of 2-thiaadamantane. The IR spectra were determined on CHCl 3 solutions with a Specord 711R spectrometer, the PMR spectra were determined on Tesla BS-467 (60 MHz) and Bruker WP-200 (200 MHz) spectrometers, external standard hexamethyldisiloxane, the 31 P NMR spectra were determined on Tesla BS-487 C (30 MHz) and Bruker WP-200 (81 MHz) spectrometers, external standard 85% phosphoric acid, and the mass spectra were determined on an MS-1302 spectrometer

Divergent solid-phase synthesis of natural product-inspired bipartite cyclodepsipeptides : total synthesis of seragamide A

NARCIS (Netherlands)

Arndt, H.-D.; Rizzo, S.; Nöcker, Chr.; Wackchaure, V.N.; Milroy, L.G.; Bieker, V.; Calderon, A.; Tran, T.T.N.; Brand, S.; Dehmelt, L.; Waldmann, H.

2015-01-01

Macrocyclic natural products (NPs) and analogues thereof often show high affinity, selectivity, and metabolic stability, and methods for the synthesis of NP-like macrocycle collections are of major current interest. We report an efficient solid-phase/cyclorelease method for the synthesis of a

Nitrocyclopropanes: synthesis and properties

Energy Technology Data Exchange (ETDEWEB)

Averina, Elena B; Yashin, N V; Kuznetsova, Tamara S; Zefirov, Nikolai S [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)

2009-10-31

State-of-the-art data on the methods of synthesis, properties and transformations of nitro- and- dinitrocyclopropanes of different structure is generalized and described systematically. The attention is focused on stereoselective cyclopropanation methods, new approaches to the synthesis of natural products and their synthetic analogues with diversified biological activities, in particular, of aminocyclopropane acids based on nitrocyclopropanes, and the formation of structures of energetic compounds.

ATP-binding cassette B10 regulates early steps of heme synthesis.

Science.gov (United States)

Bayeva, Marina; Khechaduri, Arineh; Wu, Rongxue; Burke, Michael A; Wasserstrom, J Andrew; Singh, Neha; Liesa, Marc; Shirihai, Orian S; Langer, Nathaniel B; Paw, Barry H; Ardehali, Hossein

2013-07-19

Heme plays a critical role in gas exchange, mitochondrial energy production, and antioxidant defense in cardiovascular system. The mitochondrial transporter ATP-binding cassette (ABC) B10 has been suggested to export heme out of the mitochondria and is required for normal hemoglobinization of erythropoietic cells and protection against ischemia-reperfusion injury in the heart; however, its primary function has not been established. The aim of this study was to identify the function of ABCB10 in heme synthesis in cardiac cells. Knockdown of ABCB10 in cardiac myoblasts significantly reduced heme levels and the activities of heme-containing proteins, whereas supplementation with δ-aminolevulinic acid reversed these defects. Overexpression of mitochondrial δ-aminolevulinic acid synthase 2, the rate-limiting enzyme upstream of δ-aminolevulinic acid export, failed to restore heme levels in cells with ABCB10 downregulation. ABCB10 and heme levels were increased by hypoxia, and reversal of ABCB10 upregulation caused oxidative stress and cell death. Furthermore, ABCB10 knockdown in neonatal rat cardiomyocytes resulted in a significant delay of calcium removal from the cytoplasm, suggesting a relaxation defect. Finally, ABCB10 expression and heme levels were altered in failing human hearts and mice with ischemic cardiomyopathy. ABCB10 plays a critical role in heme synthesis pathway by facilitating δ-aminolevulinic acid production or export from the mitochondria. In contrast to previous reports, we show that ABCB10 is not a heme exporter and instead is required for the early mitochondrial steps of heme biosynthesis.

Matrix-assisted peptide synthesis on nanoparticles.

