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Sample records for age-dependent protein carbonylation

  1. Age-related carbonyl stress and erythrocyte membrane protein carbonylation.

    PubMed

    Li, Guolin; Liu, Li; Hu, Hui; Zhao, Qiong; Xie, Fuxia; Chen, Keke; Liu, Shenglin; Chen, Yaqin; Shi, Wang; Yin, Dazhong

    2010-01-01

    Reactive carbonyl species (RCS) have been widely used as indicators of oxidative stress. However, the associations of carbonyl stress with aging process and biochemical alteration of erythrocyte are still poorly understood. Fresh blood samples in vacutainer tubes containing sodium heparinate were obtained from 874 volunteers who were divided into young, adult and old groups based on their age. Plasma RCS and thiols concentrations between different age groups and erythrocyte membrane protein carbonylation in the adult group were detected within 24h of the blood sampling. Results showed that the plasma thiols concentration decreased gradually during aging process, and the p-values between all three groups are less than 0.05. The plasma RCS concentration in different age groups showed a nonlinear association with age. The levels in the young group were slightly higher than the adult group (not significant) and lower than the old group (p < 0.01). The protein carbonylation of erythrocyte membrane was positively correlated with plasma RCS concentration (p < 0.01), but not plasma thiols concentration. We conclude that higher levels of RCS, not lower levels of thiols, in plasma are a direct risk factor for the protein carbonylation of erythrocyte membrane. Owing to the decrease of thiols levels and increase of RCS levels during aging process, a shift from RCS-related redox allostasis to carbonyl stress would contribute to age-related biological dysfunction and even aging process.

  2. Increased Adipose Protein Carbonylation in Human Obesity

    PubMed Central

    Frohnert, Brigitte I.; Sinaiko, Alan R.; Serrot, Federico J.; Foncea, Rocio E.; Moran, Antoinette; Ikramuddin, Sayeed; Choudry, Umar; Bernlohr, David A.

    2015-01-01

    Insulin resistance is associated with obesity but mechanisms controlling this relationship in humans are not fully understood. Studies in animal models suggest a linkage between adipose reactive oxygen species (ROS) and insulin resistance. ROS oxidize cellular lipids to produce a variety of lipid hydroperoxides that in turn generate reactive lipid aldehydes that covalently modify cellular proteins in a process termed carbonylation. Mammalian cells defend against reactive lipid aldehydes and protein carbonylation by glutathionylation using glutathione-S-transferase A4 (GSTA4) or carbonyl reduction/oxidation via reductases and/or dehydrogenases. Insulin resistance in mice is linked to ROS production and increased level of protein carbonylation, mitochondrial dysfunction, decreased insulin-stimulated glucose transport, and altered adipokine secretion. To assess protein carbonylation and insulin resistance in humans, eight healthy participants underwent subcutaneous fat biopsy from the periumbilical region for protein analysis and frequently sampled intravenous glucose tolerance testing to measure insulin sensitivity. Soluble proteins from adipose tissue were analyzed using two-dimensional gel electrophoresis and the major carbonylated proteins identified as the adipocyte and epithelial fatty acid–binding proteins. The level of protein carbonylation was directly correlated with adiposity and serum free fatty acids (FFAs). These results suggest that in human obesity oxidative stress is linked to protein carbonylation and such events may contribute to the development of insulin resistance. PMID:21593812

  3. Protein Carbonylation and Adipocyte Mitochondrial Function*

    PubMed Central

    Curtis, Jessica M.; Hahn, Wendy S.; Stone, Matthew D.; Inda, Jacob J.; Droullard, David J.; Kuzmicic, Jovan P.; Donoghue, Margaret A.; Long, Eric K.; Armien, Anibal G.; Lavandero, Sergio; Arriaga, Edgar; Griffin, Timothy J.; Bernlohr, David A.

    2012-01-01

    Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte. PMID:22822087

  4. A computational method to predict carbonylation sites in yeast proteins.

    PubMed

    Lv, H Q; Liu, J; Han, J Q; Zheng, J G; Liu, R L

    2016-01-01

    Several post-translational modifications (PTM) have been discussed in literature. Among a variety of oxidative stress-induced PTM, protein carbonylation is considered a biomarker of oxidative stress. Only certain proteins can be carbonylated because only four amino acid residues, namely lysine (K), arginine (R), threonine (T) and proline (P), are susceptible to carbonylation. The yeast proteome is an excellent model to explore oxidative stress, especially protein carbonylation. Current experimental approaches in identifying carbonylation sites are expensive, time-consuming and limited in their abilities to process proteins. Furthermore, there is no bioinformational method to predict carbonylation sites in yeast proteins. Therefore, we propose a computational method to predict yeast carbonylation sites. This method has total accuracies of 86.32, 85.89, 84.80, and 86.80% in predicting the carbonylation sites of K, R, T, and P, respectively. These results were confirmed by 10-fold cross-validation. The ability to identify carbonylation sites in different kinds of features was analyzed and the position-specific composition of the modification site-flanking residues was discussed. Additionally, a software tool has been developed to help with the calculations in this method. Datasets and the software are available at https://sourceforge.net/projects/hqlstudio/ files/CarSpred.Y/. PMID:27420944

  5. Protein carbonylation as a novel mechanism in redox signaling.

    PubMed

    Wong, Chi Ming; Cheema, Amrita K; Zhang, Lihua; Suzuki, Yuichiro J

    2008-02-15

    Reactive oxygen species serve as second messengers for signal transduction; however, molecular targets of oxidant signaling have not been defined. Here, we show that ligand-receptor-mediated signaling promotes reactive oxygen species-dependent protein carbonylation. Treatment of pulmonary artery smooth muscle cells with endothelin-1 increased protein carbonyls. Carbonylation of the majority of proteins occurred transiently, suggesting that there is also a mechanism for decarbonylation induced by endothelin-1. Decarbonylation was suppressed by inhibition of thioredoxin reductase, and cellular thioredoxin was upregulated during the decarbonylation phase. These results indicate that endothelin-1 promotes oxidant signaling as well as thioredoxin-mediated reductive signaling to regulate carbonylation and decarbonylation mechanisms. In cells treated with endothelin receptor antagonists, hydrogen peroxide scavengers, or an iron chelator, we identified, via mass spectrometry, proteins that are carbonylated in a receptor- and Fenton reaction-dependent manner, including annexin A1, which promotes apoptosis and suppresses cell growth. Carbonylation of annexin A1 by endothelin-1 was followed by proteasome-dependent degradation of this protein. We propose that carbonylation and subsequent degradation of annexin A1 may play a role in endothelin-mediated cell growth and survival, important events in pulmonary vascular remodeling. Protein carbonylation in response to ligand-receptor interactions represents a novel mechanism in redox signaling.

  6. Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cellular prion protein (PrPC) is a multifunctional protein, whose exact physiological role remains elusive. Since previous studies indicated a neuroprotective function of PrPC, we investigated whether Prnp knockout mice(Prnp0/0)display age-dependent behavioral abnormalities. Matched sets of Prnp0/0 ...

  7. Age-dependent expression of forkhead box O proteins in the duodenum of rats*

    PubMed Central

    Huang, Pan; Zhou, Zhen-qi; Huang, Rui-hua; Zhou, Bo; Wei, Quan-wei; Shi, Fang-xiong

    2011-01-01

    The O subfamily of forkhead box (FoxO) proteins is the downstream effector of the insulin-like growth factor-1/phosphoinositide 3-kinase/protein kinase B (IGF-1/PI3K/PKB) signal pathway. The objective of the present study was to examine the expressions of three members of FoxO proteins, FoxO1, FoxO3a, and FoxO4 in the duodenum of Sprague-Dawley rats at different ages. The result demonstrated that the expression of FoxO4 in rat duodenum showed an age-dependent manner. At Day 21, there were no detectable localization and expression of FoxO4 in the duodenum, while, at Months 2 and 6, localization and expression of FoxO4 were distinct. In addition, FoxO4 staining was primarily concentrated in the cell nuclei of the lamina propria around the intestinal gland of the duodenum in 2-month-old rats, but was not detectable in the same area in 6-month-old rats. Our results showed also that although FoxO3a existed in the cytoplasm of the lamina propria at a low level at the 2- and 6-month marks, it was still not detectable at Day 21. Besides, FoxO1 was not detectable in all parts and stages. Taken together, our findings suggested that the cell-specific and age-dependent expressional patterns of FoxO4 and FoxO3a proteins in the duodenum play some roles in the development and growth performance of the rat duodenum. PMID:21887848

  8. Determination of Protein Carbonylation and Proteasome Activity in Seeds.

    PubMed

    Xia, Qiong; El-Maarouf-Bouteau, Hayat; Bailly, Christophe; Meimoun, Patrice

    2016-01-01

    Reactive oxygen species (ROS) have been shown to be toxic but also function as signaling molecules in a process called redox signaling. In seeds, ROS are produced at different developmental stages including dormancy release and germination. Main targets of oxidation events by ROS in cell are lipids, nucleic acids, and proteins. Protein oxidation has various effects on their function, stability, location, and degradation. Carbonylation represents an irreversible and unrepairable modification that can lead to protein degradation through the action of the 20S proteasome. Here, we present techniques which allow the quantification of protein carbonyls in complex protein samples after derivatization by 2,4-dinitrophenylhydrazine (DNPH) and the determination proteasome activity by an activity-based protein profiling (ABPP) using the probe MV151. These techniques, routinely easy to handle, allow the rapid assessment of protein carbonyls and proteasome activity in seeds in various physiological conditions where ROS may act as signaling or toxic elements. PMID:27424756

  9. [Protein carbonylation and its role in physiological processes in plants].

    PubMed

    Debska, Karolina; Bogatek, Renata; Gniazdowska, Agnieszka

    2012-01-01

    Plant cells produce reactive oxygen species (ROS) continuously as a byproducts of oxygen metabolism and reaction to various environmental stresses. ROS are considered as chemicals inducing damage of cellular components (DNA, lipids and proteins), but also might act as signaling agents. Protein oxidation is one of covalent modification of protein induced by ROS or other products of oxidative stress. Carbonylation of particular amino acid residues (arginine, lysine, treonine or proline) is one of the most commonly occurring oxidative modification of proteins. This modification might lead to alteration in protein activity, its proteolytic breakdown or, in the opposite, aggregate formation. Carbonylated proteins have been identified in many plant species at different stage of growth and development. The analysis of subcellular localization of carbonylated proteins arised the hypothesis on their signaling function. We summarize the current knowledge on the detection of carbonylation protein in plants taking to the account the conditions which may influence their production or removal. We present also their putative role in plant physiology and discuss interaction between ROS and RNS in regulation of protein carbonylation. PMID:23214127

  10. Proteomic identification of age-dependent protein nitration in rat skeletal muscle.

    PubMed

    Kanski, Jaroslaw; Alterman, Michail A; Schöneich, Christian

    2003-11-15

    Age-related protein nitration was studied in skeletal muscle of Fisher 344 and Fisher 344/Brown Norway (BN) F1 rats by a proteomic approach. Proteins from young (4 months) and old (24 months) Fisher 344 rats and young (6 months) and old (34 months) Fisher 344/BN F1 animals were separated by 2-D gel electrophoresis. Western blot showed an age-related increase in the nitration of a few specific proteins, which were identified by MALDI-TOF MS and ESI-MS/MS. We identified age-dependent apparent nitration of beta-enolase, alpha-fructose aldolase, and creatine kinase, which perform important functions in muscle energy metabolism, suggesting that the nitration of such key proteins can be, in part, responsible for the decline of muscle motor function of the muscle. Furthermore, we have identified the apparent nitration of succinate dehydrogenase, rab GDP dissociation inhibitor beta (GdI-2), triosephosphate isomerase, troponin I, alpha-crystallin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

  11. Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression.

    PubMed

    Schmitz, Matthias; Greis, Catharina; Ottis, Philipp; Silva, Christopher J; Schulz-Schaeffer, Walter J; Wrede, Arne; Koppe, Katharina; Onisko, Bruce; Requena, Jesús R; Govindarajan, Nambirajan; Korth, Carsten; Fischer, Andre; Zerr, Inga

    2014-12-01

    The cellular prion protein (PrPC) is a highly conserved protein whose exact physiological role remains elusive. In the present study, we investigated age-dependent behavioral abnormalities in PrPC-knockout (Prnp0/0) mice and wild-type (WT) controls. Prnp0/0 mice showed age-dependent behavioral deficits in memory performance, associative learning, basal anxiety, and nest building behavior. Using a hypothesis-free quantitative proteomic investigation, we found that loss of PrPC affected the levels of neurofilament proteins in an age-dependent manner. In order to understand the biochemical basis of these observations, we analyzed the phosphorylation status of neurofilament heavy chain (NF-H). We found a reduction in NF-H phosphorylation in both Prnp0/0 mice and in PrPC-deficient cells. The expression of Fyn and phospho-Fyn, a potential regulator for NF phosphorylation, was associated with PrPC ablation. The number of β-tubulin III-positive neurons in the hippocampus was diminished in Prnp0/0 mice relative to WT mice. These data indicate that PrPC plays an important role in cytoskeletal organization, brain function, and age-related neuroprotection. Our work represents the first direct biochemical link between these proteins and the observed behavioral phenotypes.

  12. Exploring the biology of lipid peroxidation-derived protein carbonylation.

    PubMed

    Fritz, Kristofer S; Petersen, Dennis R

    2011-09-19

    The sustained overproduction of reactive oxygen and nitrogen species results in an imbalance of cellular prooxidant-antioxidant systems and is implicated in numerous disease states, including alcoholic liver disease, cancer, neurological disorders, inflammation, and cardiovascular disease. The accumulation of reactive aldehydes resulting from sustained oxidative stress and lipid peroxidation is an underlying factor in the development of these pathologies. Determining the biochemical factors that elicit cellular responses resulting from protein carbonylation remains a key element to developing therapeutic approaches and ameliorating disease pathologies. This review details our current understanding of the generation of reactive aldehydes via lipid peroxidation resulting in protein carbonylation, focusing on pathophysiologic factors associated with 4-hydroxynonenal-protein modification. Additionally, an overview of in vitro and in vivo model systems used to study the physiologic impact of protein carbonylation is presented. Finally, an update of the methods commonly used in characterizing protein modification by reactive aldehydes provides an overview of isolation techniques, mass spectrometry, and computational biology. It is apparent that research in this area employing state-of-the-art proteomics, mass spectrometry, and computational biology is rapidly evolving, yielding foundational knowledge concerning the molecular mechanisms of protein carbonylation and its relation to a spectrum of diseases associated with oxidative stress. PMID:21812433

  13. Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

    NASA Astrophysics Data System (ADS)

    Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

    2016-01-01

    Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis.

  14. Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

    PubMed Central

    Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

    2016-01-01

    Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis. PMID:26776680

  15. Plasma protein carbonyl levels and breast cancer risk.

    PubMed

    Rossner, Pavel; Terry, Mary Beth; Gammon, Marilie D; Agrawal, Meenakshi; Zhang, Fang Fang; Ferris, Jennifer S; Teitelbaum, Susan L; Eng, Sybil M; Gaudet, Mia M; Neugut, Alfred I; Santella, Regina M

    2007-01-01

    To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9-1.5; OR = 1.5, 95% CI = 1.2-2.0; OR = 1.6, 95% CI = 1.2-2.1, for the 2(nd), 3(rd) and 4(th) quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (<50 years) and older women, more pronounced among women with higher physical activity levels (0.7 hrs/week for 4(th) quartile versus lowest quartile OR = 2.0, 95% CI = 1.4-3.0), higher alcohol consumption (> or = 15 grams/day for 4(th) quartile versus lowest quartile OR = 2.3, 95% CI = 1.1-4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6-4.4 for 4(th) quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F(2t)-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2-2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.

  16. [Carbonyl stress and oxidatively modified proteins in chronic renal failure].

    PubMed

    Bargnoux, A-S; Morena, M; Badiou, S; Dupuy, A-M; Canaud, B; Cristol, J-P

    2009-01-01

    Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis. PMID:19297289

  17. Age-related variations of protein carbonyls in human saliva and plasma: is saliva protein carbonyls an alternative biomarker of aging?

    PubMed

    Wang, Zhihui; Wang, Yanyi; Liu, Hongchen; Che, Yuwei; Xu, Yingying; E, Lingling

    2015-06-01

    Free radical hypothesis which is one of the most acknowledged aging theories was developed into oxidative stress hypothesis. Protein carbonylation is by far one of the most widely used markers of protein oxidation. We studied the role of age and gender in protein carbonyl content of saliva and plasma among 273 Chinese healthy subjects (137 females and 136 males aged between 20 and 79) and discussed the correlation between protein carbonyl content of saliva and plasma. Protein carbonyl content of saliva and plasma were, respectively, 2.391 ± 0.639 and 0.838 ± 0.274 nmol/mg. Variations of saliva and plasma different age groups all reached significant differences in both male and female (all p < 0.05) while both saliva and plasma protein carbonyls were found to be significantly correlated with age (r = 0.6582 and r = 0.5176, all p < 0.001). Gender was discovered to be unrelated to saliva and plasma protein carbonyl levels (all p > 0.05). Saliva and plasma protein carbonyls were positively related (r = 0.4405, p < 0.001). Surprisingly, saliva and plasma protein carbonyls/ferric reducing ability of plasma (FRAP) ratios were proved to be significantly correlated with age (r = 0.7796 and r = 0.6938, all p < 0.001) while saliva protein carbonyls/FRAP ratio and plasma protein carbonyls/FRAP ratio were also correlated (r = 0.5573, p < 0.001). We concluded that saliva protein carbonyls seem to be an alternative biomarker of aging while the mechanisms of protein carbonylation and oxidative stress and the relationship between saliva protein carbonyls and diseases need to be further investigated.

  18. Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective.

    PubMed

    Møller, Ian M; Rogowska-Wrzesinska, Adelina; Rao, R S P

    2011-10-19

    Proteins can become oxidatively modified in many different ways, either by direct oxidation of amino acid side chains and protein backbone or indirectly by conjugation with oxidation products of polyunsaturated fatty acids and carbohydrates. While reversible oxidative modifications are thought to be relevant in physiological processes, irreversible oxidative modifications are known to contribute to cellular damage and disease. The most well-studied irreversible protein oxidation is carbonylation. In this work we first examine how protein carbonylation occurs via metal-catalyzed oxidation (MCO) in vivo and in vitro with an emphasis on cellular metal ion homeostasis and metal binding. We then review proteomic methods currently used for identifying carbonylated proteins and their sites of modification. Finally, we discuss the identified carbonylated proteins and the pattern of carbonylation sites in relation to cellular metabolism using the mitochondrion as a case story.

  19. Protein carbonylation, protein aggregation and neuronal cell death in a murine model of multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Dasgupta, Anushka

    Many studies have suggested that oxidative stress plays an important role in the pathophysiology of both multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Yet, the mechanism by which oxidative stress leads to tissue damage in these disorders is unclear. Recent work from our laboratory has revealed that protein carbonylation, a major oxidative modification caused by severe and/or chronic oxidative stress conditions, is elevated in MS and EAE. Furthermore, protein carbonylation has been shown to alter protein structure leading to misfolding/aggregation. These findings prompted me to hypothesize that carbonylated proteins, formed as a consequence of oxidative stress and/or decreased proteasomal activity, promote protein aggregation to mediate neuronal apoptosis in vitro and in EAE. To test this novel hypothesis, I first characterized protein carbonylation, protein aggregation and apoptosis along the spinal cord during the course of myelin-oligodendrocyte glycoprotein (MOG)35-55 peptide-induced EAE in C57BL/6 mice [Chapter 2]. The results show that carbonylated proteins accumulate throughout the course of the disease, albeit by different mechanisms: increased oxidative stress in acute EAE and decreased proteasomal activity in chronic EAE. I discovered not only that there is a temporal correlation between protein carbonylation and apoptosis but also that carbonyl levels are significantly higher in apoptotic cells. A high number of juxta-nuclear and cytoplasmic protein aggregates containing the majority of the oxidized proteins are also present during the course of EAE, which seems to be due to reduced autophagy. In chapter 3, I show that when gluthathione levels are reduced to those in EAE spinal cord, both neuron-like PC12 (nPC12) cells and primary neuronal cultures accumulate carbonylated proteins and undergo cell death (both by necrosis and apoptosis). Immunocytochemical and biochemical studies also revealed a temporal

  20. Two-dimensional gel electrophoretic detection of protein carbonyls derivatized with biotin-hydrazide.

    PubMed

    Wu, Jinzi; Luo, Xiaoting; Jing, Siqun; Yan, Liang-Jun

    2016-04-15

    Protein carbonyls are protein oxidation products that are often used to measure the magnitude of protein oxidative damage induced by reactive oxygen or reactive nitrogen species. Protein carbonyls have been found to be elevated during aging and in age-related diseases such as stroke, diabetes, and neurodegenerative diseases. In the present article, we provide detailed protocols for detection of mitochondrial protein carbonyls labeled with biotin-hydrazide followed by 2-dimensional isoelectric focusing (IEF)/SDS-PAGE and Western blotting probed with horse-radish peroxidase-conjugated streptavidin. The presented procedures can also be modified for detection of carbonylation of non-mitochondrial proteins. PMID:26590475

  1. Proteomic identification of carbonylated proteins in the kidney of trichloroethene-exposed MRL+/+ mice

    PubMed Central

    Fan, Xiuzhen; Wang, Gangduo; English, Robert D.; Khan, M. Firoze

    2013-01-01

    Trichloroethene (TCE), a common environmental and occupational pollutant, is associated with multi-organ toxicity. Kidney is one of major target organs affected as a result of TCE exposure. Our previous studies have shown that exposure to TCE causes increased protein oxidation (protein carbonylation) in the kidneys of autoimmune-prone MRL +/+ mice, and suggested a potential role of protein oxidation in TCE-mediated nephrotoxicity. To assess the impact of chronic TCE exposure on protein oxidation, particularly to identify the carbonylated proteins in kidneys, female MRL+/+ mice were treated with TCE at the dose of 2 mg/ml via drinking water for 36 weeks and kidney protein extracts were analyzed for protein carbonyls and carbonylated proteins identified using proteomic approaches (2D gel, Western blot, MALDI TOF/TOF MS/MS, etc.). TCE treatment led to significantly increased protein carbonyls in the kidney protein extracts (20,000g pellet fraction). Interestingly, among 18 identified carbonylated proteins, 10 were found only in the kidneys of TCE-treated mice, whereas other 8 were present in the kidneys of both control and TCE-treated mice. The identified carbonylated proteins represent skeletal proteins, chaperones, stress proteins, enzymes, plasma protein, and proteins involved in signaling pathways. The findings provide a map for further exploring the role of carbonylated proteins in TCE-mediated nephrotoxicity. PMID:24024666

  2. Age-dependent degradation of the protein adsorption capacity of titanium.

    PubMed

    Hori, N; Att, W; Ueno, T; Sato, N; Yamada, M; Saruwatari, L; Suzuki, T; Ogawa, T

    2009-07-01

    Reported bone-implant contact percentages are far below the ideal 100%. We tested a hypothesis that the protein adsorption capability of titanium, which is critical to the process of osseointegration, changes over time before its use. Machined, acid-etched, and sandblasted surfaces were prepared and stored under dark ambient conditions for 3 days, 1 week, or 4 weeks. For all surfaces, protein adsorption decreased as the storage time increased, and their decreasing rates were dependent on titanium topography. After 4 weeks, the amounts of albumin and fibronectin adsorbed by the acid-etched surface were only 20% and 35%, respectively, of that adsorbed by the fresh surface after 2 hours of incubation, and remained substantially low even after 24 hours. This time-dependent degradation in protein adsorption of titanium correlated with its naturally decreasing hydrophilicity, which was not observed for the nickel and chromium surfaces, indicating a titanium-specific biological aging.