Science.gov (United States)

Khandadash, Raz; Machtey, Victoria; Weiss, Aryeh; Byk, Gerardo

2014-09-01

We report a new method for multistep peptide synthesis on polymeric nanoparticles of differing sizes. Polymeric nanoparticles were functionalized via their temporary embedment into a magnetic inorganic matrix that allows multistep peptide synthesis. The matrix is removed at the end of the process for obtaining nanoparticles functionalized with peptides. The matrix-assisted synthesis on nanoparticles was proved by generating various biologically relevant peptides. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Sustainable processes synthesis for renewable resources

International Nuclear Information System (INIS)

Halasz, L.; Povoden, G.; Narodoslawsky, M.

2005-01-01

Renewable resources pose special challenges to process synthesis. Due to decentral raw material generation, usually low transport densities and the perishable character of most renewable raw materials in combination with their time dependent availability, logistical questions as well as adaptation to regional agricultural structures are necessary. This calls for synthesis of structures not only of single processes but of the whole value chain attached to the utilisation of a certain resource. As most of the innovative technologies proposed to build on a renewable raw material base face stiff economic competition from fossil based processes, economic optimality of the value chain is crucial to their implementation. On top of this widening of the process definition for synthesis, many processes on the base of renewable resources apply technologies (like membrane separations, chromatographic purification steps, etc.) for which the heuristic knowledge is still slim. This reduces the choice of methods for process synthesis, mainly to methods based on combinatorial principles. The paper investigates applicability as well as impact on technology development of process synthesis for renewable raw material utilisation. It takes logistic considerations into account and applies process synthesis to the case study of the green biorefinery concept. The results show the great potential of process synthesis for technology development of renewable resource utilisation. Applied early in the development phase, it can point towards the most promising utilisation pathways, thus guiding the engineering work. On top of that, and even more important, it can help avoid costly development flops as it also clearly indicates 'blind alleys' that have to be avoided

Cell-specific monitoring of protein synthesis in vivo.

Directory of Open Access Journals (Sweden)

Nikos Kourtis

Full Text Available Analysis of general and specific protein synthesis provides important information, relevant to cellular physiology and function. However, existing methodologies, involving metabolic labelling by incorporation of radioactive amino acids into nascent polypeptides, cannot be applied to monitor protein synthesis in specific cells or tissues, in live specimens. We have developed a novel approach for monitoring protein synthesis in specific cells or tissues, in vivo. Fluorescent reporter proteins such as GFP are expressed in specific cells and tissues of interest or throughout animals using appropriate promoters. Protein synthesis rates are assessed by following fluorescence recovery after partial photobleaching of the fluorophore at targeted sites. We evaluate the method by examining protein synthesis rates in diverse cell types of live, wild type or mRNA translation-defective Caenorhabditis elegans animals. Because it is non-invasive, our approach allows monitoring of protein synthesis in single cells or tissues with intrinsically different protein synthesis rates. Furthermore, it can be readily implemented in other organisms or cell culture systems.

Block of glucocorticoid synthesis during re-activation inhibits extinction of an established fear memory.

Science.gov (United States)

Blundell, Jacqueline; Blaiss, Cory A; Lagace, Diane C; Eisch, Amelia J; Powell, Craig M

2011-05-01

The pharmacology of traumatic memory extinction has not been fully characterized despite its potential as a therapeutic target for established, acquired anxiety disorders, including post-traumatic stress disorder (PTSD). Here we examine the role of endogenous glucocorticoids in traumatic memory extinction. Male C57BL/6J mice were injected with corticosterone (10 mg/kg, i.p.) or metyrapone (50 mg/kg, s.c.) during re-activation of a contextual fear memory, and compared to vehicle groups (N=10-12 per group). To ensure that metyrapone was blocking corticosterone synthesis, we measured corticosterone levels following re-activation of a fear memory in metyrapone- and vehicle-treated animals. Corticosterone administration following extinction trials caused a long-lasting inhibition of the original fear memory trace. In contrast, blockade of corticosteroid synthesis with metyrapone prior to extinction trials enhanced retrieval and prevented extinction of context-dependent fear responses in mice. Further behavioral analysis suggested that the metyrapone enhancement of retrieval and prevention of extinction were not due to non-specific alterations in locomotor or anxiety-like behavior. In addition, the inhibition of extinction by metyrapone was rescued by exogenous administration of corticosterone following extinction trials. Finally, we confirmed that the rise in corticosterone during re-activation of a contextual fear memory was blocked by metyrapone. We demonstrate that extinction of a classical contextual fear memory is dependent on endogenous glucocorticoid synthesis during re-activation of a fear memory. Our data suggest that decreased glucocorticoids during fear memory re-activation may contribute to the inability to extinguish a fear memory, thus contributing to one of the core symptoms of PTSD. Copyright © 2011 Elsevier Inc. All rights reserved.

Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

Energy Technology Data Exchange (ETDEWEB)

Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

2013-02-01

Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

Herbicide effects on freshwater benthic diatoms: Induction of nucleus alterations and silica cell wall abnormalities

Energy Technology Data Exchange (ETDEWEB)

Debenest, T. [Ecolab UMR 5245 (INP ENSAT, CNRS, UPS), Equipe ECOGEN, Avenue de l' Agrobiopole - BP 32607 Auzeville Tolosane, 31326 Castanet Tolosan Cedex (France); Cemagref, 50 avenue de Verdun, 33612 Cestas Cedex (France); Silvestre, J. [Ecolab UMR 5245 (INP ENSAT, CNRS, UPS), Equipe ECOGEN, Avenue de l' Agrobiopole - BP 32607 Auzeville Tolosane, 31326 Castanet Tolosan Cedex (France); Coste, M.; Delmas, F. [Cemagref, 50 avenue de Verdun, 33612 Cestas Cedex (France); Pinelli, E. [Ecolab UMR 5245 (INP ENSAT, CNRS, UPS), Equipe ECOGEN, Avenue de l' Agrobiopole - BP 32607 Auzeville Tolosane, 31326 Castanet Tolosan Cedex (France)], E-mail: pinelli@ensat.fr

2008-06-02

effects of MH. The alterations observed could be related to the effects of MH on the synthesis of the proteins involved in frustule formation or in the regulation of the cytoskeleton of the diatom cells.

Sustainable Process Synthesis-Intensification

DEFF Research Database (Denmark)

Babi, Deenesh Kavi; Holtbruegge, Johannes; Lutze, Philip

2014-01-01

Sustainable process design can be achieved by performing process synthesis and process intensification together. This approach first defines a design target through a sustainability analysis and then finds design alternatives that match the target through process intensification. A systematic......, multi-stage framework for process synthesis- intensification that identifies more sustainable process designs has been developed. At stages 1-2, the working scale is at the level of unit operations, where a base case design is identified and analyzed with respect to sustainability metrics. At stages 3......, a phenomena-based process synthesis method is applied, where the phenomena involved in each tasks are identified, manipulated and recombined to generate new and/or existing unit operations configured into flowsheets that are more sustainable from those found in the previous levels. An overview of the key...

Impaired synthesis and antioxidant defense of glutathione in the cerebellum of autistic subjects: alterations in the activities and protein expression of glutathione-related enzymes.

Science.gov (United States)

Gu, Feng; Chauhan, Ved; Chauhan, Abha

2013-12-01

Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence in autism suggests a deficit in glutathione (GSH), a major endogenous antioxidant. It is not known whether the synthesis, consumption, and/or regeneration of GSH is affected in autism. In the cerebellum tissues from autism (n=10) and age-matched control subjects (n=10), the activities of GSH-related enzymes glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), and glutamate cysteine ligase (GCL) involved in antioxidant defense, detoxification, GSH regeneration, and synthesis, respectively, were analyzed. GCL is a rate-limiting enzyme for GSH synthesis, and the relationship between its activity and the protein expression of its catalytic subunit GCLC and its modulatory subunit GCLM was also compared between the autistic and the control groups. Results showed that the activities of GPx and GST were significantly decreased in autism compared to that of the control group (Pautistic subjects showed lower GR activity than 95% confidence interval (CI) of the control group. GCL activity was also significantly reduced by 38.7% in the autistic group compared to the control group (P=0.023), and 8 of 10 autistic subjects had values below 95% CI of the control group. The ratio of protein levels of GCLC to GCLM in the autism group was significantly higher than that of the control group (P=0.022), and GCLM protein levels were reduced by 37.3% in the autistic group compared to the control group. A positive strong correlation was observed between GCL activity and protein levels of GCLM (r=0.887) and GCLC (r=0.799) subunits in control subjects but not in autistic subjects, suggesting that regulation of GCL activity is affected in autism. These results suggest that enzymes involved in GSH homeostasis have impaired activities in the cerebellum in autism, and lower GCL activity in autism may be related to decreased protein expression

UV light-induced DNA synthesis arrest in HeLa cells is associated with changes in phosphorylation of human single-stranded DNA-binding protein

International Nuclear Information System (INIS)

Carty, M.P.; Zernik-Kobak, M.; McGrath, S.; Dixon, K.

1994-01-01

We show that DNA replication activity in extracts of human HeLa cells decreases following UV irradiation. Alterations in replication activity in vitro parallel the UV-induced block in cell cycle progression of these cells in culture. UV irradiation also induces specific changes in the pattern of phosphorylation of the 34 kDa subunit of a DNA replication protein, human single-stranded DNA-binding protein (hSSB). The appearance of a hyperphosphorylated form of hSSB correlates with reduced in vitro DNA replication activity in extracts of UV-irradiated cells. Replication activity can be restored to these extracts in vitro by addition of purified hSSB. These results suggest that UV-induced DNA synthesis arrest may be mediated in part through phosphorylation-related alterations in the activity of hSSB, an essential component of the DNA replication apparatus. (Author)

Tributyltin impaired reproductive success in female zebrafish through disrupting oogenesis, reproductive behaviors and serotonin synthesis.

Science.gov (United States)

Xiao, Wei-Yang; Li, Ying-Wen; Chen, Qi-Liang; Liu, Zhi-Hao

2018-07-01

Tributyltin (TBT), an organotin acting as aromatase (Cyp19a1) inhibitor, has been found to disrupt gametogenesis and reproductive behaviors in several fish species. However, few studies addressing the mechanisms underlying the impaired gametogenesis and reproduction have been reported. In this study, female adults of zebrafish (Danio rerio) were continuously exposed to two nominal concentrations of TBT (100 and 500 ng/L, actual concentrations: 90.8 ± 1.3 ng/L and 470.3 ± 2.7 ng/L, respectively) for 28 days. After exposures, TBT decreased the total egg number, reduced the hatchability and elevated the mortality of the larvae. Decreased gonadosomatic index (GSI) and altered percentages of follicles in different developmental stages (increased early-stage follicles and reduced mid/late-stage follicles) were also observed in the ovary of TBT-treated fish. TBT also lowered the plasma level of 17β-estradiol and suppressed the expressions of cyp19a1a in the ovary. In treated fish, up-regulated expressions of aldhla2, sycp3 and dmc1 were present in the ovary, indicating an enhanced level of meiosis. The mRNA level of vtg1 was dramatically suppressed in the liver of TBT-treated fish, suggesting an insufficient synthesis of Vtg protein, consistent with the decreased percentage of mid/late-stage follicles in the ovaries. Moreover, TBT significantly suppressed the reproductive behaviors of the female fish (duration of both sexes simultaneously in spawning area, the frequency of meeting and the visit in spawning area) and down-regulated the mRNA levels of genes involved in the regulation of reproductive behaviors (cyp19a1b, gnrh-3 and kiss 2) in the brain. In addition, TBT significantly suppressed the expressions of serotonin-related genes, such as tph2 (encoding serotonin synthase), pet1 (marker of serotonin neuron) and kiss 1 (the modulator of serotonin synthesis), suggesting that TBT might disrupt the non-reproductive behaviors of zebrafish. The present

Low-intensity infrared lasers alter actin gene expression in skin and muscle tissue

International Nuclear Information System (INIS)

Fonseca, A S; Mencalha, A L; Campos, V M A; Ferreira-Machado, S C; Peregrino, A A F; Magalhães, L A G; Geller, M; Paoli, F