  3. Age-dependent decline of nogo-a protein in the mouse cerebrum.

    PubMed

    Kumari, Anita; Thakur, M K

    2014-11-01

    Nogo-A, a myelin-associated neurite growth inhibitory protein, is implicated in synaptic plasticity. It binds to its receptor namely the Nogo-66 receptor1 (NgR1) and regulates filamentous (F) actin dynamics via small GTPases of the Rho family, RhoA kinase (ROCK), LimK and cofilin. These proteins are associated with the structural plasticity, one of the components of synaptic plasticity, which is known to decline with normal aging. So, the level of Nogo-A and its receptor NgR1 are likely to vary during normal brain aging. However, it is not clearly understood how the levels of Nogo-A and its receptor NgR1 change in the cerebrum during aging. Several studies show an age- and gender-dependent decline in synaptic plasticity. Therefore, the present study was planned to analyze the relative changes in the mRNA and protein levels of Nogo-A and NgR1 in both male and female mice cerebrum during normal aging. Western blot analysis has shown decrease in Nogo-A protein level during aging in both male and female mice cerebrum. This was further confirmed by immunofluorescence analysis. RT-PCR analysis of Nogo-A mRNA showed no significant difference in the above-mentioned groups. This was also supported by in situ hybridization. NgR1 protein and its mRNA expression levels showed no significant alteration with aging in the cerebrum of both male and female mice. Taken together, we speculate that the downregulation of Nogo-A protein might have a role in the altered synaptic plasticity during aging.

  4. Age-dependent changes in extracellular proteins, aminopeptidase and proteinase activities in Frankia isolate BR.

    PubMed

    Müller, A; Benoist, P; Diem, H G; Schwencke, J

    1991-12-01

    To investigate protein secretion by the nitrogen-fixing actinomycete Frankia isolate BR, we designed a rapid DEAE adsorption, salt elution and Biogel P6DG desalination method to concentrate protein from the growth medium. Secreted proteins reached a maximum concentration (5.6 gm l-1) in the medium at growth arrest. Analysis by SDS-PAGE detected up to 63 extracellular polypeptides when Frankia cells were grown under stirred conditions in BAP medium supplemented with phosphatidylcholine and MES buffer and 65 proteins in stirred BAP media alone. The pattern of extracellular polypeptides changed during growth. Several extracellular proteolytic activities were detected and compared with intracellular ones. The substrate specificity of the extracellular and intracellular aminopeptidase activities were the same. Also, the electrophoretic migration patterns of secreted and intracellular aminopeptidases could not be distinguished. Secretion of the proline-specific aminopeptidase FAP proteinase (PF) were secreted: 10 had the same electrophoretic mobility as their intracellular counterparts after SDS-gelatine-PAGE while five (PF - 39.5, PF - 38.5, PF - 36.5, PF - 25.5 and PF - 20.5 kDa) had a different electrophoretic mobility and, therefore, appeared to be exclusively extracellular. At least seven extracellular proteinases appeared to increase coordinately in activity shortly before growth arrest.

  5. Age-dependent increase in the expression of antioxidant-like protein-1 in the gerbil hippocampus

    PubMed Central

    Park, Jin-A; Park, Joon Ha; Ahn, Ji Hyeon; Kim, Jong-Dai; Won, Moo-Ho; Lee, Choong-Hyun

    2016-01-01

    Antioxidant-like protein-1 (AOP-1) reduces the intracellular level of reactive oxygen species. In the present study, the age-related change in AOP-1 expression in the hippocampus among young, adult and aged gerbils was compared using western blot analysis and immunohistochemistry. The results demonstrated that the protein expression of AOP-1 was gradually and significantly increased in the hippocampus during the normal aging process. In addition, the age-dependent increase in AOP-1 immunoreactivity was also observed in pyramidal neurons of the hippocampus proper; however, in the dentate gyrus, AOP-1 immunoreactivity was not altered during the normal aging process. These results indicated that the expression of AOP-1 is significantly increased in the hippocampus proper, but not in the dentate gyrus, during the normal aging process. PMID:27511601

  6. Age-Dependent Impairment of Eyeblink Conditioning in Prion Protein-Deficient Mice

    PubMed Central

    Kishimoto, Yasushi; Hirono, Moritoshi; Atarashi, Ryuichiro; Sakaguchi, Suehiro; Yoshioka, Tohru; Katamine, Shigeru; Kirino, Yutaka

    2013-01-01

    Mice lacking the prion protein (PrPC) gene (Prnp), Ngsk Prnp0/0 mice, show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Because PrPC is highly expressed in cerebellar neurons (including PCs and granule cells), it may be involved in cerebellar synaptic function and cerebellar cognitive function. However, no studies have been conducted to investigate the possible involvement of PrPC and/or PrPLP/Dpl in cerebellum-dependent discrete motor learning. Therefore, the present cross-sectional study was designed to examine cerebellum-dependent delay eyeblink conditioning in Ngsk Prnp0/0 mice in adulthood (16, 40, and 60 weeks of age). The aims of the present study were two-fold: (1) to examine the role of PrPC and/or PrPLP/Dpl in cerebellum-dependent motor learning and (2) to confirm the age-related deterioration of eyeblink conditioning in Ngsk Prnp0/0 mice as an animal model of progressive cerebellar degeneration. Ngsk Prnp0/0 mice aged 16 weeks exhibited intact acquisition of conditioned eyeblink responses (CRs), although the CR timing was altered. The same result was observed in another line of PrPc-deficient mice, ZrchI PrnP0/0 mice. However, at 40 weeks of age, CR incidence impairment was observed in Ngsk Prnp0/0 mice. Furthermore, Ngsk Prnp0/0 mice aged 60 weeks showed more significantly impaired CR acquisition than Ngsk Prnp0/0 mice aged 40 weeks, indicating the temporal correlation between cerebellar PC degeneration and motor learning deficits. Our findings indicate the importance of the cerebellar cortex in delay eyeblink conditioning and suggest an important physiological role of prion protein in cerebellar motor learning. PMID:23593266

  7. Evaluating the Age-Dependent Potential for Protein Deposition in Naked Neck Meat Type Chicken

    PubMed Central

    Khan, Daulat R.; Wecke, Christian; Sharifi, Ahmad R.; Liebert, Frank

    2015-01-01

    Simple Summary Growth rates of fast-growing chickens are reduced by a higher ambient temperature (AT) because of difficulties in dissipating heat through the feather coverage. Naked neck meat type genotypes could be helpful in increasing the tolerance for high AT. However, basic model parameters of this genotype necessary to further assess amino acid requirements are as yet unavailable. The experiments were conducted to estimate both the daily nitrogen maintenance requirement (NMR) and the potential for daily nitrogen retention NRmaxT). These observed model parameters provide the basic information to characterize the growth potential of the genotype for further application in modeling of individual amino acid requirements of naked neck meat type chicken. Abstract The introduction of the naked neck gene (Na) into modern meat type chicken is known to be helpful in increasing the tolerance for a high ambient temperature (AT) by reducing the feather coverage which allows for a higher level of heat dissipation compared to normally feathered (na/na) birds. In addition, reduced feather coverage could affect requirements for sulfur containing amino acids. As a prerequisite for further modeling of individual amino acid requirements, the daily N maintenance requirement (NMR) and the threshold value of daily N retention (NRmaxT) were determined. This was carried out using graded dietary protein supply and exponential modeling between N intake (NI) and N excretion (NEX) or N deposition (ND), respectively. Studies with homozygous (Na/Na) and heterozygous (Na/na) naked neck meat type chicken utilized 144 birds of average weight (50% of each genotype and sex) within two N balance experiments during both the starter (days 10–20) and the grower period (days 25–35). Birds were randomly allotted to five diets with graded dietary protein supply but constant protein quality. The observed estimates depending on genotype, sex and age varied for NMR and NRmaxT from 224 to 395 and 2881

  8. Oxidative stress induces age-dependent changes in lymphocyte protein synthesis and second messenger levels.

    PubMed

    Lopez-Hellin, J; Garcia-Arumi, E; Schwartz, S

    1998-01-01

    Cumulative damage in cells from aged people could lead to a greater fragility against acute oxidative stress. The effects of acute oxidative stress on cell viability, cAMP and cGMP concentrations, and protein synthesis rates were studied in lymphocytes from 25 young and 26 elderly subjects. Lymphocytes were exposed to stress by hydrogen peroxide 25 micromol/l and incubated for 18 hours. Cell viability after stress was lower (p<0.0001, Student's t test) in cells from the elderly (63.4%) than in cells from the young donors (73.2%). The protein synthesis rate was also lower after stress (p<0.04, Mann-Whitney U test) in cells from the elderly (47.3% vs. non-stressed cells), than in cells from the young (82.19% vs. non-stressed cells). After oxidative stress, cAMP and cGMP concentrations showed no significant changes in cells from young subjects; there were, however, significant decreases in these cyclic nucleotides in cells from the elderly (p<0.008 for both nucleotides, paired Student's t test). There were no differences in basal cAMP or cGMP levels between the two groups. These results show that mortality and metabolic changes due to oxidative stress are greater in lymphocytes proceeding from elderly subjects than in those from young subjects.

  9. Proteomic identification of mitochondrial carbonylated proteins in two maturation stages of pepper fruits.

    PubMed

    Camejo, Daymi; Jiménez, Ana; Palma, José M; Sevilla, Francisca

    2015-08-01

    Pepper fruits in green and red maturation stages were selected to study the protein pattern modified by oxidation measuring carbonylated proteins in isolated mitochondria, together with the accumulation of superoxide radical and hydrogen peroxide in the fruits. MALDI-TOF/TOF analysis identified as carbonylated proteins in both green and red fruits, formate dehydrogenase, NAD-dependent isocitrate dehydrogenase, porin, and defensin, pointing to a common regulation by carbonylation of these proteins independently of the maturation stage. However, other proteins such as glycine dehydrogenase P subunit and phosphate transporter were identified as targets of carbonylation only in green fruits, whereas aconitase, ATPase β subunit, prohibitin, orfB protein, and cytochrome C oxidase, were identified only in red fruits. In general, the results suggest that carbonylation of mitochondrial proteins is a PTM that drives the complex ripening process, probably establishing the accumulation and functionality of some mitochondrial proteins in the nonclimacteric pepper fruit.

  10. Targeting Heat Shock Proteins Mitigates Ventilator Induced Diaphragm Muscle Dysfunction in an Age-Dependent Manner

    PubMed Central

    Ogilvie, Hannah; Cacciani, Nicola; Akkad, Hazem; Larsson, Lars

    2016-01-01

    Intensive care unit (ICU) patients are often overtly subjected to mechanical ventilation and immobilization, which leads to impaired limb and respiratory muscle function. The latter, termed ventilator-induced diaphragm dysfunction (VIDD) has recently been related to compromised heat shock protein (Hsp) activation. The administration of a pharmacological drug BGP-15 acting as a Hsp chaperone co-inducer has been found to partially alleviate VIDD in young rats. Considering that the mean age in the ICU is increasing, we aimed to explore whether the beneficial functional effects are also present in old rats. For that, we exposed young (7–8 months) and old (28–32 months) rats to 5-day controlled mechanical ventilation and immobilization with or without systemic BGP-15 administration. We then dissected diaphragm muscles, membrane–permeabilized bundles and evaluated the contractile function at single fiber level. Results confirmed that administration of BGP-15 restored the force-generating capacity of isolated muscle cells from young rats in conjunction with an increased expression of Hsp72. On the other hand, our results highlighted that old rats did not positively respond to the BGP-15 treatment. Therefore, it is of crucial importance to comprehend in more depth the effect of VIDD on diaphragm function and ascertain any further age-related differences. PMID:27729867

  11. A step-by-step protocol for assaying protein carbonylation in biological samples.

    PubMed

    Colombo, Graziano; Clerici, Marco; Garavaglia, Maria Elisa; Giustarini, Daniela; Rossi, Ranieri; Milzani, Aldo; Dalle-Donne, Isabella

    2016-04-15

    Protein carbonylation represents the most frequent and usually irreversible oxidative modification affecting proteins. This modification is chemically stable and this feature is particularly important for storage and detection of carbonylated proteins. Many biochemical and analytical methods have been developed during the last thirty years to assay protein carbonylation. The most successful method consists on protein carbonyl (PCO) derivatization with 2,4-dinitrophenylhydrazine (DNPH) and consequent spectrophotometric assay. This assay allows a global quantification of PCO content due to the ability of DNPH to react with carbonyl giving rise to an adduct able to absorb at 366 nm. Similar approaches were also developed employing chromatographic separation, in particular HPLC, and parallel detection of absorbing adducts. Subsequently, immunological techniques, such as Western immunoblot or ELISA, have been developed leading to an increase of sensitivity in protein carbonylation detection. Currently, they are widely employed to evaluate change in total protein carbonylation and eventually to highlight the specific proteins undergoing selective oxidation. In the last decade, many mass spectrometry (MS) approaches have been developed for the identification of the carbonylated proteins and the relative amino acid residues modified to carbonyl derivatives. Although these MS methods are much more focused and detailed due to their ability to identify the amino acid residues undergoing carbonylation, they still require too expensive equipments and, therefore, are limited in distribution. In this protocol paper, we summarise and comment on the most diffuse protocols that a standard laboratory can employ to assess protein carbonylation; in particular, we describe step-by-step the different protocols, adding suggestions coming from our on-bench experience.

  12. Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences.

    PubMed

    Lazarus, Rachel C; Buonora, John E; Jacobowitz, David M; Mueller, Gregory P

    2015-01-01

    Protein carbonylation is a well-documented and quantifiable consequence of oxidative stress in several neuropathologies, including multiple sclerosis, Alzheimer׳s disease, and Parkinson׳s disease. Although oxidative stress is a hallmark of traumatic brain injury (TBI), little work has explored the specific neural regions and cell types in which protein carbonylation occurs. Furthermore, the effect of gender on protein carbonylation after TBI has not been studied. The present investigation was designed to determine the regional and cell specificity of TBI-induced protein carbonylation and how this response to injury is affected by gender. Immunohistochemistry was used to visualize protein carbonylation in the brains of adult male and female Sprague-Dawley rats subjected to controlled cortical impact (CCI) as an injury model of TBI. Cell-specific markers were used to colocalize the presence of carbonylated proteins in specific cell types, including astrocytes, neurons, microglia, and oligodendrocytes. Results also indicated that the injury lesion site, ventral portion of the dorsal third ventricle, and ventricular lining above the median eminence showed dramatic increases in protein carbonylation after injury. Specifically, astrocytes and limited regions of ependymal cells adjacent to the dorsal third ventricle and the median eminence were most susceptible to postinjury protein carbonylation. However, these patterns of differential susceptibility to protein carbonylation were gender dependent, with males showing significantly greater protein carbonylation at sites distant from the lesion. Proteomic analyses were also conducted and determined that the proteins most affected by carbonylation in response to TBI include glial fibrillary acidic protein, dihydropyrimidase-related protein 2, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A. Many other proteins, however, were not carbonylated by CCI. These findings indicate that there is both regional

  13. Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences.

    PubMed

    Lazarus, Rachel C; Buonora, John E; Jacobowitz, David M; Mueller, Gregory P

    2015-01-01

    Protein carbonylation is a well-documented and quantifiable consequence of oxidative stress in several neuropathologies, including multiple sclerosis, Alzheimer׳s disease, and Parkinson׳s disease. Although oxidative stress is a hallmark of traumatic brain injury (TBI), little work has explored the specific neural regions and cell types in which protein carbonylation occurs. Furthermore, the effect of gender on protein carbonylation after TBI has not been studied. The present investigation was designed to determine the regional and cell specificity of TBI-induced protein carbonylation and how this response to injury is affected by gender. Immunohistochemistry was used to visualize protein carbonylation in the brains of adult male and female Sprague-Dawley rats subjected to controlled cortical impact (CCI) as an injury model of TBI. Cell-specific markers were used to colocalize the presence of carbonylated proteins in specific cell types, including astrocytes, neurons, microglia, and oligodendrocytes. Results also indicated that the injury lesion site, ventral portion of the dorsal third ventricle, and ventricular lining above the median eminence showed dramatic increases in protein carbonylation after injury. Specifically, astrocytes and limited regions of ependymal cells adjacent to the dorsal third ventricle and the median eminence were most susceptible to postinjury protein carbonylation. However, these patterns of differential susceptibility to protein carbonylation were gender dependent, with males showing significantly greater protein carbonylation at sites distant from the lesion. Proteomic analyses were also conducted and determined that the proteins most affected by carbonylation in response to TBI include glial fibrillary acidic protein, dihydropyrimidase-related protein 2, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A. Many other proteins, however, were not carbonylated by CCI. These findings indicate that there is both regional

  14. Effect of protein diet on age-dependent methylation of liver nuclear components of mice administered N-nitrosodimethylamine

    SciTech Connect

    Klaude, M.; von der Decken, A.

    1984-10-01

    Protein diets deficient or enriched in DL-methionine were studied for the effect of methylation of nuclear components in subadult and adult outbred albino male mice given N-nitrosodimethylamine. After the mice were fed diets for 6 days, they were given ip injections of (/sup 14/C)N-nitrosodimethylamine (5 mg/kg body wt) and killed 45 minutes later. Liver nuclei were isolated; incorporation of /sup 14/C into nuclear proteins and methylation of DNA and RNA were determined. In the subadult and adult animals the nuclear protein content was diminished by shortage of a single essential amino acid. Incorporation of /sup 14/C into the total protein was reduced. The reduction amounted to 55% in the subadult and 23% in the adult animals. Neither an age-dependent nor a diet-dependent change in the specific methylation of DNA and RNA was observed. Analysis of methylation of DNA and RNA was observed. Analysis of methylated purine bases showed an age-related rise in O6-methylguanine in the adult as compared with the subadult mice.

  15. Protein carbonylation and heat shock proteins in human skeletal muscle: relationships to age and sarcopenia.

    PubMed

    Beltran Valls, Maria R; Wilkinson, Daniel J; Narici, Marco V; Smith, Kenneth; Phillips, Bethan E; Caporossi, Daniela; Atherton, Philip J

    2015-02-01

    Aging is associated with a gradual loss of muscle mass termed sarcopenia, which has significant impact on quality-of-life. Because oxidative stress is proposed to negatively impact upon musculoskeletal aging, we investigated links between human aging and markers of oxidative stress, and relationships to muscle mass and strength in young and old nonsarcopenic and sarcopenic adults. Sixteen young and 16 old males (further subdivided into "old" and "old sarcopenic") were studied. The abundance of protein carbonyl adducts within skeletal muscle sarcoplasmic, myofibrillar, and mitochondrial protein subfractions from musculus vastus lateralis biopsies were determined using Oxyblot immunoblotting techniques. In addition, concentrations of recognized cytoprotective proteins (eg, heat shock proteins [HSP], αβ-crystallin) were also assayed. Aging was associated with increased mitochondrial (but not myofibrillar or sarcoplasmic) protein carbonyl adducts, independently of (stage-I) sarcopenia. Correlation analyses of all subjects revealed that mitochondrial protein carbonyl abundance negatively correlated with muscle strength ([1-repetition maximum], p = .02, r (2) = -.16), but not muscle mass (p = .13, r (2) = -.08). Abundance of cytoprotective proteins, including various HSPs (HSP 27 and 70), were unaffected by aging/sarcopenia. To conclude, these data reveal that mitochondrial protein carbonylation increases moderately with age, and that this increase may impact upon skeletal muscle function, but is not a hallmark of (stage-I) sarcopenia, per se.

  16. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana.

    PubMed

    Saur, Isabel M L; Kadota, Yasuhiro; Sklenar, Jan; Holton, Nicholas J; Smakowska, Elwira; Belkhadir, Youssef; Zipfel, Cyril; Rathjen, John P

    2016-03-22

    Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined.

  17. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana

    PubMed Central

    Saur, Isabel M. L.; Kadota, Yasuhiro; Sklenar, Jan; Holton, Nicholas J.; Smakowska, Elwira; Belkhadir, Youssef; Zipfel, Cyril; Rathjen, John P.

    2016-01-01

    Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined. PMID:26944079

  18. NbCSPR underlies age-dependent immune responses to bacterial cold shock protein in Nicotiana benthamiana.

    PubMed

    Saur, Isabel M L; Kadota, Yasuhiro; Sklenar, Jan; Holton, Nicholas J; Smakowska, Elwira; Belkhadir, Youssef; Zipfel, Cyril; Rathjen, John P

    2016-03-22

    Plants use receptor kinases (RKs) and receptor-like proteins (RLPs) as pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) that are typical of whole classes of microbes. After ligand perception, many leucine-rich repeat (LRR)-containing PRRs interact with the LRR-RK BRI1-ASSOCIATED KINASE 1 (BAK1). BAK1 is thus expected to interact with unknown PRRs. Here, we used BAK1 as molecular bait to identify a previously unknown LRR-RLP required for the recognition of the csp22 peptide derived from bacterial cold shock protein. We established a method to identify proteins that interact with BAK1 only after csp22 treatment. BAK1 was expressed transiently in Nicotiana benthamiana and immunopurified after treatment with csp22. BAK1-associated proteins were identified by mass spectrometry. We identified several proteins including known BAK1 interactors and a previously uncharacterized LRR-RLP that we termed RECEPTOR-LIKE PROTEIN REQUIRED FOR CSP22 RESPONSIVENESS (NbCSPR). This RLP associates with BAK1 upon csp22 treatment, and NbCSPR-silenced plants are impaired in csp22-induced defense responses. NbCSPR confers resistance to bacteria in an age-dependent and flagellin-induced manner. As such, it limits bacterial growth and Agrobacterium-mediated transformation of flowering N. benthamiana plants. Transgenic expression of NbCSPR into Arabidopsis thaliana conferred responsiveness to csp22 and antibacterial resistance. Our method may be used to identify LRR-type RKs and RLPs required for PAMP perception/responsiveness, even when the active purified PAMP has not been defined. PMID:26944079

  19. Blot-MS of Carbonylated Proteins: A Tool to Identify Oxidized Proteins.

    PubMed

    Ferreira, Rita; Domingues, Pedro; Amado, Francisco; Vitorino, Rui

    2016-01-01

    The efficiency of proteostasis regulation declines during aging and the failure of protein homeostasis is common in age-related diseases. Protein oxidation is a major contributor to the loss of proteome homeostasis, also called "proteostasis," precluding protein misfolding and aggregation. So, the identification of the molecular pathways impaired by protein oxidation will increase the understanding of proteostasis and the pathophysiological conditions related to the loss of proteostasis. Sample derivatization with dinitrophenyl hydrazine and western blot immunoassay detection of carbonylated proteins (commonly known as Oxyblot™) coupled to mass spectrometry (blot-MS) is an attractive methodological approach to identify proteins that are more prone to carbonylation, a typical oxidative modification of amino acid residues. The integration of blot-MS data of carbonylated proteins with bioinformatics tools allows the identification of the biological processes more affected by protein oxidation and that, eventually, result in the loss of proteostasis.In this chapter, we describe a blot-MS methodology to identify the proteins more prone to oxidation in biological samples, as cell and tissue extracts, and biofluids. Analysis of mitochondria isolated from cardiac tissue is provided as an example. Bioinformatic strategy to deal with data retrieved from blot-MS experiments are proposed for the identification of relevant biological processes modulated by oxidative stress stimuli. PMID:27613049

  20. Interresidue carbonyl-carbonyl polarization transfer experiments in uniformly 13C, 15N-labeled peptides and proteins

    NASA Astrophysics Data System (ADS)

    Janik, Rafal; Ritz, Emily; Gravelle, Andrew; Shi, Lichi; Peng, Xiaohu; Ladizhansky, Vladimir

    2010-03-01

    In this work, we demonstrate that Homonuclear Rotary Resonance Recoupling (HORROR) can be used to reintroduce carbonyl-carbonyl interresidue dipolar interactions and to achieve efficient polarization transfer between carbonyl atoms in uniformly 13C, 15N-labeled peptides and proteins. We show that the HORROR condition is anisotropically broadened and overall shifted to higher radio frequency intensities because of the CSA effects. These effects are analyzed theoretically using Average Hamiltonian Theory. At spinning frequencies used in this study, 22 kHz, this broadening is experimentally found to be on the order of a kilohertz at a proton field of 600 MHz. To match HORROR condition over all powder orientations, variable amplitude radio frequency (RF) fields are required, and efficient direct transfers on the order of 20-30% can be straightforwardly established. Two- and three-dimensional chemical shift correlation experiments establishing long-range interresidue connectivities (e.g., (N[i]-CO[i - 2])) are demonstrated on the model peptide N-acetyl-valine-leucine, and on the third immunoglobulin binding domain of protein G. Possible future developments are discussed.

  1. Interresidue carbonyl-carbonyl polarization transfer experiments in uniformly 13C,15N-labeled peptides and proteins.

    PubMed

    Janik, Rafal; Ritz, Emily; Gravelle, Andrew; Shi, Lichi; Peng, Xiaohu; Ladizhansky, Vladimir

    2010-03-01

    In this work, we demonstrate that Homonuclear Rotary Resonance Recoupling (HORROR) can be used to reintroduce carbonyl-carbonyl interresidue dipolar interactions and to achieve efficient polarization transfer between carbonyl atoms in uniformly (13)C,(15)N-labeled peptides and proteins. We show that the HORROR condition is anisotropically broadened and overall shifted to higher radio frequency intensities because of the CSA effects. These effects are analyzed theoretically using Average Hamiltonian Theory. At spinning frequencies used in this study, 22kHz, this broadening is experimentally found to be on the order of a kilohertz at a proton field of 600MHz. To match HORROR condition over all powder orientations, variable amplitude radio frequency (RF) fields are required, and efficient direct transfers on the order of 20-30% can be straightforwardly established. Two- and three-dimensional chemical shift correlation experiments establishing long-range interresidue connectivities (e.g., (N[i]-CO[i-2])) are demonstrated on the model peptide N-acetyl-valine-leucine, and on the third immunoglobulin binding domain of protein G. Possible future developments are discussed. PMID:20060344

  2. Paraquat exposure and Sod2 knockdown have dissimilar impacts on the Drosophila melanogaster carbonylated protein proteome

    PubMed Central

    Narayanasamy, Suresh K.; Simpson, David C.; Martin, Ian; Grotewiel, Mike; Gronert, Scott

    2014-01-01

    Exposure to Paraquat and RNA interference knockdown of Mn or mitochondrial superoxide dismutase (Sod2) are known to result in significant lifespan reduction, locomotor dysfunction, and mitochondrial degeneration in Drosophila melanogaster. Both perturbations increase the flux of the progenitor ROS, superoxide, but the molecular underpinnings of the resulting phenotypes are poorly understood. Improved understanding of such processes could lead to advances in the treatment of numerous age-related disorders. Superoxide toxicity can act through protein carbonylation. Analysis of carbonylated proteins is attractive since carbonyl groups are not present in the twenty canonical amino acids and are amenable to labeling and enrichment strategies. Here, carbonylated proteins were labeled with biotin hydrazide and enriched on streptavidin beads. On-bead digestion was used to release carbonylated protein peptides, with relative abundance ratios versus controls obtained using the iTRAQ MS-based proteomics approach. Western blotting and biotin quantitation assay approaches were also investigated. By both western blotting and proteomics, Paraquat exposure, but not Sod2 knockdown, resulted in increased carbonylated protein relative abundance. For Paraquat exposure versus control, the median carbonylated protein relative abundance ratio (1.53) determined using MS-based proteomics was in good agreement with that obtained using a commercial biotin quantitation kit (1.36). PMID:25091824

  3. Proteomic analysis of carbonylated proteins in the monkey substantia nigra after ischemia-reperfusion.

    PubMed

    Oikawa, Shinji; Kobayashi, Hatasu; Kitamura, Yuki; Zhu, Hong; Obata, Kumi; Minabe, Yoshio; Dazortsava, Maryia; Ohashi, Kyoko; Tada-Oikawa, Saeko; Takahashi, Hitoshi; Yata, Kenichiro; Murata, Mariko; Yamashima, Tetsumori

    2014-06-01

    In Parkinson's disease (PD), oxidative stresses cause cell death of dopaminergic neurons of the substantia nigra (SN), but its molecular mechanism still remains unclarified. Our previous study of proteomic analysis in the monkey CA1 hippocampus after ischemia-reperfusion revealed reactive oxygen species (ROS)-induced carbonyl modification of a molecular chaperone, heat shock 70-kDa protein 1 (Hsp70.1), especially in its key site, Arg469. Here, to clarify the mechanism of neurodegeneration in PD, the SN tissue of the same monkey experimental paradigm was studied for identifying and characterizing carbonylated proteins by the two-dimensional gel electrophoresis with immunochemical detection of protein carbonyls (2D Oxyblot). We found carbonyl modification not only of Hsp70.1 but also of mitochondrial aconitase, dihydropyrimidinase-related protein 2, T-complex protein 1 subunit alpha, dihydrolipoyl dehydrogenase, fructose-bisphosphate aldolase C, glutamate dehydrogenase 1, and aspartate aminotransferase. Intriguingly, in the SN also, the carbonylation site of Hsp70.1 was identified to be Arg469. Since Hsp70.1 is recently known to stabilize the lysosomal membrane, its oxidative injury conceivably plays an important role in the ROS-mediated neuronal cell death by inducing lysosomal destabilization. Implications of each carbonylated proteins for the dopaminergic neuronal death were discussed, in comparison with the CA1 neuronal death. PMID:24697733

  4. Carbonylation of myofibrillar proteins through the maillard pathway: effect of reducing sugars and reaction temperature.

    PubMed

    Villaverde, Adriana; Estévez, Mario

    2013-03-27

    Carbonylation is recognized as one of the most remarkable chemical modifications in oxidized proteins and is generally ascribed to the direct attack of free radicals to basic amino acid residues. The purpose of this work was to investigate the formation of specific carbonyls, α-aminoadipic and γ-glutamic semialdehydes (AAS and GGS, respectively), in myofibrillar proteins (MP) through a Maillard-type pathway in the presence of reducing sugars. The present study confirmed the concurrent formation of protein carbonyls and advanced glycation end-products (AGEs) during incubation (80 °C/48 h) of MP (4 mg/mL) in the presence of reducing sugars (0.5 M). Copper irons (10 μM) were found to promote the formation of protein carbonyls, and a specific inhibitor of the Maillard reaction (0.02 M pyridoxamine) blocked the carbonylation process which emphasize the occurrence of a Maillard-type pathway. The Maillard-mediated carbonylation occurred in a range of reducing sugars (0.02-0.5 M) and reaction temperatures (4-110 °C) compatible with food systems. Upcoming studies on this topic may contribute further to shed light on the complex interactions between protein oxidation and the Maillard reaction and the impact of the protein damage on food quality and human health.

  5. Proteomic identification of carbonylated proteins in F344 rat hippocampus after 1-bromopropane exposure

    SciTech Connect

    Huang, Zhenlie; Ichihara, Sahoko; Oikawa, Shinji; Chang, Jie; Zhang, Lingyi; Subramanian, Kaviarasan; Mohideen, Sahabudeen Sheik; Ichihara, Gaku

    2012-08-15

    1-Bromopropane (1-BP) is neurotoxic in both experimental animals and humans. Previous proteomic analysis of rat hippocampus implicated alteration of protein expression in oxidative stress, suggesting that oxidative stress plays a role in 1-BP-induced neurotoxicity. To understand this role at the protein level, we exposed male F344 rats to 1-BP at 0, 400, or 1000 ppm for 8 h/day for 1 week or 4 weeks by inhalation and quantitated changes in hippocampal protein carbonyl using a protein carbonyl assay, two-dimensional gel electrophoresis (2-DE), immunoblotting, and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF/MS). Hippocampal reactive oxygen species and protein carbonyl were significantly increased, demonstrating 1-BP-associated induction of oxidative stress and protein damage. MALDI-TOF-TOF/MS identified 10 individual proteins with increased carbonyl modification (p < 0.05; fold-change ≥ 1.5). The identified proteins were involved in diverse biological processes including glycolysis, ATP production, tyrosine catabolism, GTP binding, guanine degradation, and neuronal metabolism of dopamine. Hippocampal triosephosphate isomerase (TPI) activity was significantly reduced and negatively correlated with TPI carbonylation (p < 0.001; r = 0.83). Advanced glycation end-product (AGE) levels were significantly elevated both in the hippocampus and plasma, and hippocampal AGEs correlated negatively with TPI activity (p < 0.001; r = 0.71). In conclusion, 1-BP-induced neurotoxicity in the rat hippocampus seems to involve oxidative damage of cellular proteins, decreased TPI activity, and elevated AGEs. -- Highlights: ► 1-BP increases hippocampal ROS levels and hippocampal and plasma protein carbonyls. ► 1-BP increases TPI carbonylation and decreases TPI activity in the hippocampus. ► 1-BP increases hippocampal and plasma AGE levels.

  6. Protein carbonyl formation in response to propiconazole-induced oxidative stress.

    PubMed

    Bruno, Maribel; Moore, Tanya; Nesnow, Stephen; Ge, Yue

    2009-04-01

    Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propiconazole-induced toxicity. To understand the contribution of oxidative stress on toxicity at the protein level, we developed an integrated approach for the systematic measurement of protein oxidation in the livers from propiconazole-treated mice. Liver protein carbonylation increased significantly after treatment with propiconazole, demonstrating propiconazole-associated induction of oxidative stress. Utilizing two-dimensional gel electrophoresis (2-DE), immunoblotting, and mass spectrometry, we identified 17 carbonylated proteins that were altered with varying intensities by propiconazole treatment. The potential effects of protein carbonylation on protein functions and cellular activities in the liver of propiconazole-treated mice were further investigated. A significant negative correlation between protein carbonylation and cytochrome c reductase activity was found. We conclude that glycolysis, mitochondrial respiratory chain, ATP production, amino acid metabolism, CO2 hydration, cellular antioxidant defense and detoxification system, and tetrahydrobiopterin pathways are affected by oxygen radicals in the livers of propiconazole-treated mice. This study suggests a mode of propiconazole-induced toxicity in mouse liver which primarily involves oxidative damage to cellular proteins.

  7. Hepatocellular carcinoma protein carbonylation in virus C and metabolic syndrome patients.

    PubMed

    Martin, Fernando Ariel; Mebarki, Mouniya; Paradis, Valérie; Friguet, Bertrand; Radman, Miroslav

    2014-10-01

    Metabolic syndrome (MS) is becoming the leading cause of chronic liver diseases worldwide. Hepatocellular carcinoma (HCC) development in MS is peculiar compared to other chronic liver diseases. Carbohydrate and lipid metabolic imbalance in MS increase reactive oxygen species damaging proteins. In the present work we study the difference in protein oxidative damage (carbonylation) in human HCC derived from virus C infection (VHC) and from MS (MS_HCC) as the only subjacent cause. We selected a patient cohort containing of 10 non-tumoral and 10 tumoral liver resections in each study group (virus C and MS HCC) based on clinical patient history and histological parameters. Protein samples were labeled to saturation using CF 647-hydrazide™ dye. This approach allows us to perform carbonyl detection alongside with a DIGE experiment. We detected a total of 1184 spots with 36 differentially expressed proteins and 47 spots differentially carbonylated between VHC and MS_HCC (fold change >1.5, p<0.05). VHC up-regulated proteins are involved in signaling pathways related to cancer development such as signaling by EGFR, Wnt, Cdc20 and cell cycle. Further, up-regulated proteins in MS HCC, are implicated in metabolism of carbohydrates and amino acids. Differential carbonylation analysis between VHC and MS_HCC showed protein damage in proteins such as glucose phosphate isomerase, isocitrate dehydrogenase, and 3-ketoacyl-CoA thiolase. Higher protein carbonylation in MS_HCC samples was observed in proteins involved in redox response and lipid metabolism. In conclusion, the observed difference in protein oxidative damage between MS and Virus C derived carcinoma could account for the different cancer development pathway. PMID:26461368

  8. Protein targets for carbonylation by 4-hydroxy-2-nonenal in rat liver mitochondria

    PubMed Central

    Guo, Jia; Prokai-Tatrai, Katalin; Ngyuen, Vien; Rauniyar, Navin; Ughy, Bettina; Prokai, Laszlo

    2011-01-01

    Protein carbonylation has been associated with various pathophysiological processes. A representative reactive carbonyl species (RCS), 4-hydroxy-2-nonenal (HNE), has been implicated specifically as a causative factor for the initiation and/or progression of various diseases. To date, however, little is known about the proteins and their modification sites susceptible to “carbonyl stress” by this RCS, especially in the liver. Using chemoprecipitation based on a solid phase hydrazine chemistry coupled with LC-MS/MS bottom-up approach and database searching, we identified several protein-HNE adducts in isolated rat liver mitochondria upon HNE exposure. The identification of selected major protein targets, such as the ATP synthase β-subunit, was further confirmed by immunoblotting and a gel-based approach in combination with LC–MS/MS. A network was also created based on the identified protein targets that showed that the main protein interactions were associated with cell death, tumor morphology and drug metabolism, implicating the toxic nature of HNE in the liver mitoproteome. The functional consequence of carbonylation was illustrated by its detrimental impact on the activity of ATP synthase, a representative major mitochondrial protein target for HNE modifications. PMID:21801862

  9. Dormancy alleviation by NO or HCN leading to decline of protein carbonylation levels in apple (Malus domestica Borkh.) embryos.

    PubMed

    Krasuska, Urszula; Ciacka, Katarzyna; Dębska, Karolina; Bogatek, Renata; Gniazdowska, Agnieszka

    2014-08-15

    Deep dormancy of apple (Malus domestica Borkh.) embryos can be overcome by short-term pre-treatment with nitric oxide (NO) or hydrogen cyanide (HCN). Dormancy alleviation of embryos modulated by NO or HCN and the first step of germination depend on temporary increased production of reactive oxygen species (ROS). Direct oxidative attack on some amino acid residues or secondary reactions via reactive carbohydrates and lipids can lead to the formation of protein carbonyl derivatives. Protein carbonylation is a widely accepted covalent and irreversible modification resulting in inhibition or alteration of enzyme/protein activities. It also increases the susceptibility of proteins to proteolytic degradation. The aim of this work was to investigate protein carbonylation in germinating apple embryos, the dormancy of which was removed by pre-treatment with NO or HCN donors. It was performed using a quantitative spectrophotometric method, while patterns of carbonylated protein in embryo axes were analyzed by immunochemical techniques. The highest concentration of protein carbonyl groups was observed in dormant embryos. It declined in germinating embryos pre-treated with NO or HCN, suggesting elevated degradation of modified proteins during seedling formation. A decrease in the concentration of carbonylated proteins was accompanied by modification in proteolytic activity in germinating apple embryos. A strict correlation between the level of protein carbonyl groups and cotyledon growth and greening was detected. Moreover, direct in vitro carbonylation of BSA treated with NO or HCN donors was analyzed, showing action of both signaling molecules as protein oxidation agents. PMID:24973585

  10. Dormancy alleviation by NO or HCN leading to decline of protein carbonylation levels in apple (Malus domestica Borkh.) embryos.

    PubMed

    Krasuska, Urszula; Ciacka, Katarzyna; Dębska, Karolina; Bogatek, Renata; Gniazdowska, Agnieszka

    2014-08-15

    Deep dormancy of apple (Malus domestica Borkh.) embryos can be overcome by short-term pre-treatment with nitric oxide (NO) or hydrogen cyanide (HCN). Dormancy alleviation of embryos modulated by NO or HCN and the first step of germination depend on temporary increased production of reactive oxygen species (ROS). Direct oxidative attack on some amino acid residues or secondary reactions via reactive carbohydrates and lipids can lead to the formation of protein carbonyl derivatives. Protein carbonylation is a widely accepted covalent and irreversible modification resulting in inhibition or alteration of enzyme/protein activities. It also increases the susceptibility of proteins to proteolytic degradation. The aim of this work was to investigate protein carbonylation in germinating apple embryos, the dormancy of which was removed by pre-treatment with NO or HCN donors. It was performed using a quantitative spectrophotometric method, while patterns of carbonylated protein in embryo axes were analyzed by immunochemical techniques. The highest concentration of protein carbonyl groups was observed in dormant embryos. It declined in germinating embryos pre-treated with NO or HCN, suggesting elevated degradation of modified proteins during seedling formation. A decrease in the concentration of carbonylated proteins was accompanied by modification in proteolytic activity in germinating apple embryos. A strict correlation between the level of protein carbonyl groups and cotyledon growth and greening was detected. Moreover, direct in vitro carbonylation of BSA treated with NO or HCN donors was analyzed, showing action of both signaling molecules as protein oxidation agents.

  11. Shotgun Redox Proteomics: Identification and Quantitation of Carbonylated Proteins in the UVB-Resistant Marine Bacterium, Photobacterium angustum S14

    PubMed Central

    Matallana-Surget, Sabine; Cavicchioli, Ricardo; Fauconnier, Charles; Wattiez, Ruddy; Leroy, Baptiste; Joux, Fabien; Raftery, Mark J.; Lebaron, Philippe

    2013-01-01

    UVB oxidizes proteins through the generation of reactive oxygen species. One consequence of UVB irradiation is carbonylation, the irreversible formation of a carbonyl group on proline, lysine, arginine or threonine residues. In this study, redox proteomics was performed to identify carbonylated proteins in the UVB resistant marine bacterium Photobacterium angustum. Mass-spectrometry was performed with either biotin-labeled or dinitrophenylhydrazide (DNPH) derivatized proteins. The DNPH redox proteomics method enabled the identification of 62 carbonylated proteins (5% of 1221 identified proteins) in cells exposed to UVB or darkness. Eleven carbonylated proteins were quantified and the UVB/dark abundance ratio was determined at both the protein and peptide levels. As a result we determined which functional classes of proteins were carbonylated, which residues were preferentially modified, and what the implications of the carbonylation were for protein function. As the first large scale, shotgun redox proteomics analysis examining carbonylation to be performed on bacteria, our study provides a new level of understanding about the effects of UVB on cellular proteins, and provides a methodology for advancing studies in other biological systems. PMID:23874515

  12. Mitochondrial ATP synthase is a target for TNBS-induced protein carbonylation in XS-106 dendritic cells.

    PubMed

    Je, Jeong Hwan; Lee, Tae Hyung; Kim, Dong Hyun; Cho, Young Hun; Lee, Ju Hee; Kim, Soo Chan; Lee, Sang-Kyou; Lee, Jaewon; Lee, Min-Geol

    2008-06-01

    ROS are produced in dendritic cells (DCs) during antigen presentation in contact hypersensitivity (CHS). As a result, ROS cause a number of nonenzymatic protein modifications, including carbonylation, which is the most widely used marker of oxidative stress. 2,4,6-Trinitrobenzene sulfonic acid (TNBS) is a well-characterized contact allergen that results in the formation of ROS. However, proteins that are carbonylated in DCs in response to TNBS have not been identified. To study ROS-dependent protein carbonylation in response to TNBS, we used the well-established mouse DC line, XS-106. We focused on the effects of TNBS on oxidation by examining selected oxidative markers. We identified TNBS-induced ROS and myeloperoxidase (MPO) proteins and demonstrated that the increase in ROS resulted in IL-12 production. The increase in oxidation was further confirmed by an oxidation-dependent increase in protein modifications, such as carbonylation. In fact, TNBS strongly induced carbonylation of mitochondrial adenosine triphosphate (ATP) synthase in XS-106 DCs, as determined by MALDI-TOF analysis and 2-D Western blotting. ROS production and protein carbonylation were confirmed in human monocyte-derived DCs (Mo-DCs). Furthermore, glutathione (GSH) decreased ROS and protein carbonylation in Mo-DCs. Carbonylation of ATP synthase in DCs may contribute to the pathophysiology of CHS.

  13. Chaperone heat shock protein 90 mobilization and hydralazine cytoprotection against acrolein-induced carbonyl stress.

    PubMed

    Burcham, Philip C; Raso, Albert; Kaminskas, Lisa M

    2012-11-01

    Toxic carbonyls such as acrolein participate in many degenerative diseases. Although the nucleophilic vasodilatory drug hydralazine readily traps such species under "test-tube" conditions, whether these reactions adequately explain its efficacy in animal models of carbonyl-mediated disease is uncertain. We have previously shown that hydralazine attacks carbonyl-adducted proteins in an "adduct-trapping" reaction that appears to take precedence over direct "carbonyl-sequestering" reactions, but how this reaction conferred cytoprotection was unclear. This study explored the possibility that by increasing the bulkiness of acrolein-adducted proteins, adduct-trapping might alter the redistribution of chaperones to damaged cytoskeletal proteins that are known targets for acrolein. Using A549 lung adenocarcinoma cells, the levels of chaperones heat shock protein (Hsp) 40, Hsp70, Hsp90, and Hsp110 were measured in intermediate filament extracts prepared after a 3-h exposure to acrolein. Exposure to acrolein alone modestly increased the levels of all four chaperones. Coexposure to hydralazine (10-100 μM) strongly suppressed cell ATP loss while producing strong adduct-trapping in intermediate filaments. Most strikingly, hydralazine selectively boosted the levels of cytoskeletal-associated Hsp90, including a high-mass species that was sensitive to the Hsp90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin. Biochemical fractionation of acrolein- and hydralazine-treated cells revealed that hydralazine likely promoted Hsp90 migration from cytosol into other subcellular compartments. A role for Hsp90 mobilization in cytoprotection was confirmed by the finding that brief heat shock treatment suppressed acute acrolein toxicity in A549 cells. Taken together, these findings suggest that by increasing the steric bulk of carbonyl-adducted proteins, adduct-trapping drugs trigger the intracellular mobilization of the key molecular chaperone Hsp90.