2013-01-01

The biostimulative effect of low-intensity lasers is the basis for treatment of diseases in soft tissues. However, data about the influence of biostimulative lasers on gene expression are still scarce. The aim of this work was to evaluate the effects of low-intensity infrared lasers on the expression of actin mRNA in skin and muscle tissue. Skin and muscle tissue of Wistar rats was exposed to low-intensity infrared laser radiation at different fluences and frequencies. One and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis and evaluation of actin gene expression by quantitative polymerase chain reaction. The data obtained show that laser radiation alters the expression of actin mRNA differently in skin and muscle tissue of Wistar rats depending of the fluence, frequency and time after exposure. The results could be useful for laser dosimetry, as well as to justify the therapeutic protocols for treatment of diseases of skin and muscle tissues based on low-intensity infrared laser radiation. (paper)

Leucine stimulation of skeletal muscle protein synthesis

International Nuclear Information System (INIS)

Layman, D.K.; Grogan, C.K.

1986-01-01

Previous work in this laboratory has demonstrated a stimulatory effect of leucine on skeletal muscle protein synthesis measured in vitro during catabolic conditions. Studies in other laboratories have consistently found this effect in diaphragm muscle, however, studies examining effects on nitrogen balance or with in vivo protein synthesis in skeletal muscle are equivocal. This experiment was designed to determine the potential of leucine to stimulate skeletal muscle protein synthesis in vivo. Male Sprague-Dawley rats weighing 200 g were fasted for 12 hrs, anesthetized, a jugular cannula inserted, and protein synthesis measured using a primed continuous infusion of 14 C-tyrosine. A plateau in specific activity was reached after 30 to 60 min and maintained for 3 hrs. The leucine dose consisted of a 240 umole priming dose followed by a continuous infusion of 160 umoles/hr. Leucine infusion stimulated protein synthesis in the soleus muscle (28%) and in the red (28%) and white portions (12%) of the gastrocnemius muscle compared with controls infused with only tyrosine. The increased rates of protein synthesis were due to increased incorporation of tyrosine into protein and to decreased specific activity of the free tyrosine pool. These data indicate that infusion of leucine has the potential to stimulate in vivo protein synthesis in skeletal muscles

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

Science.gov (United States)

Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

2016-01-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

Immunization alters body odor.

Science.gov (United States)

Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

2014-04-10

Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

Selenium supplementation for patients with Graves’ hyperthyroidism (the GRASS trial)

DEFF Research Database (Denmark)

Watt, Torquil; Cramon, Per; Bjorner, Jakob Bue

2013-01-01

Graves' hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects...

Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

International Nuclear Information System (INIS)

Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

2013-01-01

Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

Integrated methanol synthesis

International Nuclear Information System (INIS)

Jaeger, W.

1982-01-01

This invention concerns a plant for methanol manufacture from gasified coal, particularly using nuclear power. In order to reduce the cost of the hydrogen circuits, the methanol synthesis is integrated in the coal gasification plant. The coal used is gasified with hydration by means of hydrogen and the crude gas emerging, after cooling and separating the carbon dioxide and hydrogen sulphide, is mixed with the synthetic gas leaving the methane cracking furnace. This mixture is taken to the methanol synthesis and more than 90% is converted into methanol in one pass. The gas mixture remaning after condensation and separation of methanol is decomposed into three fractions in low temperature gas decomposition with a high proportion of unconverted carbon monoxide. The flow of methane is taken to the cracking furnace with steam, the flow of hydrogen is taken to the hydrating coal gasifier, and the flow of carbon monoxide is taken to the methanol synthesis. The heat required for cracking the methane can either be provided by a nuclear reactor or by the coke left after hydrating gasification. (orig./RB) [de

Total Synthesis of Bryostatins. Development of Methodology for Atom-Economic and Stereoselective Synthesis of the C-ring Subunit

Science.gov (United States)

Trost, Barry M.; Frontier, Alison J.; Thiel, Oliver R.; Yang, Hanbiao; Dong, Guangbin

2012-01-01

Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for stereoselective assembly of the C-ring subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the C-ring subunit of bryostatins. PMID:21793057