  14. Impact of lipid content and composition on lipid oxidation and protein carbonylation in experimental fermented sausages.

    PubMed

    Fuentes, Verónica; Estévez, Mario; Ventanas, Jesús; Ventanas, Sonia

    2014-03-15

    This study aims to investigate the effect of lipid content (∼4%, ∼10% and ∼15%) and composition (different lipid sources; animal fat and sunflower oil) on the oxidative stability of proteins and lipids in experimental fermented sausages. Increasing the lipid content of sausages enhanced the susceptibility of lipids to oxidation whereas the effect on the formation of specific carbonyls from protein oxidation was not so evident. Sausages manufactured with different lipid sources affected the susceptibility of lipids and proteins to oxidation as a likely result of the modifications in the fatty acid profile, as well as to the presence of antioxidant compounds. While the fatty acid profile had a major effect on the occurrence and extent of lipid oxidation, the presence of compounds with potential antioxidant activity may be more influential on the extent of protein carbonylation.

  15. Cell age dependent concentration of Escherichia coli divisome proteins analyzed with ImageJ and ObjectJ.

    PubMed

    Vischer, Norbert O E; Verheul, Jolanda; Postma, Marten; van den Berg van Saparoea, Bart; Galli, Elisa; Natale, Paolo; Gerdes, Kenn; Luirink, Joen; Vollmer, Waldemar; Vicente, Miguel; den Blaauwen, Tanneke

    2015-01-01

    The rod-shaped Gram-negative bacterium Escherichia coli multiplies by elongation followed by binary fission. Longitudinal growth of the cell envelope and synthesis of the new poles are organized by two protein complexes called elongasome and divisome, respectively. We have analyzed the spatio-temporal localization patterns of many of these morphogenetic proteins by immunolabeling the wild type strain MC4100 grown to steady state in minimal glucose medium at 28°C. This allowed the direct comparison of morphogenetic protein localization patterns as a function of cell age as imaged by phase contrast and fluorescence wide field microscopy. Under steady state conditions the age distribution of the cells is constant and is directly correlated to cell length. To quantify cell size and protein localization parameters in 1000s of labeled cells, we developed 'Coli-Inspector,' which is a project running under ImageJ with the plugin 'ObjectJ.' ObjectJ organizes image-analysis tasks using an integrated approach with the flexibility to produce different output formats from existing markers such as intensity data and geometrical parameters. ObjectJ supports the combination of automatic and interactive methods giving the user complete control over the method of image analysis and data collection, with visual inspection tools for quick elimination of artifacts. Coli-inspector was used to sort the cells according to division cycle cell age and to analyze the spatio-temporal localization pattern of each protein. A unique dataset has been created on the concentration and position of the proteins during the cell cycle. We show for the first time that a subset of morphogenetic proteins have a constant cellular concentration during the cell division cycle whereas another set exhibits a cell division cycle dependent concentration variation. Using the number of proteins present at midcell, the stoichiometry of the divisome is discussed.

  16. Cell age dependent concentration of Escherichia coli divisome proteins analyzed with ImageJ and ObjectJ.

    PubMed

    Vischer, Norbert O E; Verheul, Jolanda; Postma, Marten; van den Berg van Saparoea, Bart; Galli, Elisa; Natale, Paolo; Gerdes, Kenn; Luirink, Joen; Vollmer, Waldemar; Vicente, Miguel; den Blaauwen, Tanneke

    2015-01-01

    The rod-shaped Gram-negative bacterium Escherichia coli multiplies by elongation followed by binary fission. Longitudinal growth of the cell envelope and synthesis of the new poles are organized by two protein complexes called elongasome and divisome, respectively. We have analyzed the spatio-temporal localization patterns of many of these morphogenetic proteins by immunolabeling the wild type strain MC4100 grown to steady state in minimal glucose medium at 28°C. This allowed the direct comparison of morphogenetic protein localization patterns as a function of cell age as imaged by phase contrast and fluorescence wide field microscopy. Under steady state conditions the age distribution of the cells is constant and is directly correlated to cell length. To quantify cell size and protein localization parameters in 1000s of labeled cells, we developed 'Coli-Inspector,' which is a project running under ImageJ with the plugin 'ObjectJ.' ObjectJ organizes image-analysis tasks using an integrated approach with the flexibility to produce different output formats from existing markers such as intensity data and geometrical parameters. ObjectJ supports the combination of automatic and interactive methods giving the user complete control over the method of image analysis and data collection, with visual inspection tools for quick elimination of artifacts. Coli-inspector was used to sort the cells according to division cycle cell age and to analyze the spatio-temporal localization pattern of each protein. A unique dataset has been created on the concentration and position of the proteins during the cell cycle. We show for the first time that a subset of morphogenetic proteins have a constant cellular concentration during the cell division cycle whereas another set exhibits a cell division cycle dependent concentration variation. Using the number of proteins present at midcell, the stoichiometry of the divisome is discussed. PMID:26124755

  17. Cell age dependent concentration of Escherichia coli divisome proteins analyzed with ImageJ and ObjectJ

    PubMed Central

    Vischer, Norbert O. E.; Verheul, Jolanda; Postma, Marten; van den Berg van Saparoea, Bart; Galli, Elisa; Natale, Paolo; Gerdes, Kenn; Luirink, Joen; Vollmer, Waldemar; Vicente, Miguel; den Blaauwen, Tanneke

    2015-01-01

    The rod-shaped Gram-negative bacterium Escherichia coli multiplies by elongation followed by binary fission. Longitudinal growth of the cell envelope and synthesis of the new poles are organized by two protein complexes called elongasome and divisome, respectively. We have analyzed the spatio-temporal localization patterns of many of these morphogenetic proteins by immunolabeling the wild type strain MC4100 grown to steady state in minimal glucose medium at 28°C. This allowed the direct comparison of morphogenetic protein localization patterns as a function of cell age as imaged by phase contrast and fluorescence wide field microscopy. Under steady state conditions the age distribution of the cells is constant and is directly correlated to cell length. To quantify cell size and protein localization parameters in 1000s of labeled cells, we developed ‘Coli-Inspector,’ which is a project running under ImageJ with the plugin ‘ObjectJ.’ ObjectJ organizes image-analysis tasks using an integrated approach with the flexibility to produce different output formats from existing markers such as intensity data and geometrical parameters. ObjectJ supports the combination of automatic and interactive methods giving the user complete control over the method of image analysis and data collection, with visual inspection tools for quick elimination of artifacts. Coli-inspector was used to sort the cells according to division cycle cell age and to analyze the spatio-temporal localization pattern of each protein. A unique dataset has been created on the concentration and position of the proteins during the cell cycle. We show for the first time that a subset of morphogenetic proteins have a constant cellular concentration during the cell division cycle whereas another set exhibits a cell division cycle dependent concentration variation. Using the number of proteins present at midcell, the stoichiometry of the divisome is discussed. PMID:26124755

  18. Is extinction age dependent?

    USGS Publications Warehouse

    Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.

    2006-01-01

    Age-dependent extinction is an observation with important biological implications. Van Valen's Red Queen hypothesis triggered three decades of research testing its primary implication: that age is independent of extinction. In contrast to this, later studies with species-level data have indicated the possible presence of age dependence. Since the formulation of the Red Queen hypothesis, more powerful tests of survivorship models have been developed. This is the first report of the application of the Cox Proportional Hazards model to paleontological data. Planktonic foraminiferal morphospecies allow the taxonomic and precise stratigraphic resolution necessary for the Cox model. As a whole, planktonic foraminiferal morphospecies clearly show age-dependent extinction. In particular, the effect is attributable to the presence of shorter-ranged species (range < 4 myr) following extinction events. These shorter-ranged species also possess tests with unique morphological architecture. The morphological differences are probably epiphenomena of underlying developmental and heterochronic processes of shorter-ranged species that survived various extinction events. Extinction survivors carry developmental and morphological characteristics into postextinction recovery times, and this sets them apart from species populations established independently of extinction events. Copyright ?? 2006, SEPM (Society for Sedimentary Geology).

  19. A Filtered Database Search Algorithm for Endogenous Serum Protein Carbonyl Modifications in a Mouse Model of Inflammation*

    PubMed Central

    Slade, Peter G.; Williams, Michelle V.; Chiang, Alison; Iffrig, Elizabeth; Tannenbaum, Steven R.; Wishnok, John S.

    2011-01-01

    During inflammation, the resulting oxidative stress can damage surrounding host tissue, forming protein-carbonyls. The SJL mouse is an experimental animal model used to assess in vivo toxicological responses to reactive oxygen and nitrogen species from inflammation. The goals of this study were to identify the major serum proteins modified with a carbonyl functionality and to identify the types of carbonyl adducts. To select for carbonyl-modified proteins, serum proteins were reacted with an aldehyde reactive probe that biotinylated the carbonyl modification. Modified proteins were enriched by avidin affinity and identified by two-dimensional liquid chromatography tandem MS. To identify the carbonyl modification, tryptic peptides from serum proteins were subjected to avidin affinity and the enriched modified peptides were analyzed by liquid chromatography tandem MS. It was noted that the aldehyde reactive probe tag created tag-specific fragment ions and neutral losses, and these extra features in the mass spectra inhibited identification of the modified peptides by database searching. To enhance the identification of carbonyl-modified peptides, a program was written that used the tag-specific fragment ions as a fingerprint (in silico filter program) and filtered the mass spectrometry data to highlight only modified peptides. A de novo-like database search algorithm was written (biotin peptide identification program) to identify the carbonyl-modified peptides. Although written specifically for our experiments, this software can be adapted to other modification and enrichment systems. Using these routines, a number of lipid peroxidation-derived protein carbonyls and direct side-chain oxidation proteins carbonyls were identified in SJL mouse serum. PMID:21768395

  20. Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles

    PubMed Central

    Batista, Thiago Martins; Tomiyoshi, Lilian Midori; Dias, Ana Carolina; Roma, Letícia Prates; Módulo, Carolina Maria; Malki, Leonardo Tannus; Filho, Elísio Bueno Machado; Deminice, Rafael; Jordão, Alceu Afonso; Cunha, Daniel A.

    2012-01-01

    Purpose Anti-oxidation and exocytosis are important for maintaining exocrine tissue homeostasis. During aging, functional and structural alterations occur in the lacrimal gland (LG), including oxidative damage to proteins, lipids, and DNA. The aims of the present study were to determine in the aging LG: a) the effects of aging on LG structure and secretory activity and b) changes in the expression of oxidative stress markers. Methods To address these goals, tear secretion composition and corneal impression cytology were compared between male Wistar rats of 2 (control) and 24 (aged) months. LG morphology and the expression levels of vitamin E and malonaldehyde (MDA) were evaluated to determine the anti-oxidant activity and lipid peroxidation, respectively. RT–PCR and western blot analysis were used for the analysis of Ras related in brain GTPase protein (Rab) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the secretory machinery (i.e.; Rab 3d, Rab 27, vesicle-associated membrane protein-2 (Vamp-2), and syntaxin). Results Histological analysis of aged rats revealed a higher frequency of corneal epithelia metaplasia. In the acinar cells, organelles underwent degeneration, and lipofucsin-like material accumulated in the cytoplasm along with declines in the anti-oxidant marker vitamin E. Rab3d and Rab27b mRNA levels fell along with Rab3d protein expression, whereas syntaxin levels increased. Conclusions These findings indicate that exocytotic and anti-oxidant mechanisms become impaired with age in the rat LG. In parallel with these structural alterations, functional declines may contribute to the pathophysiology caused by tear film modification in dry eye disease. PMID:22312187

  1. Identification, quantification, and functional aspects of skeletal muscle protein-carbonylation in vivo during acute oxidative stress.

    PubMed

    Fedorova, Maria; Kuleva, Nadezhda; Hoffmann, Ralf

    2010-05-01

    Reactive oxidative species (ROS) play important roles in cellular signaling but can also modify and often functionally inactivate other biomolecules. Thus, cells have developed effective enzymatic and nonenzymatic strategies to scavenge ROS. However, under oxidative stress, ROS production is able to overwhelm the scavenging systems, increasing the levels of functionally impaired proteins. A major class of irreversible oxidative modifications is carbonylation, which refers to reactive carbonyl-groups. In this investigation, we have studied the production and clearance rates for skeletal muscle proteins in a rat model of acute oxidative stress over a time period of 24 h using a gel-based proteomics approach. Optimized ELISA and Western blots with 10-fold improved sensitivities showed that the carbonylation level was stable at 4 nmol per mg protein 3 h following ROS induction. The carbonylation level then increased 3-fold over 6 h and then remained stable. In total, the oxidative stress changed the steady state levels of 20 proteins and resulted in the carbonylation of 38 skeletal muscle proteins. Carbonylation of these proteins followed diverse kinetics with some proteins being highly carbonylated very quickly, whereas others peaked in the 9 h sample or continued to increase up to 24 h after oxidative stress was induced. PMID:20377239

  2. On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures.

    PubMed

    Bartlett, Gail J; Woolfson, Derek N

    2016-04-01

    Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals' interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone-carbonyl oxygen atoms located within α-helices and β-sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone-carbonyl oxygen atoms from a set of high-resolution protein structures and associated molecular-dynamics simulations in water. We included more-recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα-H bonds and methyl-H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone-carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α- and β-structure. In addition, we find examples of under- and over-satisfied carbonyl-oxygen atoms, and we identify both sequence-dependent and sequence-independent secondary-structural motifs in which these reside. Our analysis provides a more-detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design. PMID:26833776

  3. On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures.

    PubMed

    Bartlett, Gail J; Woolfson, Derek N

    2016-04-01

    Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals' interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone-carbonyl oxygen atoms located within α-helices and β-sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone-carbonyl oxygen atoms from a set of high-resolution protein structures and associated molecular-dynamics simulations in water. We included more-recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα-H bonds and methyl-H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone-carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α- and β-structure. In addition, we find examples of under- and over-satisfied carbonyl-oxygen atoms, and we identify both sequence-dependent and sequence-independent secondary-structural motifs in which these reside. Our analysis provides a more-detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design.

  4. Mitochondrial ascorbate-glutathione cycle and proteomic analysis of carbonylated proteins during tomato (Solanum lycopersicum) fruit ripening.

    PubMed

    López-Vidal, O; Camejo, D; Rivera-Cabrera, F; Konigsberg, M; Villa-Hernández, J M; Mendoza-Espinoza, J A; Pérez-Flores, L J; Sevilla, F; Jiménez, A; Díaz de León-Sánchez, F

    2016-03-01

    In non-photosynthetic tissues, mitochondria are the main source of energy and of reactive oxygen species. Accumulation of high levels of these species in the cell causes damage to macromolecules including several proteins and induces changes in different metabolic processes. Fruit ripening has been characterized as an oxidative phenomenon; therefore, control of reactive oxygen species levels by mitochondrial antioxidants plays a crucial role on this process. In this work, ascorbate-glutathione cycle components, hydrogen peroxide levels and the proteomic profile of carbonylated proteins were analyzed in mitochondria isolated from tomato (Solanum lycopersicum) fruit at two ripening stages. A significant increase on most ascorbate-glutathione cycle components and on carbonylated proteins was observed in mitochondria from breaker to light red stage. Enzymes and proteins involved in diverse cellular and mitochondrial metabolic pathways were identified among the carbonylated proteins. These results suggest that protein carbonylation is a post-translational modification involved in tomato fruit ripening regulation. PMID:26471654

  5. Mitochondrial ascorbate-glutathione cycle and proteomic analysis of carbonylated proteins during tomato (Solanum lycopersicum) fruit ripening.

    PubMed

    López-Vidal, O; Camejo, D; Rivera-Cabrera, F; Konigsberg, M; Villa-Hernández, J M; Mendoza-Espinoza, J A; Pérez-Flores, L J; Sevilla, F; Jiménez, A; Díaz de León-Sánchez, F

    2016-03-01

    In non-photosynthetic tissues, mitochondria are the main source of energy and of reactive oxygen species. Accumulation of high levels of these species in the cell causes damage to macromolecules including several proteins and induces changes in different metabolic processes. Fruit ripening has been characterized as an oxidative phenomenon; therefore, control of reactive oxygen species levels by mitochondrial antioxidants plays a crucial role on this process. In this work, ascorbate-glutathione cycle components, hydrogen peroxide levels and the proteomic profile of carbonylated proteins were analyzed in mitochondria isolated from tomato (Solanum lycopersicum) fruit at two ripening stages. A significant increase on most ascorbate-glutathione cycle components and on carbonylated proteins was observed in mitochondria from breaker to light red stage. Enzymes and proteins involved in diverse cellular and mitochondrial metabolic pathways were identified among the carbonylated proteins. These results suggest that protein carbonylation is a post-translational modification involved in tomato fruit ripening regulation.

  6. Proteomic profile of carbonylated proteins in rat liver: exercise attenuated oxidative stress may be involved in fatty liver improvement.

    PubMed

    Hu, Xiaofei; Duan, Zhigui; Hu, Hui; Li, Guolin; Yan, Siyu; Wu, Jinfeng; Wang, Jun; Yin, Dazhong; Xie, Qingji

    2013-05-01

    To screen target proteins of oxidative stress which mediate the effects of exercise on preventing nonalcoholic fatty liver disease (NAFLD), the methods for selecting carbonylated proteins were modified, and carbonylated proteins were profiled. The results showed that treadmill training reduced oxidative stress and the levels of intrahepatic triglyceride (IHTG). The changes in IHTG showed a significant positive correlation with oxidative stress as indicated by malondialdehyde level. Further results from proteomics illustrated that 17 functional proteins were susceptible to oxidative modification, and exercise protected three proteins from carbonylation. The latter three proteins may serve as both direct target proteins of oxidative stress and mediators contributing to the beneficial effects of exercise. In particular, a long-chain specific acyl-CoA dehydrogenase (ACADL) which was a key enzyme in lipid metabolism was not carbonylated and with higher activities in exercise group. These findings indicate that this modified technique is practical and powerful in selecting carbonylated proteins. Long-term treadmill training is effective in ameliorating oxidative stress and preventing the accumulation of IHTG. Among the 17 target proteins of oxidative modification, three proteins contribute to the beneficial effects of exercise. Preventing ACADL from carbonylation may be involved in the physiological mechanism of exercise-induced NAFLD improvement.

  7. Nitrite promotes protein carbonylation and Strecker aldehyde formation in experimental fermented sausages: are both events connected?

    PubMed

    Villaverde, A; Ventanas, J; Estévez, M

    2014-12-01

    The role played by curing agents (nitrite, ascorbate) on protein oxidation and Strecker aldehyde formation is studied. To fulfill this objective, increasing concentrations of nitrite (0, 75 and 150ppm) and ascorbate (0, 250 and 500ppm) were added to sausages subjected to a 54day drying process. The concurrence of intense proteolysis, protein carbonylation and formation of Strecker aldehydes during processing of sausages suggests that α-aminoadipic semialdehyde (AAS) and γ-glutamic semialdehyde (GGS) may be implicated in the formation of Strecker aldehydes. The fact that nitrite (150ppm, ingoing amount) significantly promoted the formation of protein carbonyls at early stages of processing and the subsequent formation of Strecker aldehydes provides strength to this hypothesis. Ascorbate (125 and 250ppm) controlled the overall extent of protein carbonylation in sausages without declining the formation of Strecker aldehydes. These results may contribute to understanding the chemistry fundamentals of the positive influence of nitrite on the flavor and overall acceptability of cured muscle foods.

  8. Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein.

    PubMed

    Oster-Granite, M L; McPhie, D L; Greenan, J; Neve, R L

    1996-11-01

    The molecular basis for the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature in Alzheimer's disease (AD) is incompletely understood. We have proposed that one molecule common to these abnormal processes is a fragment of the Alzheimer amyloid precursor protein (APP) comprising the C-terminal 100 amino acids of this molecule (APP-C100). We tested this hypothesis by creating transgenic mice expressing APP-C100 in the brain. We report here that aging (18-28 month) APP-C100 transgenic mice exhibit profound degeneration of neurons and synapses in Ammon's horn and the dentate gyrus of the hippocampal formation. Of the 106 transgenic mice between 8 and 28 months of age that were examined, all of those older than 18 months displayed severe hippocampal degeneration. The numerous degenerating axonal profiles contained increased numbers of neurofilaments, whorls of membrane, and accumulations of debris resembling secondary lysosomes near the cell body. The dendrites of degenerating granule and pyramidal cells contained disorganized, wavy microtubules. Cerebral blood vessels had thickened refractile basal laminae, and microglia laden with debris lay adjacent to larger venous vessels. Mice transgenic for Flag-APP-C100 (in which the hydrophilic Flag tag was fused to the N terminus of APP-C100) showed a similar degree of neurodegeneration in the hippocampal formation as early as 12 months of age. The 45 control mice displayed only occasional necrotic cells and no extensive cell degeneration in the same brain regions. These findings show that APP-C100 is capable of causing some of the neuropathological features of AD. PMID:8824314

  9. Narrow carbonyl resonances in proton-diluted proteins facilitate NMR assignments in the solid-state.

    PubMed

    Linser, Rasmus; Fink, Uwe; Reif, Bernd

    2010-05-01

    HNCO/HNCACO type correlation experiments are an alternative for assignment of backbone resonances in extensively deuterated proteins in the solid-state, given the fact that line widths on the order of 14-17 Hz are achieved in the carbonyl dimension without the need of high power decoupling. The achieved resolution demonstrates that MAS solid-state NMR on extensively deuterated proteins is able to compete with solution-state NMR spectroscopy if proteins are investigated with correlation times tau(c) that exceed 25 ns. PMID:20232230

  10. Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions

    PubMed Central

    Weber, Daniela; Davies, Michael J.; Grune, Tilman

    2015-01-01

    Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples. PMID:26141921

  11. On the satisfaction of backbone‐carbonyl lone pairs of electrons in protein structures

    PubMed Central

    2016-01-01

    Abstract Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals’ interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone‐carbonyl oxygen atoms located within α‐helices and β‐sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone‐carbonyl oxygen atoms from a set of high‐resolution protein structures and associated molecular‐dynamics simulations in water. We included more‐recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα‐H bonds and methyl‐H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone‐carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α‐ and β‐structure. In addition, we find examples of under‐ and over‐satisfied carbonyl‐oxygen atoms, and we identify both sequence‐dependent and sequence‐independent secondary‐structural motifs in which these reside. Our analysis provides a more‐detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design. PMID:26833776

  12. The effect of occupational lead exposure on lipid peroxidation, protein carbonylation, and plasma viscosity.

    PubMed

    Kasperczyk, Sławomir; Słowińska-Łożyńska, Ludmiła; Kasperczyk, Aleksandra; Wielkoszyński, Tomasz; Birkner, Ewa

    2015-12-01

    The aim of the study was to investigate the influence of occupational lead (Pb) exposure on lipid peroxidation, protein carbonylation, and plasma viscosity in workers. The examined group included 283 healthy male employees of manufacturing facilities using zinc and Pb. The mean blood concentrations of Pb and zinc protoporphyrin as well as the mean urine δ-aminolevulinic acid levels were used as markers of exposure for the examined group. Taking into account the obtained mean values of blood lead level, the examined group was divided into three subgroups. When comparing the control group with the subgroups, Pb exposure markers were significantly elevated in all the three subgroups. Concentrations of conjugated dienes (CD), lipid hydroperoxides, malondialdehyde (MDA), and protein carbonyl groups were also significantly increased. Conversely, the levels of total protein and protein sulfhydryls were significantly decreased in the subgroups compared with the controls. The plasma viscosity was significantly elevated in the subgroups. A dose-response between Pb levels and plasma viscosity was not observed. Pb supposedly elevates MDA and CD in a dose-dependent manner. In conclusion, occupational Pb exposure induces oxidative stress that results in lipid and protein damage. Moreover, Pb-induced oxidative stress is likely the primary factor that elevates plasma viscosity, despite decreased protein levels.

  13. Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis.

    PubMed

    Bizzozero, Oscar A; DeJesus, Gisela; Callahan, Kelly; Pastuszyn, Andrzej

    2005-09-01

    Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). Increased levels of reactive oxygen species (ROS) derived from infiltrating macrophages and microglial cells have been shown to reduce the levels of endogenous antioxidants and to cause the oxidation of various substrates within the MS plaque. To determine whether oxidative damage takes place beyond visible MS plaques, the occurrence of total carbonyls (TCOs) and protein carbonyls (PCOs) in the normal-appearing white matter (NAWM) and gray matter (NAGM) of eight MS brains was assessed and compared with those of four control brains. The data show that most (7/8) of the MS-WM samples contain increased amounts of PCOs as determined by reaction with 2,4-dinitrophenylhydrazine and Western blot analysis. These samples also have high levels of glial fibrilary acidic protein (GFAP), suggesting that oxidative damage is related to the presence of small lesions. In contrast, we detected no evidence of protein thiolation (glutathionylation and cysteinylation) in the diseased tissue. To our surprise, MS-NAGM specimens with high GFAP content also showed three times the concentration of TCOs and PCOs as the controls. The increase in PCOs is likely to be a consequence of reduced levels of antioxidants, in that the concentration of nonprotein thiols in both MS-WM and -GM decreased by 30%. Overall, our data support the current view that both NAWM and -GM from MS brains contain considerable biochemical alterations. The involvement of GM in MS was also supported by the decrease in the levels of neurofilament light protein in all the specimens analyzed. To the best of our knowledge, this is the first study demonstrating the presence of increased protein carbonylation in post-mortem WM and GM tissue of MS patients.

  14. Time and dose effects of cigarette smoke and acrolein on protein carbonyl formation in HaCaT keratinocytes.

    PubMed

    Avezov, K; Reznick, A Z; Aizenbud, D

    2015-01-01

    Cigarette smoke (CS) is an important environmental source of human exposure to a highly toxic and chemically active α,β-unsaturated aldehyde: acrolein. It is capable of causing protein carbonylation and dysfunction, especially in oral tissues of smokers, constantly exposed to CS toxic constituents. The foremost damage is considered to be cumulative, but even a short exposure can be potentially harmful. The objectives of the current study were to examine the short time and dose effects of direct CS and acrolein exposure on intracellular protein carbonylation in epithelial cells. HaCaT-keratinocytes were exposed to different doses of acrolein and whole phase CS using a unique smoking simulator apparatus that mimics the exposure in smokers. The rate of intracellular protein carbonyl modification was examined 10-60 min after the exposure by Western blot. In addition, the effect of pre-incubation with a thiol scavenger N-acetylcysteine (NAC) was also assessed. We found that intracellular protein carbonyls increased as fast as 10 min after CS exposure and their concentration doubled after 20 min, with a slight elevation afterwards. Also, carbonyl levels increased gradually as CS and acrolein doses were elevated. Addition of 1 mM NAC neutralized part of the damage. We conclude that CS and acrolein intracellular protein carbonylation is dose- and time- dependent. Even a short time exposure to CS and its aldehydic constituents can be potentially harmful.

  15. Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

    PubMed Central

    Coughlan, Christina; Walker, Douglas I.; Lohr, Kelly M.; Richardson, Jason R.; Saba, Laura M.; Caudle, W. Michael; Fritz, Kristofer S.; Roede, James R.

    2015-01-01

    Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson's disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration. PMID:26345149

  16. Identification of oxidatively modified proteins in salt-stressed Arabidopsis: a carbonyl-targeted proteomics approach.

    PubMed

    Mano, Jun'ichi; Nagata, Mitsuaki; Okamura, Shoutarou; Shiraya, Takeshi; Mitsui, Toshiaki

    2014-07-01

    In plants, environmental stresses cause an increase in the intracellular level of reactive oxygen species (ROS), leading to tissue injury. To obtain biochemical insights into this damage process, we investigated the protein carbonyls formed by ROS or by the lipid peroxide-derived α,β-unsaturated aldehydes and ketones (i.e. reactive carbonyl species, or RCS) in the leaves of Arabidopsis thaliana under salt stress. A. thaliana Col-0 plants that we treated with 300 mM NaCl for 72 h under continuous illumination suffered irreversible leaf damage. Several RCS such as 4-hydroxy-(E)-2-nonenal (HNE) were increased within 12 h of this salt treatment. Immunoblotting using distinct antibodies against five different RCS, i.e. HNE, 4-hydroxy-(E)-2-hexenal, acrolein, crotonaldehyde and malondialdehyde, revealed that RCS-modified proteins accumulated in leaves with the progress of the salt stress treatment. The band pattern of Western blotting suggested that these different RCS targeted a common set of proteins. To identify the RCS targets, we collected HNE-modified proteins via an anti-HNE antiserum affinity trap and performed an isobaric tag for relative and absolute quantitation, as a quantitative proteomics approach. Seventeen types of protein, modified by 2-fold more in the stressed plants than in the non-stressed plants, were identified as sensitive RCS targets. With aldehyde-reactive probe-based affinity trapping, we collected the oxidized proteins and identified 22 additional types of protein as sensitive ROS targets. These RCS and ROS target proteins were distributed in the cytosol and apoplast, as well as in the ROS-generating organelles the peroxisome, chloroplast and mitochondrion, suggesting the participation of plasma membrane oxidation in the cellular injury. Possible mechanisms by which these modified targets cause cell death are discussed.

  17. Fish proteins as targets of ferrous-catalyzed oxidation: identification of protein carbonyls by fluorescent labeling on two-dimensional gels and MALDI-TOF/TOF mass spectrometry.

    PubMed

    Pazos, Manuel; da Rocha, Angela Pereira; Roepstorff, Peter; Rogowska-Wrzesinska, Adelina

    2011-07-27

    Protein oxidation in fish meat is considered to affect negatively the muscle texture. An important source of free radicals taking part in this process is Fenton's reaction dependent on ferrous ions present in the tissue. The aim of this study was to investigate the susceptibility of cod muscle proteins in sarcoplasmic and myofibril fractions to in vitro metal-catalyzed oxidation and to point out protein candidates that might play a major role in the deterioration of fish quality. Extracted control proteins and proteins subjected to free radicals generated by Fe(II)/ascorbate mixture were labeled with fluorescein-5-thiosemicarbazide (FTSC) to tag carbonyl groups and separated by two-dimensional gel electrophoresis. Consecutive visualization of protein carbonyl levels by capturing the FTSC signal and total protein levels by capturing the SyproRuby staining signal allowed us to quantify the relative change in protein carbonyl levels corrected for changes in protein content. Proteins were identified using MALDI-TOF/TOF mass spectrometry and homology-based searches. The results show that freshly extracted cod muscle proteins exhibit a detectable carbonylation background and that the incubation with Fe(II)/ascorbate triggers a further oxidation of both sarcoplasmic and myofibril proteins. Different proteins exhibited various degrees of sensitivity to oxidation processes. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), nucleoside diphosphate kinase B (NDK), triosephosphate isomerase, phosphoglycerate mutase, lactate dehydrogenase, creatine kinase, and enolase were the sarcoplasmic proteins most vulnerable to ferrous-catalyzed oxidation. Moreover, NDK, phosphoglycerate mutase, and GAPDH were identified in several spots differing by their pI, and those forms showed different susceptibilities to metal-catalyzed oxidation, indicating that post-translational modifications may change the resistance of proteins to oxidative damage. The Fe(II)/ascorbate treatment significantly

  18. Polysulfides protect SH-SY5Y cells from methylglyoxal-induced toxicity by suppressing protein carbonylation: A possible physiological scavenger for carbonyl stress in the brain.

    PubMed

    Koike, Shin; Kayama, Tasuku; Yamamoto, Shigeyoshi; Komine, Daisuke; Tanaka, Ryo; Nishimoto, Shoichi; Suzuki, Toshihiro; Kishida, Atsushi; Ogasawara, Yuki

    2016-07-01

    The formation of advanced glycation end products (AGEs) is associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease and schizophrenia. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is known to be a major precursor for AGEs in modified proteins. Thus, a scavenger of MG might provide beneficial effects by suppressing the accumulation of AGEs and the occurrence of diseases induced by carbonyl stress. Meanwhile, polysulfides, one of the typical bound sulfur species, are oxidized forms of hydrogen sulfide (H2S) and may play a variety of roles in the brain. Herein, we assessed the scavenging ability of polysulfides against neuronal carbonyl stress induced by MG. First, we showed that polysulfides could protect differentiated (df)-SH-SY5Y cells from MG-induced cytotoxicity. When cells were pretreated with polysulfides, MG-induced cytotoxicity was attenuated with a rapid decrease in intracellular MG levels. Moreover, we found that polysulfides significantly suppressed the formation of MG-modified proteins in df-SH-SY5Y cells. Although polysulfide treatment increased endogenous GSH levels in the neuronal cells, its effects on MG-induced cytotoxicity were not affected by GSH concentration. Our results demonstrated that polysulfides had the direct potentials to protect neuronal cells against MG separate to the enzymatic detoxification system that required GSH. PMID:27163164

  19. Proteomic profile of carbonylated proteins in rat liver: discovering possible mechanisms for tetracycline-induced steatosis.

    PubMed

    Deng, Zhenglu; Yan, Siyu; Hu, Hui; Duan, Zhigui; Yin, Lanxuan; Liao, Shenke; Sun, Yubai; Yin, Dazhong; Li, Guolin

    2015-01-01

    To investigate biochemical mechanisms for the tetracycline-induced steatosis in rats, targeted proteins of oxidative modification were profiled. The results showed that tetracycline induced lipid accumulation, oxidative stress, and cell viability decline in HepG2 cells only under the circumstances of palmitic acid overload. Tetracycline administration in rats led to significant decrement in blood lipids, while resulted in more than four times increment in intrahepatic triacylglycerol and typical microvesicular steatosis in the livers. The triacylglycerol levels were positively correlated with oxidative stress. Proteomic profiles of carbonylated proteins revealed 26 targeted proteins susceptible to oxidative modification and most of them located in mitochondria. Among them, the long-chain specific acyl-CoA dehydrogenase was one of the key enzymes regulating fatty acid β-oxidation. Oxidative modification of the enzyme in the tetracycline group depressed its enzymatic activity. In conclusion, the increased influx of lipid into the livers is the first hit of tetracycline-induced microvesicular steatosis. Oxidative stress is an essential part of the second hit, which may arise from the lipid overload and attack a series of functional proteins, aggravating the development of steatosis. The 26 targeted proteins revealed here provide a potential direct link between oxidative stress and tetracycline-induced steatosis.

  20. Effect of selenium and vitamin e supplementation on plasma protein carbonyl levels in patients with arsenic-related skin lesions.

    PubMed

    Mahata, Julie; Argos, Maria; Verret, Wendy; Kibriya, Muhammad G; Santella, Regina M; Ahsan, Habibul

    2008-01-01

    An estimated 35 million people in Bangladesh have been chronically exposed to arsenic in drinking water and are at risk of an array of adverse health conditions. The mechanisms of arsenic toxicity have not been well established; however, oxidative stress has been one commonly proposed pathway. In this study, we evaluated the effect of antioxidant supplementation on plasma protein oxidation among patients with arsenical skin lesions participating in a randomized double-blinded placebo-controlled trial of vitamin E and selenium. Subjects were randomized to 1 of 4 treatments arms (vitamin E, selenium, combination, or placebo) and were treated for a 6-mo period. We observed a dose-dependent increase in adjusted protein carbonyl levels by arsenic exposure status in the pretreatment samples, although trends were not statistically significant. Following the 6-mo intervention, there was a decrease in protein carbonyl levels in each treatment group, although no resultant decrease was significantly different from that seen in the placebo group. Although we did not see a notable effect of selenium or vitamin E supplementation on changes in protein carbonyl levels, these preliminary data demonstrate a feasible methodological approach for the assessment of plasma protein carbonyls in relation to environmental toxicants in a human population and their potential use as endpoints in intervention trials.

  1. Increased carbonyl protein level in the stratum corneum of inflammatory skin disorders: A non-invasive approach.

    PubMed

    Iwai, Ichiro; Shimadzu, Kiyo; Kobayashi, Yusuke; Hirao, Tetsuji; Etou, Takafumi

    2010-08-01

    The stratum corneum (SC) is the interface of body and environment, and is continuously exposed to oxidative stress, resulting in carbonyl modification of proteins. We have developed a simple and non-invasive method to assess carbonyl protein (CP) level in the SC, applied it to various kinds of skin, and revealed a link between the stratum corneum carbonylated protein (SCCP) level and water content in the SC. The purpose of the present study is to examine the SCCP level in inflammatory skin disorders associated with xerosis. Psoriasis vulgaris (PV) and atopic dermatitis (AD) are typical inflammatory skin disorders, of which the stratum corneum shows markedly low water content. SC samples were non-invasively collected from the lesional and non-lesional areas of PV and AD by adhesive tape stripping, and their carbonyl groups were determined by reaction with fluorescein-5-thiosemicarbazide. The average fluorescence intensity of the SC was calculated as SCCP level. Higher SCCP level was observed in the lesional area of PV as compared with non-lesional area or healthy control. Lesional area of AD also exhibited higher SCCP level than corresponding non-lesional area, of which SCCP level was slightly higher than the healthy control. These data suggest the involvement of oxidative modification of the SC protein, at least in part, in generation of xerotic skin in inflammatory skin disorders as well as dry skin in healthy subjects.

  2. Impact of trolox, quercetin, genistein and gallic acid on the oxidative damage to myofibrillar proteins: the carbonylation pathway.

    PubMed

    Utrera, Mariana; Estévez, Mario

    2013-12-15

    The carbonylation pathway involves the oxidative deamination of lysine residues to yield a carbonyl compound (α-aminoadipic semialdehyde) that can be further oxidised to α-aminoadipic acid and form Schiff bases structures. The effect of trolox and other phenolic compounds (PhC) (namely genistein, quercetin and gallic acid) on the protein carbonylation pathway occurred during the oxidation of myofibrillar proteins (MP) catalysed by a Fe(3+)/H2O2 system was studied. Trolox and PhC can exert either antioxidant or pro-oxidant capacities depending on their concentration, the oxidation conditions and the target in proteins. In general, quercetin and genistein showed an antioxidant activity towards lipid oxidation and the carbonylation pathway at different concentrations under the analysed conditions. Plausible mechanisms for the antioxidant and pro-oxidant effects of trolox and PhC on MP are discussed. Further research is needed to shed light on the effect of PhC mixtures on both lipid and protein oxidation. PMID:23993577

  3. Protein carbonylation and water-holding capacity of pork subjected to frozen storage: effect of muscle type, premincing, and packaging.

    PubMed

    Estévez, Mario; Ventanas, Sonia; Heinonen, Marina; Puolanne, Eero

    2011-05-25

    The present work aimed to study the relationship between protein carbonylation and the loss of water-holding capacity (WHC) occurring during frozen storage of porcine muscles. Pork samples corresponding to two different muscle types, glycolytic M. longissimus dorsi (LD) and oxidative M. psoas major (PM), and subjected to two different premincing, minced (MINCED) and intact pork pieces (INTACT), and packaging, vacuum packaged (VACUUM) and packed in oxygen-permeable bags (OXYGEN), procedures were frozen (-18 °C/12 weeks) and analyzed at sampling times upon thawing (weeks 1, 4, 8, and 12) for the relative amount of specific protein carbonyls, α-aminoadipic and γ-glutamic semialdehydes (AAS and GGS, respectively), and their ability to hold water using two different techniques. The formation of protein carbonyls occurred concomitantly with the loss of WHC, and both phenomena were found to be more intense in LD muscles and in MINCED and OXYGEN pork samples. The loss in WHC was from ca. 10 to 30% in 12 weeks, depending on the method of determination. Plausible mechanisms by which protein carbonylation may decrease the WHC of pork samples are thoroughly discussed in the present paper. Besides the likely impact of protein carbonylation in the water-myofibrillar protein relationships, the implication of AAS and GGS in further reactions including plausible cross-linking would explain the decrease of these semialdehydes by the end of frozen storage and would reinforce their liability in the loss of WHC of porcine muscles. The exact nature of these reactions, however, should be investigated in further studies.

  4. Trivalent arsenicals induce lipid peroxidation, protein carbonylation, and oxidative DNA damage in human urothelial cells.

    PubMed

    Wang, Tsing-Cheng; Jan, Kun-Yan; Wang, Alexander S S; Gurr, Jia-Ran

    2007-02-01

    Drinking arsenic-contaminated water is associated with an increased risk of bladder cancer. Arsenate (iAs(V)), arsenite (iAs(III)), monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)), dimethylarsinous acid (DMA(III)), and dimethylarsinic acid (DMA(V)) have all been detected in the urine of people who drink arsenic-contaminated water. The aim of this research was to investigate which of these arsenicals are more hazardous to human urothelial cells. The results indicate that iAs(III), MMA(III), and DMA(III) were more potent in inducing cytotoxicity, lipid peroxidation, protein carbonylation, oxidative DNA damage, nitric oxide, superoxide, hydrogen peroxide, and cellular free iron than MMA(V), DMA(V), and iAs(V) in human urothelial carcinoma and transformed cells. However, the results did not show convincingly that the trivalent arsenicals were more potent than pentavalent arsenicals in decreasing the intracellular contents of total thiol, protein thiol, and reduced glutathione. Induction of oxidative DNA damage was observed with 0.2 microM of iAs(III), MMA(III), or DMA(III) as early as 1h. Because of its high oxidative damage, higher proportion in urine, and lower cytotoxicity, DMA(III) may be the most hazardous arsenical to human urothelial cells.

  5. Protein carbonyl levels correlate with performance in elite field hockey players.

    PubMed

    Rosa-Lima, Frederico Luis; Lannes, Luiz; Viana-Gomes, Diego; Pierucci, Anna Paola T R; Salerno, Verônica P

    2015-07-01

    Excess and incorrectly selected exercise can degrade athletic performance from an imbalance in redox homeostasis and oxidative stress, but well-planned training and nutrition can improve antioxidant capacity. The aim of the study was to investigate how nutrient intake could influence oxidative stress and cell lesion biomarkers after 5 days of training followed by a game. Blood was collected from 10 athletes at the start of training (basal), after training (pre-game), and postgame. Their acceleration capacity also was measured pre- and postgame. Blood analysis showed an increase in lactate concentration postgame (13%) and total antioxidant capacity increased both pre-game (13.1%) and postgame (12.7%), all in comparison with basal levels. An oxidative stress marker, protein carbonyl (PC), increased 3-fold over the course of the game, which correlated with a decreased acceleration (r = 0.749). For biomarkers of tissue damage, creatine kinase and aspartate transaminase (AST) increased postgame by 150% and 75%, respectively. The AST variation had a high negative correlation with energy and carbohydrate consumption and a moderate correlation with lipid and vitamin C intake. Protein intake had a positive but moderate correlation with reduced glutathione. The observed correlations suggest that nutritional monitoring can improve exercise physiological homeostasis and that PC serves as a good biomarker for oxidative stress and performance loss. PMID:25962716

  6. Protein carbonyl levels correlate with performance in elite field hockey players.

    PubMed

    Rosa-Lima, Frederico Luis; Lannes, Luiz; Viana-Gomes, Diego; Pierucci, Anna Paola T R; Salerno, Verônica P

    2015-07-01

    Excess and incorrectly selected exercise can degrade athletic performance from an imbalance in redox homeostasis and oxidative stress, but well-planned training and nutrition can improve antioxidant capacity. The aim of the study was to investigate how nutrient intake could influence oxidative stress and cell lesion biomarkers after 5 days of training followed by a game. Blood was collected from 10 athletes at the start of training (basal), after training (pre-game), and postgame. Their acceleration capacity also was measured pre- and postgame. Blood analysis showed an increase in lactate concentration postgame (13%) and total antioxidant capacity increased both pre-game (13.1%) and postgame (12.7%), all in comparison with basal levels. An oxidative stress marker, protein carbonyl (PC), increased 3-fold over the course of the game, which correlated with a decreased acceleration (r = 0.749). For biomarkers of tissue damage, creatine kinase and aspartate transaminase (AST) increased postgame by 150% and 75%, respectively. The AST variation had a high negative correlation with energy and carbohydrate consumption and a moderate correlation with lipid and vitamin C intake. Protein intake had a positive but moderate correlation with reduced glutathione. The observed correlations suggest that nutritional monitoring can improve exercise physiological homeostasis and that PC serves as a good biomarker for oxidative stress and performance loss.