Simplified analytical methods for the measurement of the synthesis rate of plasma proteins in vivo by the (/sup 14/C)carbonate method

Energy Technology Data Exchange (ETDEWEB)

Caine, S [Glasgow Royal Infirmary (UK); Fleck, A [Charing Cross Hospital, London (UK). Medical School

1984-09-01

A method is described for obtaining the specific activity of /sup 14/C in urea, essential in the measurement of the synthesis rate of a plasma protein in vivo, which is simpler than the original procedure. The principle is the measurement of /sup 14/CO/sub 2/ and NH/sub 4//sup +/ separately, after incubation with urease. A simple alteration gives samples of /sup 13/CO/sub 2/ for mass spectrometry. The 'recoveries' of /sup 14/C and /sup 13/C in urea were invariably between 90 and 96% and the CV was 3%.

A concise synthesis of the cortistatin core

OpenAIRE

Dai, Mingji; Danishefsky, Samuel J.

2008-01-01

We describe a concise and convergent route to the core matrix of the cortistatin steroidal alkaloids. The salient features of the synthesis are the Snieckus cascade methodology and the Masamune alkylative dearomatization. This chemistry lends itself to a total synthesis of the cortistatins and to the development of a SAR program based on diverted total synthesis.

Synthesis of S-linked oligoxylans

DEFF Research Database (Denmark)

Bonora, Beatrice

by several families of enzymes,collected under the name of Glycosyl Hydrolases (GHs). Among other methods,the use of enzyme inhibitors like thio-linked oligosaccharides has for a long timebeen a common tool to analyze and characterize these enzymes.In the present work the chemical synthesis of thio......-analogs of xylo- andarabinoxyloglycans is presented. Furthermore, the selection of a reliable method forthe incorporation of thiolinkages in the synthesis of oligoxylans is alsoinvestigated.Therefore, different strategies for assembling S-linked-disaccharides have beenapproached both involving 1-thioglycoside...... donors and thioacceptors. Advantagesand disadvantages concerning the different methods are described and evaluated inrelation to the synthesis of linear and branched oligoxylans....

A novel synthesis of hemispherands

NARCIS (Netherlands)

Ostaszewski, Ryszard; Verboom, Willem; Reinhoudt, David

1992-01-01

A novel, flexible synthesis of hemispherands {2,5,8-trioxa[9](3,3″) m-terphenylophanes 5a-d} with different central aromatic groups is described. The key step comprises the introduction of the central aromatic ring in the last step of the synthesis via a Suzuki cross-coupling reaction using

Industrial scale gene synthesis.

Science.gov (United States)

Notka, Frank; Liss, Michael; Wagner, Ralf

2011-01-01

The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery. Copyright © 2011 Elsevier Inc. All rights reserved.

Ca-Fe and Alkali-Halide Alteration of an Allende Type B CAI: Aqueous Alteration in Nebular or Asteroidal Settings

Science.gov (United States)

Ross, D. K.; Simon, J. I.; Simon, S. B.; Grossman, L.

2012-01-01

Ca-Fe and alkali-halide alteration of CAIs is often attributed to aqueous alteration by fluids circulating on asteroidal parent bodies after the various chondritic components have been assembled, although debate continues about the roles of asteroidal vs. nebular modification processes [1-7]. Here we report de-tailed observations of alteration products in a large Type B2 CAI, TS4 from Allende, one of the oxidized subgroup of CV3s, and propose a speculative model for aqueous alteration of CAIs in a nebular setting. Ca-Fe alteration in this CAI consists predominantly of end-member hedenbergite, end-member andradite, and compositionally variable, magnesian high-Ca pyroxene. These phases are strongly concentrated in an unusual "nodule" enclosed within the interior of the CAI (Fig. 1). The Ca, Fe-rich nodule superficially resembles a clast that pre-dated and was engulfed by the CAI, but closer inspection shows that relic spinel grains are enclosed in the nodule, and corroded CAI primary phases interfinger with the Fe-rich phases at the nodule s margins. This CAI also contains abundant sodalite and nepheline (alkali-halide) alteration that occurs around the rims of the CAI, but also penetrates more deeply into the CAI. The two types of alteration (Ca-Fe and alkali-halide) are adjacent, and very fine-grained Fe-rich phases are associated with sodalite-rich regions. Both types of alteration appear to be replacive; if that is true, it would require substantial introduction of Fe, and transport of elements (Ti, Al and Mg) out of the nodule, and introduction of Na and Cl into alkali-halide rich zones. Parts of the CAI have been extensively metasomatized.