  7. Direct 13C-detection for carbonyl relaxation studies of protein dynamics.

    PubMed

    Pasat, Gabriela; Zintsmaster, John S; Peng, Jeffrey W

    2008-08-01

    We describe a method that uses direct 13C-detection for measuring rotating-frame carbonyl (13CO) relaxation rates to describe protein functional dynamics. Key advantages of method include the following: (i) unique access to 13CO groups that lack a scalar-coupled 15N-1H group; (ii) insensitivity to 15N/1H exchange-broadening that can derail 1H-detected 15N and HNCO methods; (iii) avoidance of artifacts caused by incomplete water suppression. We demonstrate the approach for both backbone and side-chain 13CO groups. Accuracy of the 13C-detected results is supported by their agreement with those obtained from established HNCO-based approaches. Critically, we show that the 13C-detection approach provides access to the 13CO groups of functionally important residues that are invisible via 1H-detected HNCO methods because of exchange-broadening. Hence, the 13C-based method fills gaps inherent in canonical 1H-detected relaxation experiments, and thus provides a novel complementary tool for NMR studies of biomolecular flexibility. PMID:18514001

  8. Redox Proteomic Profiling of Specifically Carbonylated Proteins in the Serum of Triple Transgenic Alzheimer’s Disease Mice

    PubMed Central

    Shen, Liming; Chen, Youjiao; Yang, Aochu; Chen, Cheng; Liao, Liping; Li, Shuiming; Ying, Ming; Tian, Jing; Liu, Qiong; Ni, Jiazuan

    2016-01-01

    Oxidative stress is a key event in the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD). To investigate the role of oxidative stress in AD and to search for potential biomarkers in peripheral blood, serums were collected in this study from the 3-, 6-, and 12-month-old triple transgenic AD mice (3×Tg-AD mice) and the age- and sex-matched non-transgenic (non-Tg) littermates. The serum oxidized proteins were quantified by slot-blot analysis and enzyme-linked immunosorbent assay (ELISA) to investigate the total levels of serum protein carbonyl groups. Western blotting, in conjunction with two-dimensional gel electrophoresis (2D-Oxyblot), was employed to identify and quantify the specifically-carbonylated proteins in the serum of 3×Tg-AD mice. The results showed that the levels of serum protein carbonyls were increased in the three month old 3×Tg-AD mice compared with the non-Tg control mice, whereas no significant differences were observed in the six and 12 months old AD mice, suggesting that oxidative stress is an early event in AD progression. With the application of 2D-Oxyblot analysis, (immunoglobin) Ig gamma-2B chain C region (IGH-3), Ig lambda-2 chain C region (IGLC2), Ig kappa chain C region (IGKC), and Ig kappa chain V-V region HP R16.7 were identified as significantly oxidized proteins compared with the control. Among them IGH-3 and IGKC were validated via immunoprecipitation and Western blot analysis. Identification of oxidized proteins in the serums of 3×Tg-AD mice can not only reveal potential roles of those proteins in the pathogenesis of AD but also provide potential biomarkers of AD at the early stage. PMID:27077851

  9. Long-lived crowded-litter mice have an age-dependent increase in protein synthesis to DNA synthesis ratio and mTORC1 substrate phosphorylation.

    PubMed

    Drake, Joshua C; Bruns, Danielle R; Peelor, Frederick F; Biela, Laurie M; Miller, Richard A; Hamilton, Karyn L; Miller, Benjamin F

    2014-11-01

    Increasing mouse litter size [crowded litter (CL)] presumably imposes a transient nutrient stress during suckling and extends lifespan through unknown mechanisms. Chronic calorically restricted and rapamycin-treated mice have decreased DNA synthesis and mTOR complex 1 (mTORC1) signaling but maintained protein synthesis, suggesting maintenance of existing cellular structures. We hypothesized that CL would exhibit similar synthetic and signaling responses to other long-lived models and, by comparing synthesis of new protein to new DNA, that insight may be gained into the potential preservation of existing cellular structures in the CL model. Protein and DNA synthesis was assessed in gastroc complex, heart, and liver of 4- and 7-mo CL mice. We also examined mTORC1 signaling in 3- and 7-mo aged animals. Compared with controls, 4-mo CL had greater DNA synthesis in gastroc complex with no differences in protein synthesis or mTORC1 substrate phosphorylation across tissues. Seven-month CL had less DNA synthesis than controls in heart and greater protein synthesis and mTORC1 substrate phosphorylation across tissues. The increased new protein-to-new DNA synthesis ratio suggests that new proteins are synthesized more so in existing cells at 7 mo, differing from 4 mo, in CL vs. controls. We propose that, in CL, protein synthesis shifts from being directed toward new cells (4 mo) to maintenance of existing cellular structures (7 mo), independently of decreased mTORC1.

  10. Nitric Oxide Enhances Desiccation Tolerance of Recalcitrant Antiaris toxicaria Seeds via Protein S-Nitrosylation and Carbonylation

    PubMed Central

    Bai, Xuegui; Yang, Liming; Tian, Meihua; Chen, Jinhui; Shi, Jisen; Yang, Yongping; Hu, Xiangyang

    2011-01-01

    The viability of recalcitrant seeds is lost following stress from either drying or freezing. Reactive oxygen species (ROS) resulting from uncontrolled metabolic activity are likely responsible for seed sensitivity to drying. Nitric oxide (NO) and the ascorbate-glutathione cycle can be used for the detoxification of ROS, but their roles in the seed response to desiccation remain poorly understood. Here, we report that desiccation induces rapid accumulation of H2O2, which blocks recalcitrant Antiaris toxicaria seed germination; however, pretreatment with NO increases the activity of antioxidant ascorbate-glutathione pathway enzymes and metabolites, diminishes H2O2 production and assuages the inhibitory effects of desiccation on seed germination. Desiccation increases the protein carbonylation levels and reduces protein S-nitrosylation of these antioxidant enzymes; these effects can be reversed with NO treatment. Antioxidant protein S-nitrosylation levels can be further increased by the application of S-nitrosoglutathione reductase inhibitors, which further enhances NO-induced seed germination rates after desiccation and reduces desiccation-induced H2O2 accumulation. These findings suggest that NO reinforces recalcitrant seed desiccation tolerance by regulating antioxidant enzyme activities to stabilize H2O2 accumulation at an appropriate concentration. During this process, protein carbonylation and S-nitrosylation patterns are used as a specific molecular switch to control antioxidant enzyme activities. PMID:21674063

  11. Cross-correlation between a carbonyl C' chemical shift anisotropy and a long-range dipolar C'HA coupling in proteins using symmetrical reconversion.

    PubMed

    Loth, Karine; Pelupessy, Philippe; Bodenhausen, Geoffrey

    2003-10-01

    A new sequence is described to measure the cross-correlation rates between the chemical shift anisotropy of the carbonyl carbon-13 nucleus and the dipole-dipole interaction between this carbonyl and the alpha-proton in proteins. The sequence is based on the symmetrical reconversion principle and is insensitive to experimental errors and to violations of the secular approximation. The cross-correlation rate depends on the backbone angle psi. The advantages and limitations of the sequence are discussed.

  12. Age-dependent increase of brain copper levels and expressions of copper regulatory proteins in the subventricular zone and choroid plexus

    PubMed Central

    Fu, Sherleen; Jiang, Wendy; Zheng, Wei

    2015-01-01

    Our recent data suggest a high accumulation of copper (Cu) in the subventricular zone (SVZ) along the wall of brain ventricles. Anatomically, SVZ is in direct contact with cerebrospinal fluid (CSF), which is secreted by a neighboring tissue choroid plexus (CP). Changes in Cu regulatory gene expressions in the SVZ and CP as the function of aging may determine Cu levels in the CSF and SVZ. This study was designed to investigate the associations between age, Cu levels, and Cu regulatory genes in SVZ and plexus. The SVZ and CP were dissected from brains of 3-week, 10-week, or 9-month old male rats. Analyses by atomic absorption spectroscopy revealed that the SVZ of adult and old animals contained the highest Cu level compared with other tested brain regions. Significantly positive correlations between age and Cu levels in SVZ and plexus were observed; the SVZ Cu level of old animals was 7.5- and 5.8-fold higher than those of young and adult rats (p < 0.01), respectively. Quantitation by qPCR of the transcriptional expressions of Cu regulatory proteins showed that the SVZ expressed the highest level of Cu storage protein metallothioneins (MTs), while the CP expressed the high level of Cu transporter protein Ctr1. Noticeably, Cu levels in the SVZ were positively associated with type B slow proliferating cell marker Gfap (p < 0.05), but inversely associated with type A proliferating neuroblast marker Dcx (p < 0.05) and type C transit amplifying progenitor marker Nestin (p < 0.01). Dmt1 had significant positive correlations with age and Cu levels in the plexus (p < 0.01). These findings suggest that Cu levels in all tested brain regions are increased as the function of age. The SVZ shows a different expression pattern of Cu-regulatory genes from the CP. The age-related increase of MTs and decrease of Ctr1 may contribute to the high Cu level in this neurogenesis active brain region. PMID:26106293

  13. Age-dependent alterations of c-fos and growth regulation in human fibroblasts expressing the HPV16 E6 protein.

    PubMed Central

    Yan, Y; Ouellette, M M; Shay, J W; Wright, W E

    1996-01-01

    Normal human cells in culture become senescent after a limited number of population doublings. Senescent cells display characteristic changes in gene expression, among which is a repression of the ability to induce the c-fos gene. We have proposed a two-stage model for cellular senescence in which the mortality stage 1 (M1) mechanism can be overcome by agents that bind both the product of the retinoblastoma susceptibility gene (pRB)-like pocket proteins and p53. In this study we determined whether the repression of c-fos at M1 was downstream of the p53 or pRB-like "arms" of the M1 mechanism. We examined c-fos expression during the entire lifespan of normal human fibroblasts carrying E6 (which binds p53), E7 (which binds pRB), or both E6 and E7 of human papilloma virus type 16. The results indicate a dramatic change in cellular physiology at M1. Before M1, c-fos inducibility is controlled by an E6-independent mechanism that is blocked by E7. After M1, c-fos inducibility becomes dependent on E6 whereas E7 has no effect. In addition, a novel oscillation of c-fos expression with an approximately 2-h periodicity appears in E6-expressing fibroblasts post-M1. Accompanying this shift at M1 is a dramatic change in the ability to divide in low serum. Before M1, E6-expressing fibroblasts growth arrest in 0.3% serum, although they continue dividing under those conditions post-M1. These results demonstrate the unique physiology of fibroblasts during the extended lifespan between M1 and M2 and suggest that p53 might participate in the process that represses the c-fos gene at the onset of cellular senescence. Images PMID:8817002

  14. iCar-PseCp: identify carbonylation sites in proteins by Monte Carlo sampling and incorporating sequence coupled effects into general PseAAC

    PubMed Central

    Jia, Jianhua; Liu, Zi; Xiao, Xuan; Liu, Bingxiang; Chou, Kuo-Chen

    2016-01-01

    Carbonylation is a posttranslational modification (PTM or PTLM), where a carbonyl group is added to lysine (K), proline (P), arginine (R), and threonine (T) residue of a protein molecule. Carbonylation plays an important role in orchestrating various biological processes but it is also associated with many diseases such as diabetes, chronic lung disease, Parkinson's disease, Alzheimer's disease, chronic renal failure, and sepsis. Therefore, from the angles of both basic research and drug development, we are facing a challenging problem: for an uncharacterized protein sequence containing many residues of K, P, R, or T, which ones can be carbonylated, and which ones cannot? To address this problem, we have developed a predictor called iCar-PseCp by incorporating the sequence-coupled information into the general pseudo amino acid composition, and balancing out skewed training dataset by Monte Carlo sampling to expand positive subset. Rigorous target cross-validations on a same set of carbonylation-known proteins indicated that the new predictor remarkably outperformed its existing counterparts. For the convenience of most experimental scientists, a user-friendly web-server for iCar-PseCp has been established at http://www.jci-bioinfo.cn/iCar-PseCp, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved. It has not escaped our notice that the formulation and approach presented here can also be used to analyze many other problems in computational proteomics. PMID:27153555

  15. Use of fluorescein hydrazide and fluorescein thiosemicarbazide reagents for the fluorometric determination of protein carbonyl groups and for the detection of oxidized protein on polyacrylamide gels.

    PubMed

    Ahn, B; Rhee, S G; Stadtman, E R

    1987-03-01

    Highly fluorescent thiosemicarbazide and hydrazide prepared by reaction of fluorescein isothiocyanate with hydrazine or adipic acid dihydrazide have been used to monitor the presence of carbonyl groups in oxidatively modified proteins. After oxidation, proteins react with these reagents under anaerobic conditions in the dark to yield fluorescent protein conjugates (presumably thiosemicarbazones or hydrazones) which can be visualized as fluorescent bands following electrophoresis (0-4 degrees C) on lithium dodecyl sulfate-polyacrylamide gels. These reagents do not react with unoxidized proteins. The conjugates formed dissociate readily at room temperature but are fairly stable at pH 6-9, 0 degrees C. Current data suggest that these reagents will be useful in the detection and quantitation of oxidatively modified proteins in biological systems. PMID:2883911

  16. A NMR experiment for simultaneous correlations of valine and leucine/isoleucine methyls with carbonyl chemical shifts in proteins.

    PubMed

    Tugarinov, Vitali; Venditti, Vincenzo; Marius Clore, G

    2014-01-01

    A methyl-detected 'out-and-back' NMR experiment for obtaining simultaneous correlations of methyl resonances of valine and isoleucine/leucine residues with backbone carbonyl chemical shifts, SIM-HMCM(CGCBCA)CO, is described. The developed pulse-scheme serves the purpose of convenience in recording a single data set for all Ile(δ1), Leu(δ) and Val(γ) (ILV) methyl positions instead of acquiring two separate spectra selective for valine or leucine/isoleucine residues. The SIM-HMCM(CGCBCA)CO experiment can be used for ILV methyl assignments in moderately sized protein systems (up to ~100 kDa) where the backbone chemical shifts of (13)C(α), (13)Cβ and (13)CO are known from prior NMR studies and where some losses in sensitivity can be tolerated for the sake of an overall reduction in NMR acquisition time.

  17. Nickel carbonyl

    Integrated Risk Information System (IRIS)

    Nickel carbonyl ; CASRN 13463 - 39 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  18. Carbonyl sulfide

    Integrated Risk Information System (IRIS)

    Carbonyl sulfide ; CASRN 463 - 58 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  19. Roux-en-Y Gastric Bypass Acutely Decreases Protein Carbonylation and Increases Expression of Mitochondrial Biogenesis Genes in Subcutaneous Adipose Tissue

    PubMed Central

    Jahansouz, Cyrus; Serrot, Federico J.; Frohnert, Brigitte I.; Foncea, Rocio E.; Dorman, Robert B.; Slusarek, Bridget; Leslie, Daniel B.; Bernlohr, David A.; Ikramuddin, Sayeed

    2015-01-01

    Background Mitochondrial dysfunction in adipose tissue has been implicated as a pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose tissue, chronic nutrient overload results in mitochondria driven increased reactive oxygen species (ROS) leading to carbonylation of proteins that impair mitochondrial function and downregulation of key genes linked to mitochondrial biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads to improvements in glycemic profile prior to significant weight loss. Consequently, we hypothesized that improved glycemia early after RYGB would be paralleled by decreased protein carbonylation and increased expression of genes related to mitochondrial biogenesis in adipose tissue. Methods To evaluate this hypothesis, 16 obese individuals were studied before and 7–8 days following RYGB and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained pre- and post-bariatric surgery as well as from eight healthy, non-obese individual controls. Results Prior to surgery, adipose tissue expression of PGC1α, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower expression in the obese bariatric surgery group when compared to lean controls (p<0.05). Following RYGB, but not after AGB, patients showed significant decrease in HOMA-IR, reduction in adipose protein carbonylation, and increased expression of genes linked to mitochondrial biogenesis. Conclusions These results suggest that rapid reduction in protein carbonylation and increased mitochondrial biogenesis may explain postoperative metabolic improvements following RYGB. PMID:25975200

  20. Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species

    PubMed Central

    Chung, Woon-Gye; Miranda, Cristobal L.; Stevens, Jan F.; Maier, Claudia S.

    2009-01-01

    Proanthocyanidins (PCs) have been shown to suppress the growth of diverse human cancer cells and are considered as promising additions to the arsenal of chemopreventive phytochemicals. An oligomeric mixture of PCs from hops (Humulus lupulus) significantly decreased cell viability of human colon cancer HT-29 cells in a dose-dependent manner. Hop PCs, at 50 or 100 μg/ml, exhibited apoptosis-inducing properties as shown by the increase in caspase-3 activity. Increased levels of intracellular reactive oxygen species (ROS) was accompanied by an augmented accumulation of protein carbonyls. Mass spectrometry-based proteomic analysis in combination with 2-alkenal-specific immunochemical detection identified β-actin and protein disulfide isomerase as major putative targets of acrolein adduction. Incubation of HT-29 cells with hop PCs resulted in morphological changes that indicated disruption of the actin cytoskeleton. PC-mediated hydrogen peroxide (H2O2) formation in the cell culture media was also quantified; but, the measured H2O2 levels would not explain the observed changes in the oxidative modifications of actin. These findings suggest new modes of action for proanthocyandins as antitumorgenic agents in human colon cancer cells, namely, promotion of protein oxidative modifications and cytoskeleton derangement. PMID:19271284

  1. Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels

    SciTech Connect

    Zhong, Linlin; Liu, Ziwen; Yan, Ruilan; Johnson, Stephen; Zhao, Yupei; Fang, Xiubin; Cao, Deliang

    2009-09-18

    Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 {mu}M, 4-hydroxynonenal (HNE) at 0.10 {mu}M, trans-2-hexanal at 0.10 {mu}M, and trans-2,4-hexadienal at 0.05 {mu}M, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 {mu}M (toxic) by converting to 1,4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.

  2. Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction.

    PubMed

    Hyzewicz, Janek; Tanihata, Jun; Kuraoka, Mutsuki; Ito, Naoki; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2015-05-01

    High intensity training induces muscle damage in dystrophin-deficient mdx mice, an animal model for Duchenne muscular dystrophy. However, low intensity training (LIT) rescues the mdx phenotype and even reduces the level of protein carbonylation, a marker of oxidative damage. Until now, beneficial effects of LIT were mainly assessed at the physiological level. We investigated the effects of LIT at the molecular level on 8-week-old wild-type and mdx muscle using 2D Western blot and protein-protein interaction analysis. We found that the fast isoforms of troponin T and myosin binding protein C as well as glycogen phosphorylase were overcarbonylated and downregulated in mdx muscle. Some of the mitochondrial enzymes of the citric acid cycle were overcarbonylated, whereas some proteins of the respiratory chain were downregulated. Of functional importance, ATP synthase was only partially assembled, as revealed by Blue Native PAGE analysis. LIT decreased the carbonylation level and increased the expression of fast isoforms of troponin T and of myosin binding protein C, and glycogen phosphorylase. In addition, it increased the expression of aconitate hydratase and NADH dehydrogenase, and fully restored the ATP synthase complex. Our study demonstrates that the benefits of LIT are associated with lowered oxidative damage as revealed by carbonylation and higher expression of proteins involved in energy metabolism and muscle contraction. Potentially, these results will help to design therapies for DMD based on exercise mimicking drugs. PMID:25660994

  3. Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction.

    PubMed

    Hyzewicz, Janek; Tanihata, Jun; Kuraoka, Mutsuki; Ito, Naoki; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2015-05-01

    High intensity training induces muscle damage in dystrophin-deficient mdx mice, an animal model for Duchenne muscular dystrophy. However, low intensity training (LIT) rescues the mdx phenotype and even reduces the level of protein carbonylation, a marker of oxidative damage. Until now, beneficial effects of LIT were mainly assessed at the physiological level. We investigated the effects of LIT at the molecular level on 8-week-old wild-type and mdx muscle using 2D Western blot and protein-protein interaction analysis. We found that the fast isoforms of troponin T and myosin binding protein C as well as glycogen phosphorylase were overcarbonylated and downregulated in mdx muscle. Some of the mitochondrial enzymes of the citric acid cycle were overcarbonylated, whereas some proteins of the respiratory chain were downregulated. Of functional importance, ATP synthase was only partially assembled, as revealed by Blue Native PAGE analysis. LIT decreased the carbonylation level and increased the expression of fast isoforms of troponin T and of myosin binding protein C, and glycogen phosphorylase. In addition, it increased the expression of aconitate hydratase and NADH dehydrogenase, and fully restored the ATP synthase complex. Our study demonstrates that the benefits of LIT are associated with lowered oxidative damage as revealed by carbonylation and higher expression of proteins involved in energy metabolism and muscle contraction. Potentially, these results will help to design therapies for DMD based on exercise mimicking drugs.

  4. Investigation into the Effects of Boron on Liver Tissue Protein Carbonyl, MDA, and Glutathione Levels in Endotoxemia.

    PubMed

    Balabanlı, Barbaros; Balaban, Tuba

    2015-10-01

    Endotoxin has been known to cause the formation and damage of free radical. The importance of boron for human life is increasing each passing day, and its consuming fields are continuing to expand due to the advances in science and technology. Therefore, in our study, we intended to investigate into the effects of boron on liver tissue oxidative events. Eighteen male Wistar albino rats were randomly separated into three equal groups in the experiments; control group, boron + endotoxin group, and endotoxin group. Dissolved in distilled water, boric acid (100 mg/kg) was administered to boron + endotoxin group via gavage procedure for 28 days. Only distilled water was administered to control and endotoxin groups via gavage procedure for 28 days. Then 4 mg/kg endotoxin (LPS; Escherichia coli 0111:B4) was intraperitoneally (ip) administered to boron + endotoxin and endotoxin groups on the 28th day. Sterile saline was injected into control group on the 28th day (ip). Malondialdehyde (MDA), which is the end product of lipid peroxidation in liver tissues, protein carbonyl compounds (PC), which are protein oxidization markers, and glutathione (GSH) levels were measured spectrophotometrically. The results were compared with Mann-Whitney U test. When boron + endotoxin group is compared with endotoxin group, PC levels of endotoxin group showed a significant increase. When GSH levels are compared, GSH level in boron + endotoxin group decreased according to endotoxin group. Variations among all groups in MDA levels were found to be statistically insignificant. We are of the opinion that endotoxin affects the proteins by forming free radicals, and boron may also cause the structural and/or functional changes in proteins in order to protect proteins from oxidization.

  5. Malondialdehyde, carbonyl proteins and albumin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Greilberger, J; Koidl, C; Greilberger, M; Lamprecht, M; Schroecksnadel, K; Leblhuber, F; Fuchs, D; Oettl, K

    2008-07-01

    The question arises as to whether oxidative stress has a primary role in neurodegeneration or is a secondary end-stage epiphenomenon. The aim of the present study was to determine oxidative stress parameters like malondialdehyde (MDA), carbonyl proteins (CP) and Albumin-disulphide (Alb-SSR) and relate these parameters to the immune parameter neopterin, folic acid and vitamin B12 as vitamins and homocysteine in patients with neuro-degenerative diseases (NDD), namely mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to an aged matched control group. MDA, CP and Alb-SSR were significantly increased in the NDD group compared to controls, but not vitamin B12, folic acid and neopterin. Significant correlations were found between CP and Alb-SSR, CP and MDA and between MDA and Alb-SSR including patients with NDD and the control group. These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.

  6. Carbonyl stress and schizophrenia.

    PubMed

    Arai, Makoto; Miyashita, Mitsuhiro; Kobori, Akiko; Toriumi, Kazuya; Horiuchi, Yasue; Itokawa, Masanari

    2014-09-01

    Appropriate biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with schizophrenia. Despite extensive efforts to clarify the underlying disease mechanisms, the main cause and pathophysiology of schizophrenia remain unclear. This is due in large part to disease heterogeneity, which results in biochemical differences within a single disease entity. Other factors include variability across clinical symptoms and disease course, along with varied risk factors and treatment responses. Although schizophrenia's positive symptoms are largely managed through treatment with atypical antipsychotics, new classes of drugs are needed to address the unmet medical need for improving cognitive dysfunction and promoting recovery of negative symptoms in these patients. Accumulation of toxic reactive dicarbonyls, such as methylglyoxal, are typical indicators of carbonyl stress, and result in the modification of proteins and the formation of advanced glycation end products, such as pentosidine. In June 2010, we reported on idiopathic carbonyl stress in a subpopulation of schizophrenia patients, leading to a failure of metabolic systems with plasma pentosidine accumulation and serum pyridoxal depletion. Our findings suggest two markers, pentosidine and pyridoxal, as beneficial for distinguishing a specific subgroup of schizophrenics. We believe that this information, derived from in vitro and in vivo studies, is beneficial in the search for personalized and hopefully more effective treatment regimens in schizophrenia. Here, we define a subtype of schizophrenia based on carbonyl stress and the potential for using carbonyl stress as a biomarker in the challenge of overcoming heterogeneity in schizophrenia treatment. PMID:24995521

  7. Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

    PubMed Central

    2014-01-01

    Background We examined if a purported anti-inflammatory supplement (AF) abrogated Western-diet (WD)-induced liver pathology in rats. AF contained: 1) protein concentrates from bovine colostrum and avian egg yolk; 2) herbal adaptogens and antioxidants; and 3) acetyl-L-carnitine. Methods Nine month-old male Brown Norway rats were allowed ad libitum access to WD for 41–43 days and randomly assigned to WD + AF feeding twice daily for the last 31–33 days (n = 8), or WD and water-placebo feeding twice daily for the last 31–33 days (n = 8). Rats fed a low-fat/low-sucrose diet (CTL, n = 6) for 41–43 days and administered a water-placebo twice daily for the last 31–33 days were also studied. Twenty-four hours following the last gavage-feed, liver samples were analyzed for: a) select mRNAs (via RT-PCR) as well as genome-wide mRNA expression patterns (via RNA-seq); b) lipid deposition; and, c) protein carbonyl and total antioxidant capacity (TAC). Serum was also examined for TAC, 8-isoprostane and clinical chemistry markers. Results WD + AF rats experienced a reduction in liver Tnf-α mRNA (-2.8-fold, p < 0.01). Serum and liver TAC was lower in WD + AF versus WD and CTL rats (p < 0.05), likely due to exogenous antioxidant ingredients provided through AF as evidenced by a tendency for mitochondrial SOD2 mRNA to increase in WD + AF versus CTL rats (p = 0.07). Liver fat deposition nor liver protein carbonyl content differed between WD + AF versus WD rats, although liver protein carbonyls tended to be lower in WD + AF versus CTL rats (p = 0.08). RNA-seq revealed that 19 liver mRNAs differed between WD + AF versus WD when both groups were compared with CTL rats (+/- 1.5-fold, p < 0.01). Bioinformatics suggest that AF prevented WD-induced alterations in select genes related to the transport and metabolism of carbohydrates in favor of select genes related to lipid transport and metabolism. Finally, serum clinical

  8. Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections

    PubMed Central

    Niloofa, Roshan; Rodrigo, Chaturaka; Karunanayake, Lilani; de Silva, H. Janaka; Wickremesinghe, A. R.; Premawansa, Sunil; Rajapakse, Senaka; Handunnetti, Shiroma M.

    2016-01-01

    Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to

  9. Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections.

    PubMed

    Fernando, Narmada; Wickremesinghe, Shalini; Niloofa, Roshan; Rodrigo, Chaturaka; Karunanayake, Lilani; de Silva, H Janaka; Wickremesinghe, A R; Premawansa, Sunil; Rajapakse, Senaka; Handunnetti, Shiroma M

    2016-01-01

    Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to

  10. Effect of sodium chloride and nitroprusside on protein carbonyl groups content and antioxidant enzyme activity in leaves of corn seedlings Zea mays L.

    PubMed

    Vasylyk, Yu V; Semchuk, N M; Lushchak, Ok V; Lushchak, V I

    2012-01-01

    The effect of sodium nitroprusside (SNP) and sodium chloride (NaCl) on protein carbonyl group content and activity of antioxidant enzymes was investigated in leaves of maize seedlings. Incubation with NaCl and SNP+NaCl increased the content of carbonyl proteins after 24 h. Treatment with SNP+NaCl during 48 h showed lower and after 72 h higher carbonyl protein content than that in the control. Catalase activity was higher in the leaves of SNP+NaCl-treated than in the leaves of SNP-treated seedlings after 24 h. Ascorbate peroxidase activity increased after incubation with 0.2 mM SNP for 24 h. Significant increment of guaiacol peroxidase activity was obtained in all treated groups in comparison with the control after 72 h. Glutathione-S-transferase activity increased after 48 h seedling treatment with NaCl or SNP and 72 h seedling incubation with NaCl. Under experimental conditions used, glutathione reductase activity was virtually not affected. It is proposed that SNP can be used to prevent salt-induced oxidative stress in maize.

  11. Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay.

    PubMed

    Smakowska, Elwira; Skibior-Blaszczyk, Renata; Czarna, Malgorzata; Kolodziejczak, Marta; Kwasniak-Owczarek, Malgorzata; Parys, Katarzyna; Funk, Christiane; Janska, Hanna

    2016-08-01

    FTSH4 is one of the inner membrane-embedded ATP-dependent metalloproteases in mitochondria of Arabidopsis (Arabidopsis thaliana). In mutants impaired to express FTSH4, carbonylated proteins accumulated and leaf morphology was altered when grown under a short-day photoperiod, at 22°C, and a long-day photoperiod, at 30°C. To provide better insight into the function of FTSH4, we compared the mitochondrial proteomes and oxyproteomes of two ftsh4 mutants and wild-type plants grown under conditions inducing the phenotypic alterations. Numerous proteins from various submitochondrial compartments were observed to be carbonylated in the ftsh4 mutants, indicating a widespread oxidative stress. One of the reasons for the accumulation of carbonylated proteins in ftsh4 was the limited ATP-dependent proteolytic capacity of ftsh4 mitochondria, arising from insufficient ATP amount, probably as a result of an impaired oxidative phosphorylation (OXPHOS), especially complex V. In ftsh4, we further observed giant, spherical mitochondria coexisting among normal ones. Both effects, the increased number of abnormal mitochondria and the decreased stability/activity of the OXPHOS complexes, were probably caused by the lower amount of the mitochondrial membrane phospholipid cardiolipin. We postulate that the reduced cardiolipin content in ftsh4 mitochondria leads to perturbations within the OXPHOS complexes, generating more reactive oxygen species and less ATP, and to the deregulation of mitochondrial dynamics, causing in consequence the accumulation of oxidative damage. PMID:27297677

  12. The effect of N-stearoylethanolamine on cholesterol content, fatty acid composition and protein carbonylation level in rats with alimentary obesity-induced insulin resistance.

    PubMed

    Onopchenko, O V; Kosiakova, G V; Meged, E F; Klimashevsky, V M; Hula, N M

    2014-01-01

    The effect of N-stearoylethanolamine (NSE) on liver free fatty acid composition, cholesterol content and carbonylated protein level in rats with obesity-induced insulin resistance (IR) was studied in the work. The experimental insulin resistance was induced by prolonged high fat diet (58% of energy derived from fat) for 6 months combined with one injection of low-dose (15 mg/kg) of streptozotocin. The lipid assay showed a rise in liver free cholesterol content anda significant reduction in cholesterol esters level. Analyzing liver fatty acid composition, a decrease in polyunsaturated of fatty acid (PUFA) level and an increase in monounsaturated fatty acid (MUFA) content was found. Fatty acid imbalance with high content of MUFA was associated with elevated level ofprotein carbonylation. The NSE administration (50 mg/kg of body weight) for 2 weeks decreased free cholesterol content, increased cholesterol esters level and reduced free oleic fatty acid content in the liver of rats with IR. The effect of NSE on lipid imbalance led to a decrease in protein carbonylation level that may result in improvement of transmembrane protein function under obesity-induced insulin resistance state. PMID:25816612

  13. A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation.

    PubMed

    Voziyan, Paul A; Metz, Thomas O; Baynes, John W; Hudson, Billy G

    2002-02-01

    Reactive carbonyl compounds are formed during autoxidation of carbohydrates and peroxidation of lipids. These compounds are intermediates in the formation of advanced glycation end products (AGE) and advanced lipoxidation end products (ALE) in tissue proteins during aging and in chronic disease. We studied the reaction of carbonyl compounds glyoxal (GO) and glycolaldehyde (GLA) with pyridoxamine (PM), a potent post-Amadori inhibitor of AGE formation in vitro and of development of renal and retinal pathology in diabetic animals. PM reacted rapidly with GO and GLA in neutral, aqueous buffer, forming a Schiff base intermediate that cyclized to a hemiaminal adduct by intramolecular reaction with the phenolic hydroxyl group of PM. This bicyclic intermediate dimerized to form a five-ring compound with a central piperazine ring, which was characterized by electrospray ionization-liquid chromatography/mass spectrometry, NMR, and x-ray crystallography. PM also inhibited the modification of lysine residues and loss of enzymatic activity of RNase in the presence of GO and GLA and inhibited formation of the AGE/ALE N(epsilon)-(carboxymethyl)lysine during reaction of GO and GLA with bovine serum albumin. Our data suggest that the AGE/ALE inhibitory activity and the therapeutic effects of PM observed in diabetic animal models depend, at least in part, on its ability to trap reactive carbonyl intermediates in AGE/ALE formation, thereby inhibiting the chemical modification of tissue proteins. PMID:11729198

  14. Close contacts between carbonyl oxygen atoms and aromatic centers in protein structures: pi...pi or lone-pair...pi interactions?

    PubMed

    Jain, Alok; Purohit, Chandra Shekhar; Verma, Sandeep; Sankararamakrishnan, Ramasubbu

    2007-08-01

    Lone-pair...pi and, more recently, pi...pi interactions have been studied in small molecule crystal structures, and they are the focus of attention in some biomolecules. In this study, we have systematically analyzed 500 high-resolution protein structures (resolution < or =1.8 A) and identified 286 examples in which carbonyl oxygen atoms approach the aromatic centers within a distance of 3.5 A. Contacts involving backbone carbonyl oxygens are frequently observed in helices and, to some extent, in strands. Geometrical characterization indicates that these contacts have geometry in between that of an ideal pi...pi and a lone-pair...pi interaction. Quantum mechanical calculations using 6-311++G** basis sets reveal that these contacts give rise to energetically favorable interactions and, along with MD simulations, indicate that such interactions could stabilize secondary structures.

  15. Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical-like species: a potential pathway for oxidative damage of retinal proteins in diabetes.

    PubMed

    Pennathur, Subramaniam; Ido, Yasuo; Heller, Jozsef I; Byun, Jaeman; Danda, Ratna; Pergola, Pablo; Williamson, Joseph R; Heinecke, Jay W

    2005-06-17

    The pattern of oxidized amino acids in aortic proteins of nonhuman primates suggests that a species resembling hydroxyl radical damages proteins when blood glucose levels are high. However, recent studies argue strongly against a generalized increase in diabetic oxidative stress, which might instead be confined to the vascular wall. Here, we describe a pathway for glucose-stimulated protein oxidation and provide evidence of its complicity in diabetic microvascular disease. Low density lipoprotein incubated with pathophysiological concentrations of glucose became selectively enriched in ortho-tyrosine and meta-tyrosine, implicating a hydroxyl radical-like species in protein damage. Model system studies demonstrated that the reaction pathway requires both a reactive carbonyl group and a polyunsaturated fatty acid, involves lipid peroxidation, and is blocked by the carbonyl scavenger aminoguanidine. To explore the physiological relevance of the pathway, we used mass spectrometry and high pressure liquid chromatography to quantify oxidation products in control and hyperglycemic rats. Hyperglycemia raised levels of ortho-tyrosine, meta-tyrosine, and oxygenated lipids in the retina, a tissue rich in polyunsaturated fatty acids. Rats that received aminoguanidine did not show this increase in protein and lipid oxidation. In contrast, rats with diet-induced hyperlipidemia in the absence of hyperglycemia failed to exhibit increased protein and lipid oxidation products in the retina. Our observations suggest that generation of a hydroxyl radical-like species by a carbonyl/polyunsaturated fatty acid pathway might promote localized oxidative stress in tissues vulnerable to diabetic damage. This raises the possibility that antioxidant therapies that specifically inhibit the pathway might delay the vascular complications of diabetes.

  16. Evaluation of the antioxidative capability of commonly used antioxidants in dermocosmetics by in vivo detection of protein carbonylation in human stratum corneum.

    PubMed

    Tsai, Feng-Jen; Wang, Yuan-Dai; Chen, Cheng-Chi; Hsieh, Chen; Cheng, Zhi-Jiao; Wu, Yu-Jen

    2012-07-01

    We present an in vivo test platform to evaluate the antioxidative capability of seven frequently used dermocosmetic antioxidants on the human stratum corneum (SC). It has been reported that the protein carbonylation could be used as a biomarker for oxidative stress. The current study detects the change of the level of exposed protein carbonyl group in the most outer layer of human SC. The concentration of the antioxidant in each subject emulsion formulation was 0.5% (w/w). The data indicated that alpha-tocopherol (α-Vit E) and ascorbic acid (Vit C) have excellent antioxidative capability and α-Vit E-acetate possesses better than the average antioxidative capability. The bioconversion of α-Vit E-acetate to α-Vit E may occur in the human SC during a less than 2 weeks time course test. Lipoic acid possessed moderate antioxidative capability. Ascorbyl 6-palmitate had a low antioxidative capability. Ascorbic acid 2-glucoside represented an insignificant antioxidative capability. Glutathion (GSH) had no effect on reducing oxidative damage to human SC proteins, implying that the GSH recycling system could be absent in human SC. This test platform is an useful tool to evaluate the antioxidative efficiency of antioxidants on human SC proteins. PMID:22537778

  17. Assessing the Effects of Amoxicillin on Antioxidant Enzyme Activities, Lipid Peroxidation and Protein Carbonyl Content in the Clam Ruditapes philippinarum and the Mussel Mytilus galloprovincialis.

    PubMed

    Matozzo, Valerio; Battistara, Margherita; Marisa, Ilaria; Bertin, Valeria; Orsetti, Alessandro

    2016-10-01

    In this study, we evaluated the capability of amoxicillin (AMX)-one of the most widely used antibiotics worldwide-to induce oxidative stress in both gills and digestive gland from two bivalve species, the clam Ruditapes philippinarum and the mussel Mytilus galloprovincialis. Superoxide dismutase (SOD) and catalase (CAT) activities, as well as the lipid peroxidation levels (LPO) and protein carbonyl content (PCC), were measured in bivalves exposed to 100, 200 and 400 µg AMX/L for 1, 3 and 7 days. The results obtained demonstrated that AMX affected slightly biomarker responses of molluscs. PMID:27510994

  18. Transcriptional regulation of the canine carbonyl reductase 1 gene (cbr1) by the specificity protein 1 (Sp1).

    PubMed

    Quiñones-Lombraña, Adolfo; Cheng, Qiuying; Ferguson, Daniel C; Blanco, Javier G

    2016-10-30

    The clinical use of anthracyclines to treat various canine cancers is limited by the development of cardiotoxicity. The intra-cardiac synthesis of anthracycline C-13 alcohol metabolites (e.g. daunorubicinol) contributes to the development of cardiotoxicity. Canine carbonyl reductase 1 (cbr1) catalyzes the reduction of daunorubicin into daunorubicinol. Recent mapping of the cbr1 locus by sequencing DNA samples from dogs from various breeds revealed a cluster of conserved motifs for the transcription factor Sp1 in the putative promoter region of cbr1. We hypothesized that the variable number of Sp1 motifs could impact the transcription of canine cbr1. In this study, we report the functional characterization of the canine cbr1 promoter. Experiments with reporter constructs and chromatin immunoprecipitation show that cbr1 transcription depends on the binding of Sp1 to the proximal promoter. Site-directed mutagenesis experiments suggest that the variable number of Sp1 motifs impacts the transcription of canine cbr1. Inhibition of Sp1-DNA binding decreased canine cbr1 mRNA levels by 54% in comparison to controls, and also decreased enzymatic carbonyl reductase activity for the substrates daunorubicin (16%) and menadione (23%). The transactivation of Sp1 increased the expression of cbr1 mRNA (67%), and increased carbonyl reductase activity for daunorubicin (35%) and menadione (27%). These data suggest that the variable number of Sp1 motifs in the canine cbr1 promoter may impact the pharmacodynamics of anthracyclines in canine cancer patients.

  19. Frequency-Selective Heteronuclear Dephasing and Selective Carbonyl Labeling to Deconvolute Crowded Spectra of Membrane Proteins By Magic Angle Spinning NMR

    PubMed Central

    Traaseth, Nathaniel J.; Veglia, Gianluigi

    2011-01-01

    We present a new method that combines carbonyl-selective labeling with frequency-selective heteronuclear recoupling to resolve the spectral overlap of magic angle spinning (MAS) NMR spectra of membrane proteins in fluid lipid membranes with broad lines and high redundancy in the primary sequence. We implemented this approach in both heteronuclear 15N-13Cα and homonuclear 13C-13C dipolar assisted rotational resonance (DARR) correlation experiments. We demonstrate its efficacy for the membrane protein phospholamban reconstituted in fluid PC/PE/PA lipid bilayers. The main advantage of this method is to discriminate overlapped 13Cα resonances by strategically labeling the preceding residue. This method is highly complementary to 13C′i-1-15Ni-13Cαi and 13Cαi-1-15Ni-1-13C′i experiments to discriminate inter-residue spin systems at a minimal cost to signal-to-noise. PMID:21482162

  20. Glutathione redox state, tocochromanols, fatty acids, antioxidant enzymes and protein carbonylation in sunflower seed embryos associated with after-ripening and ageing

    PubMed Central

    Morscher, F.; Kranner, I.; Arc, E.; Bailly, C.; Roach, T.

    2015-01-01

    Background and Aims Loss of seed viability has been associated with deteriorative processes that are partly caused by oxidative damage. The breaking of dormancy, a seed trait that prevents germination in unfavourable seasons, has also been associated with oxidative processes. It is neither clear how much overlap exists between these mechanisms nor is the specific roles played by oxygen and reactive oxygen species. Methods Antioxidant profiles were studied in fresh (dormant) or after-ripened (non-dormant) sunflower (Helianthus annuus) embryos subjected to controlled deterioration at 40 °C and 75 % relative humidity under ambient (21 %) or high O2 (75 %). Changes in seed vigour and viability, dormancy, protein carbonylation and fatty acid composition were also studied. Key Results After-ripening of embryonic axes was accompanied by a shift in the thiol-based cellular redox environment towards more oxidizing conditions. Controlled deterioration under high O2 led to a faster loss of seed dormancy and significant decreases in glutathione reductase and glutathione peroxidase activities, but viability was lost at the same rate as under ambient O2. Irrespective of O2 concentration, the overall thiol-based cellular redox state increased significantly over 21 d of controlled deterioration to strongly oxidizing conditions and then plateaued, while viability continued to decrease. Viability loss was accompanied by a rapid decrease in glucose-6-phosphate-dehydrogenase, which provides NADPH for reductive processes such as required by glutathione reductase. Protein carbonylation, a marker of protein oxidation, increased strongly in deteriorating seeds. The lipid-soluble tocochromanols, dominated by α-tocopherol, and fatty acid profiles remained stable. Conclusions After-ripening, dormancy-breaking during ageing and viability loss appeared to be associated with oxidative changes of the cytosolic environment and proteins in the embryonic axis rather than the lipid

  1. SEECAL: Program to calculate age-dependent

    SciTech Connect

    Cristy, M.; Eckerman, K.F.

    1993-12-01

    This report describes the computer program SEECAL, which calculates specific effective energies (SEE) to specified target regions for ages newborn, 1 y, 5 y, 10 y, 15 y, a 70-kg adult male, and a 58-kg adult female. The dosimetric methodology is that of the International Commission on Radiological Protection (ICRP) and is generally consistent with the schema of the Medical Internal Radiation Dose committee of the US Society of Nuclear Medicine. Computation of SEEs is necessary in the computation of equivalent dose rate in a target region, for occupational or public exposure to radionuclides taken into the body. Program SEECAL replaces the program SEE that was previously used by the Dosimetry Research Group at Oak Ridge National Laboratory. The program SEE was used in the dosimetric calculations for occupational exposures for ICRP Publication 30 and is limited to adults. SEECAL was used to generate age-dependent SEEs for ICRP Publication 56, Part 1. SEECAL is also incorporated into DCAL, a radiation dose and risk calculational system being developed for the Environmental Protection Agency. Electronic copies of the program and data files and this report are available from the Radiation Shielding Information Center at Oak Ridge National Laboratory.

  2. Age-dependent decay in the landscape

    SciTech Connect

    Winitzki, Sergei

    2008-03-15

    The picture of the 'multiverse' arising in diverse cosmological scenarios involves transitions between metastable vacuum states. It was pointed out by Krauss and Dent that the transition rates decrease at very late times, leading to a dependence of the transition probability between vacua on the age of each vacuum region. I investigate the implications of this non-Markovian, age-dependent decay on the global structure of the spacetime in landscape scenarios. I show that the fractal dimension of the eternally inflating domain is precisely equal to 3, instead of being slightly below 3, which is the case in scenarios with purely Markovian, age-independent decay. I develop a complete description of a non-Markovian landscape in terms of a nonlocal master equation. Using this description I demonstrate by an explicit calculation that, under some technical assumptions about the landscape, the probabilistic predictions of our position in the landscape are essentially unchanged, regardless of the measure used to extract these predictions. I briefly discuss the physical plausibility of realizing non-Markovian vacuum decay in cosmology in view of the possible decoherence of the metastable quantum state.

  3. Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures

    PubMed Central

    Schafer, Marissa J.; Dolgalev, Igor; Alldred, Melissa J.; Heguy, Adriana; Ginsberg, Stephen D.

    2015-01-01

    Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan. However, the mosaic of molecular changes responsible for CR benefits remains unclear, particularly in brain regions susceptible to deterioration during aging. We examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses age-dependent signatures of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger-adult (5 months, 2.5 months of feeding) and older-adult (15 months, 12.5 months of feeding) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa protein 1b (Hspa1b) and heat shock 70 kDa protein 5 (Hspa5), protein disulfide isomerase family A member 4 (Pdia4) and protein disulfide isomerase family A member 6 (Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR in adulthood, although the global CR-specific expression profiles at younger and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within the hippocampal CA1 sector. PMID:26221964

  4. Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures.

    PubMed

    Schafer, Marissa J; Dolgalev, Igor; Alldred, Melissa J; Heguy, Adriana; Ginsberg, Stephen D

    2015-01-01

    Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan. However, the mosaic of molecular changes responsible for CR benefits remains unclear, particularly in brain regions susceptible to deterioration during aging. We examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer's disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses age-dependent signatures of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger-adult (5 months, 2.5 months of feeding) and older-adult (15 months, 12.5 months of feeding) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa protein 1b (Hspa1b) and heat shock 70 kDa protein 5 (Hspa5), protein disulfide isomerase family A member 4 (Pdia4) and protein disulfide isomerase family A member 6 (Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR in adulthood, although the global CR-specific expression profiles at younger and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within the hippocampal CA1 sector. PMID:26221964

  5. Carbonyl reductase inactivation may contribute to mouse lung tumor promotion by electrophilic metabolites of butylated hydroxytoluene: protein alkylation in vivo and in vitro.