Serotonin induces ecdysteroidogenesis and methyl farnesoate synthesis in the mud crab, Scylla serrata.

Science.gov (United States)

Girish, B P; Swetha, C H; Reddy, P Sreenivasula

2017-09-02

In the current study, we have examined the role of serotonin in regulating the levels of methyl farnesoate and ecdysteroids in the giant mud crab Scylla serrata and validated that serotonin indeed is a reproductive hormone. Administration of serotonin elevated circulatory levels of methyl farnesoate and ecdysteroids in crabs. Since methyl farnesoate and ecdysteroid act through retinoid X receptor (RXR) and ecdysteroid receptor (EcR) respectively and these receptors are involved in the regulation of reproduction in crustaceans, we have determined the mRNA levels of RXR and EcR in hepatopancreas and ovary after serotonin administration. The expression levels of both RXR and EcR increased significantly in the hepatopancreas and ovary of serotonin injected crabs when compared to the controls. In vitro organ culture studies revealed that incubation of Y-orgas and mandibular organ explants in the presence of serotonin resulted in a significant increase in the secretion of ecdysteroids by Y-organs, but without alterations in MF synthesis in mandibular organs. From the above studies it is evident that serotonin stimulates Y organs resulting in increased ecdysteroidogenesis. Though the circulatory levels methyl farnesoate elevated after serotonin administration, organ culture studies revealed serotonin mediated methyl farnesaote synthesis is indirect probably by inhibiting release of mandibular organ inhibiting hormone from eyestalks. Copyright © 2017 Elsevier Inc. All rights reserved.

Prebiotic Amino Acid Thioester Synthesis: Thiol-Dependent Amino Acid Synthesis from Formose substrates (Formaldehyde and Glycolaldehyde) and Ammonia

Science.gov (United States)

Weber, Arthur L.

1998-01-01

Formaldehyde and glycolaldehyde (substrates of the formose autocatalytic cycle) were shown to react with ammonia yielding alanine and homoserine under mild aqueous conditions in the presence of thiol catalysts. Since similar reactions carried out without ammonia yielded alpha-hydroxy acid thioesters, the thiol-dependent synthesis of alanine and homoserine is presumed to occur via amino acid thioesters-intermediates capable of forming peptides. A pH 5.2 solution of 20 mM formaldehyde, 20 mM glycolaldehyde, 20 mM ammonium chloride, 23 mM 3-mercaptopropionic acid, and 23 mM acetic acid that reacted for 35 days at 40 C yielded (based on initial formaldehyde) 1.8% alanine and 0.08% homoserine. In the absence of thiol catalyst, the synthesis of alanine and homoserine was negligible. Alanine synthesis required both formaldehyde and glycolaldehyde, but homoserine synthesis required only glycolaldehyde. At 25 days the efficiency of alanine synthesis calculated from the ratio of alanine synthesized to formaldehyde reacted was 2.1%, and the yield (based on initial formaldehyde) of triose and tetrose intermediates involved in alanine and homoserine synthesis was 0.3 and 2.1%, respectively. Alanine synthesis was also seen in similar reactions containing only 10 mM each of aldehyde substrates, ammonia, and thiol. The prebiotic significance of these reactions that use the formose reaction to generate sugar intermediates that are converted to reactive amino acid thioesters is discussed.

Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

Science.gov (United States)

Steele, Andrew D; Keohane, Colleen E; Knouse, Kyle W; Rossiter, Sean E; Williams, Sierra J; Wuest, William M

2016-05-11

Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere.

Synthesis of nanoparticles and nanomaterials biological approaches

CERN Document Server