    PubMed

    Shearn, Colin T; Fritz, Kristofer S; Meier, Brent W; Kirichenko, Oleg V; Thompson, John A

    2008-08-01

    Promotion of lung tumors in mice by the food additive butylated hydroxytoluene (BHT) is mediated by electrophilic metabolites produced in the target organ. Identifying the proteins alkylated by these quinone methides (QMs) is a necessary step in understanding the underlying mechanisms. Covalent adducts of the antioxidant enzymes peroxiredoxin 6 and Cu,Zn superoxide dismutase were detected previously in lung cytosols from BALB/c mice injected with BHT, and complimentary in vitro studies demonstrated that QM alkylation causes inactivation and enhances oxidative stress. In the present work, adducts of another protective enzyme, carbonyl reductase (CBR), were detected by Western blotting and mass spectrometry in mitochondria from lungs of mice one day after a single injection of BHT and throughout a 28-day period of weekly injections required to achieve tumor promotion. BHT treatment was accompanied by the accumulation of protein carbonyls in lung cytosol from sustained oxidative stress. Studies in vitro demonstrated that CBR activity in lung homogenates was susceptible to concentration- and time-dependent inhibition by QMs. Recombinant CBR underwent irreversible inhibition during QM exposure, and mass spectrometry was utilized to identify alkylation sites at Cys 51, Lys 17, Lys 189, Lys 201, His 28, and His 204. Except for Lys 17, all of these adducts were eliminated as a cause of enzyme inhibition either by chemical modification (cysteine) or site-directed mutagenesis (lysines and histidines). The data demonstrated that Lys 17 is the critical alkylation target, consistent with the role of this basic residue in NADPH binding. These data support the possibility that CBR inhibition occurs in BHT-treated mice, thereby compromising one pathway for inactivating lipid peroxidation products, particularly 4-oxo-2-nonenal. These data, in concert with previous evidence for the inactivation of antioxidant enzymes, provide a molecular basis to explain lung inflammation leading to

  6. Age-dependence of intracranial viscoelastic properties in living rats.

    PubMed

    Shulyakov, Alexander V; Cenkowski, Stefan S; Buist, Richard J; Del Bigio, Marc R

    2011-04-01

    To explore the effect of maturation on intracranial mechanical properties, viscoelastic parameters were determined in 44 live rats at ages 1-2, 10-12, 21, 56-70, and 180 days using instrumented indentation. With the dura mater intact, the apparent modulus of elasticity, the indentation modulus, and viscous behavior were measured in vivo, as well as 1 h after death. In a separate group of 25 rats, brain water, and protein content were determined. A significant increase of the elastic and indentation moduli beginning at 10-12 days after birth and continuing to 180 days was observed. The creep behavior decreased in the postnatal period and stabilized at 21 days. Changes in intracranial biomechanical properties corresponded to a gradual decrease of brain water, and an increase in total protein content, including glial fibrillary acidic protein, myelin basic protein, and neurofilament light chain. Elastic properties were not significantly different comparing the live and dead states. However, there were significant postmortem changes in viscous behavior. Viscoelastic properties of living rat intracranial contents are shown to be age dependent, reflecting the physical and biochemical changes during postnatal development. This may be important for understanding why young and mature brains respond differently in situations of brain trauma and hydrocephalus.

  7. Multiple mechanisms of age-dependent accumulation of amyloid beta protein in rat brain: Prevention by dietary supplementation with N-acetylcysteine, α-lipoic acid and α-tocopherol.

    PubMed

    Sinha, Maitrayee; Bir, Aritri; Banerjee, Anindita; Bhowmick, Pritha; Chakrabarti, Sasanka

    2016-05-01

    The aged brain may be used as a tool to investigate altered metabolism of amyloid beta protein (Aβ42) that may have implications in the pathogenesis of Alzheimer's disease (AD). In the present study, we have observed a striking increase in the amyloid precursor protein (APP) level in the brain cortex of aged rats (22-24 months) along with a mild but statistically significant increase in the level of APP mRNA. Moreover, the activity of β secretase is elevated (nearly 55%) and that of neprilysin diminished (48%) in brain cortex of aged rats compared to that in young rats (4-6 months). All these changes lead to a markedly increased accumulation of Aβ42 in brain cortical tissue of aged rats. Long-term dietary supplementation of rats with a combination of N-acetylcysteine, α-lipoic and α-tocopherol from 18 months onwards daily till the sacrifice of the animals by 22-24 months, attenuates the age-related alterations in amyloid beta metabolism. In separate experiments, a significant impairment of spatial learning and memory has been observed in aged rats, and the phenomenon is remarkably prevented by the dietary supplementation of the aged animals by the same combination of N-acetylcysteine, α-lipoic acid and α-tocopherol. The results call for further explorations of this combination in suitable animal models in ameliorating AD related brain deficits.

  8. To tag or not to tag: a comparative evaluation of immunoaffinity-labeling and tandem mass spectrometry for the identification and localization of posttranslational protein carbonylation by 4-hydroxy-2-nonenal, an end-product of lipid peroxidation.

    PubMed

    Guo, Jia; Prokai, Laszlo

    2011-10-19

    Posttranslational carbonylation of proteins by the covalent attachment of the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) is a biomarker of oxidative stress. Tandem mass spectrometry (MS/MS) has become an essential tool for characterization of this modification. Chemical tagging methods have been used to facilitate the immunoaffinity-based enrichment or even quantification of HNE-modified peptides and proteins. With MS/MS spectra of the untagged modified peptides considered as references, a comparative evaluation is presented focusing on the impact of affinity-tagging with four carbonyl-specific reagents (2,4-dinitrophenyl hydrazine, biotin hydrazide, biotinamidohexanoic acid hydrazide and N'-aminooxymethylcarbonyl-hydrazino D-biotin) on collision-induced dissociation of the tagged HNE-carbonylated peptides. Our study has shown that chemical labeling may not be carried out successfully for all the peptides and with all the reagents. The attachment of a tag usually cannot circumvent the occurrence of strong neutral losses observed with untagged species and, in addition, fragmentation of the introduced tag may also happen. Chemical tagging of certain peptides may, nevertheless, afford more sequence ions upon MS/MS than the untagged carbonylated peptide, especially when Michael addition of the lipid peroxidation product occurs on cysteine residues. Therefore, tagging may increase the confidence of identifications of HNE-modified peptides by database searches.

  9. COATING URANIUM FROM CARBONYLS

    DOEpatents

    Gurinsky, D.H.; Storrs, S.S.

    1959-07-14

    Methods are described for making adherent corrosion resistant coatings on uranium metal. According to the invention, the uranium metal is heated in the presence of an organometallic compound such as the carbonyls of nickel, molybdenum, chromium, niobium, and tungsten at a temperature sufficient to decompose the metal carbonyl and dry plate the resultant free metal on the surface of the uranium metal body. The metal coated body is then further heated at a higher temperature to thermally diffuse the coating metal within the uranium bcdy.

  10. Quantifying Age-dependent Extinction from Species Phylogenies.

    PubMed

    Alexander, Helen K; Lambert, Amaury; Stadler, Tanja

    2016-01-01

    Several ecological factors that could play into species extinction are expected to correlate with species age, i.e., time elapsed since the species arose by speciation. To date, however, statistical tools to incorporate species age into likelihood-based phylogenetic inference have been lacking. We present here a computational framework to quantify age-dependent extinction through maximum likelihood parameter estimation based on phylogenetic trees, assuming species lifetimes are gamma distributed. Testing on simulated trees shows that neglecting age dependence can lead to biased estimates of key macroevolutionary parameters. We then apply this method to two real data sets, namely a complete phylogeny of birds (class Aves) and a clade of self-compatible and -incompatible nightshades (Solanaceae), gaining initial insights into the extent to which age-dependent extinction may help explain macroevolutionary patterns. Our methods have been added to the R package TreePar. PMID:26405218

  11. Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic cells: Protein carbonylation is diminished by ascorbic acid

    PubMed Central

    Chavez, Juan; Chung, Woon-Gye; Miranda, Cristobal L.; Singhal, Mudita; Stevens, Jan F.; Maier, Claudia S.

    2010-01-01

    The protein targets and sites of modification by 4-hydroxy-2(E)-nonenal (HNE) in human monocytic THP-1 cells after exogenous exposure to HNE were examined using a multi-pronged proteomic approach involving electrophoretic, immunoblotting and mass spectrometric methods. Immunoblot analysis using monoclonal anti-HNE antibodies showed several proteins as targets of HNE adduction. Pretreatment of THP-1 cells with ascorbic acid resulted in reduced levels of HNE-protein adducts. Biotinylation of Michael-type HNE adducts using an aldehyde-reactive hydroxylamine-functionalized probe (aldehyde-reactive probe, ARP) and subsequent enrichment facilitated the identification and site-specific assignment of the modifications by LC-MS/MS analysis. Sixteen proteins were unequivocally identified as targets of HNE adduction and eighteen sites of HNE modification at Cys and His residues were assigned. HNE exposure of THP-1 cells resulted in the modification of proteins involved in cytoskeleton organization and regulation, proteins associated with stress responses and enzymes of the glycolytic and other metabolic pathways. This study yielded the first evidence of site-specific adduction of HNE to Cys-295 in tubulin α-1B chain, Cys-351 and Cys-499 in α-actinin-4, Cys-328 in vimentin, Cys-369 in D-3-phosphoglycerate dehydrogenase and His-246 in aldolase A. PMID:20043646

  12. Site-Specific Protein Adducts of 4-Hydroxy-2(E)-Nonenal in Human THP-1 Monocytic Cells: Protein Carbonylation Is Diminished by Ascorbic Acid

    SciTech Connect

    Chavez, Juan; Chung, Woon-Gye; Miranda, Cristobal L.; Singhal, Mudita; Stevens, Jan F.; Maier, Claudia S.

    2010-01-18

    The protein targets and sites of modification by 4-hydroxy-2(E)-nonenal (HNE) in human monocytic THP-1 cells after exogenous exposure to HNE were examined using a multipronged proteomic approach involving electrophoretic, immunoblotting, and mass spectrometric methods. Immunoblot analysis using monoclonal anti-HNE antibodies showed several proteins as targets of HNE adduction. Pretreatment of THP-1 cells with ascorbic acid resulted in reduced levels of HNE-protein adducts. Biotinylation of Michael-type HNE adducts using an aldehyde-reactive hydroxylamine-functionalized probe (aldehyde-reactive probe, ARP) and subsequent enrichment facilitated the identification and site-specific assignment of the modifications by LC-MS/MS analysis. Sixteen proteins were unequivocally identified as targets of HNE adduction, and eighteen sites of HNE modification at Cys and His residues were assigned. HNE exposure of THP-1 cells resulted in the modification of proteins involved in cytoskeleton organization and regulation, proteins associated with stress responses, and enzymes of the glycolytic and other metabolic pathways. Finally, this study yielded the first evidence of site-specific adduction of HNE to Cys-295 in tubulin α-1B chain, Cys-351 and Cys-499 in α-actinin-4, Cys-328 in vimentin, Cys-369 in d-3-phosphoglycerate dehydrogenase, and His-246 in aldolase A.

  13. THE METAL CARBONYLS.

    PubMed

    Blanchard, A A

    1941-10-01

    When the metal carbonyls were first discovered, their properties were startling because they seemed to violate nearly all the previously recognized generalizations of chemistry. Even to-day the existence of the carbonyls is not particularly emphasized in elementary courses of chemistry because it is rather hard to reconcile them with the first presentations of the generalizations of chemistry. Nevertheless, as the student progresses deeper into the knowledge of chemistry it becomes desirable to include the knowledge of the carbonyls both because they become more comprehensible when viewed in the light of Werner's system of coordination and because they themselves contribute to the comprehension of the Werner theory. As long ago as 1931, Reiff in his discussion of cobalt nitrosyl carbonyl recognized the correlation between the effective atomic number and the volatility of carbonyls. A more recent study of charged Werner coordination complexes, that is, of complex ions, has shown a similar role of the effective atomic number. We are standing on fairly firm ground when we point out the correlation between E.A.N. and the volatility of the carbonyl complexes and the existence of complex ions. Be it noted that we have made no postulates as to the arrangement of the electrons in quantum levels. In the inert gases the outer principal quantum group is supposed always to contain eight electrons. In the carbonyls and other Werner complexes there is no compelling reason to suppose that the electrons in the coordinating layer, be this layer of eight, ten, twelve or sixteen electrons, are not all at the same energy level. Although we have confined our discussion almost exclusively to the property of volatility, the carbonyls are very interesting from the standpoint of several other properties, for example, magnetic susceptibility and dielectric constant. Enthusiasts in the interpretation of such properties try to draw conclusions as to the condition of the electrons, sometimes

  14. Acute nickel carbonyl poisoning.

    PubMed

    Kurta, D L; Dean, B S; Krenzelok, E P

    1993-01-01

    Nickel carbonyl [Ni(CO)4], is formed when metallic nickel combines with carbon monoxide. It is used in the refining process of nickel and as a catalyst in petroleum, plastic, and rubber production. Nickel carbonyl is considered to be one of the most toxic chemicals used industrially and the magnitude of its morbidity and mortality has been compared to that of hydrogen cyanide. A 46-year-old man presented to the emergency department 24 hours after accidental occupational exposure to nickel carbonyl. He admitted to dermal contamination and inhaling the vapor from his clothing after his respiratory protection was removed. On presentation the patient was alert and oriented, complained of shortness of breath, chest tightness, and paresthesias. Examination revealed decreased breath sounds bilaterally and arterial blood gas PO2 of 39% with calculated O2 saturation of 75%. After face mask O2 at 60% his PO2 increased to 85%. The patient required 60% O2 with continuous positive airway pressure of 5 for 4 days. Disulfiram (Antabuse) was administered for the first 2 days until sodium diethyldithiocarbamate (dithiocarb) was obtained. Disulfiram was used because it is metabolized to two molecules of dithiocarb and is hypothetically of value. Dithiocarb was obtained and continued over the next several days. The patient's urine nickel level on the day of admission was 172 micrograms/dL (normal < 5 micrograms/dL) and a serum level of 14.6 micrograms/dL (normal .26-.46 micrograms/dL). The patient's condition gradually improved over the next 10 days. Nickel carbonyl exposure produces mild transient initial symptoms which are followed within 24 hours by more severe life-threatening events.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Acute nickel carbonyl poisoning.

    PubMed

    Kurta, D L; Dean, B S; Krenzelok, E P

    1993-01-01

    Nickel carbonyl [Ni(CO)4], is formed when metallic nickel combines with carbon monoxide. It is used in the refining process of nickel and as a catalyst in petroleum, plastic, and rubber production. Nickel carbonyl is considered to be one of the most toxic chemicals used industrially and the magnitude of its morbidity and mortality has been compared to that of hydrogen cyanide. A 46-year-old man presented to the emergency department 24 hours after accidental occupational exposure to nickel carbonyl. He admitted to dermal contamination and inhaling the vapor from his clothing after his respiratory protection was removed. On presentation the patient was alert and oriented, complained of shortness of breath, chest tightness, and paresthesias. Examination revealed decreased breath sounds bilaterally and arterial blood gas PO2 of 39% with calculated O2 saturation of 75%. After face mask O2 at 60% his PO2 increased to 85%. The patient required 60% O2 with continuous positive airway pressure of 5 for 4 days. Disulfiram (Antabuse) was administered for the first 2 days until sodium diethyldithiocarbamate (dithiocarb) was obtained. Disulfiram was used because it is metabolized to two molecules of dithiocarb and is hypothetically of value. Dithiocarb was obtained and continued over the next several days. The patient's urine nickel level on the day of admission was 172 micrograms/dL (normal < 5 micrograms/dL) and a serum level of 14.6 micrograms/dL (normal .26-.46 micrograms/dL). The patient's condition gradually improved over the next 10 days. Nickel carbonyl exposure produces mild transient initial symptoms which are followed within 24 hours by more severe life-threatening events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8383493

  16. Metabolic energy sensors (AMPK and SIRT1), protein carbonylation and cardiac failure as biomarkers of thermal stress in an intertidal limpet: linking energetic allocation with environmental temperature during aerial emersion.

    PubMed

    Han, Guo-dong; Zhang, Shu; Marshall, David J; Ke, Cai-huan; Dong, Yun-wei

    2013-09-01

    The effects of heat stress on organisms are manifested at the levels of organ function, metabolic activity, protein stability and gene expression. Here, we examined effects of high temperature on the intertidal limpet Cellana toreuma to determine how the temperatures at which (1) organ failure (cardiac function), (2) irreversible protein damage (carbonylation) and (3) expression of genes encoding proteins involved in molecular chaperoning (hsp70 and hsp90) and metabolic regulation (ampk and sirt1) occur compare with field temperatures, which commonly exceed 30°C and can reach 46°C. Heart failure, indexed by the Arrhenius break temperature, occurred at 34.3°C. Protein carbonylation rose significantly at 38°C. Genes for heat shock proteins HSP70 (hsp70) and HSP90 (hsp90), for two subunits of AMP-activated protein kinase (AMPK) (ampkα and ampkβ) and for histone/protein deacetylase SIRT1 (sirt1) all showed increased expression at 30°C. Temperatures of maximal expression differed among genes, as did temperatures at which upregulation ceased. Expression patterns for ampk and sirt1 indicate that heat stress influenced cellular energy homeostasis; above ~30°C, upregulation of ATP-generating pathways is suggested by elevated expression of genes for ampk; an altered balance between reliance on carbohydrate and lipid fuels is indicated by changes in expression of sirt1. These results show that C. toreuma commonly experiences temperatures that induce expression of genes associated with the stress response (hsp70 and hsp90) and regulation of energy metabolism (ampk and sirt1). At high temperatures, there is likely to be a shift away from anabolic processes such as growth to catabolic processes, to provide energy for coping with stress-induced damage, notably to proteins. PMID:23685977

  17. Age-dependent protection quantities for external photon irradiation.

    PubMed

    Chou, D P; Wang, J N; Chen, I J

    2001-01-01

    The age-dependent conversion coefficients of the protection quantities, the equivalent dose and the effective dose defined by the International Commission on Radiological Protection (ICRP), are obtained. A Monte Carlo computer code and the age-dependent hermaphrodite mathematical phantoms of six age groups: newborn, 1, 5, 10, 15 years old and adult are used for the evaluation. Twenty-three photon source energies from 10 keV to 10 MeV and six kinds of irradiation geometries: AP, PA, RLAT, LLAT, ROT, and ISO are chosen in the calculation. The evaluated conversion coefficients for the adult are compared with those in ICRP Publication 74 with good agreement. The conversion coefficients of the equivalent dose and the effective dose increase while the age of the phantom decreases, but with some exceptions for the AP irradiation geometry under certain conditions. PMID:11605795

  18. Age-dependent diet choice in an avian top predator.

    PubMed

    Rutz, Christian; Whittingham, Mark J; Newton, Ian

    2006-03-01

    Age-dependent breeding performance is arguably one of the best-documented phenomena in ornithology. The existence of age-related trends has major implications for life-history theory, but the proximate reasons for these patterns remain poorly understood. It has been proposed that poor breeding performance of young individuals might reflect lack of foraging skills. We investigated this possibility in a medium-sized, powerful raptor-the northern goshawk Accipiter gentilis. Male goshawks are responsible for providing their females and their offspring with food. We hypothesized that young males may generally show poor breeding performance or even delay breeding, because they lack the experience to hunt efficiently-especially, their principal avian prey, the feral pigeon Columba livia. Our study exploited a rare 'natural experiment', the expansion phase of an urban population, where intraspecific interference was negligible and many young males bred successfully. This enabled us to examine the improvement of foraging skills in a larger sample of young individuals, and in more controlled conditions than usually possible. Using data from individually identified male breeders, we show that, consistent with our hypothesis, the proportion of pigeons in the diet increased significantly with male age, for at least the first three years of life. Other studies have shown a parallel increase in productivity, and a positive effect of a pigeon-rich diet on brood size and nestling condition, stressing the potential fitness relevance of this prey species for goshawks. Our results suggest a causal link between patterns of age-dependence in foraging ecology and reproductive performance. Furthermore, our study is, to our knowledge, the first demonstration that prey choice of breeders, which might reflect individual hunting skills, is age-dependent in a raptor. PMID:16537129

  19. Anomalous scaling in an age-dependent branching model.

    PubMed

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

  20. Anomalous scaling in an age-dependent branching model.

    PubMed

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point. PMID:25768548

  1. Age-dependent social learning in a lizard.

    PubMed

    Noble, Daniel W A; Byrne, Richard W; Whiting, Martin J

    2014-07-01

    Evidence of social learning, whereby the actions of an animal facilitate the acquisition of new information by another, is taxonomically biased towards mammals, especially primates, and birds. However, social learning need not be limited to group-living animals because species with less interaction can still benefit from learning about potential predators, food sources, rivals and mates. We trained male skinks (Eulamprus quoyii), a mostly solitary lizard from eastern Australia, in a two-step foraging task. Lizards belonging to 'young' and 'old' age classes were presented with a novel instrumental task (displacing a lid) and an association task (reward under blue lid). We did not find evidence for age-dependent learning of the instrumental task; however, young males in the presence of a demonstrator learnt the association task faster than young males without a demonstrator, whereas old males in both treatments had similar success rates. We present the first evidence of age-dependent social learning in a lizard and suggest that the use of social information for learning may be more widespread than previously believed.

  2. Age dependency of neointima formation on vascular prostheses in dogs.

    PubMed

    Noishiki, Y; Yamane, Y; Ichikawa, Y; Yamazaki, I; Yamamoto, K; Kosuge, T; Manabe, T; Mo, M

    2000-09-01

    Neointima formed quickly on vascular prostheses implanted in young dogs but not in aged dogs. Previously, we found that impeding neointima formation on vascular prostheses occurred more frequently in aged animals. From these observations, we hypothesized that neointima formation was age-dependent in dogs. To test the hypothesis, 26 fabric Dacron vascular prostheses were analyzed. Half of them were retrieved from aged dogs (more than 13 years old) while the other half were from young ones (less than 1 year old). The grafts were harvested at 8 weeks and 3 months after implantation. The graft surfaces were photographed and analyzed by computer for the ratio of the areas with and without thrombus. Light and scanning electron microscopic observation revealed that most of the thrombus-free areas were lined with endothelial cells. Then the endothelialized areas were calculated. Using data obtained from macroscopic, light microscopic, and scanning electron microscopic observations, the arithmetic means were calculated as the degree of neointima formation. In young animals, the degrees at 8 weeks and at 3 months were 89.1 +/- 8.5% (mean +/- SD) and 95.7 +/- 3.3%, respectively. In old animals, they were 27.9 +/- 5.9% and 31.5 +/- 6. 8%, respectively. From these results, we concluded that neointima formation was age-dependent in dogs.

  3. Role of Mitochondrial Complex IV in Age-Dependent Obesity.

    PubMed

    Soro-Arnaiz, Ines; Li, Qilong Oscar Yang; Torres-Capelli, Mar; Meléndez-Rodríguez, Florinda; Veiga, Sónia; Veys, Koen; Sebastian, David; Elorza, Ainara; Tello, Daniel; Hernansanz-Agustín, Pablo; Cogliati, Sara; Moreno-Navarrete, Jose Maria; Balsa, Eduardo; Fuertes, Esther; Romanos, Eduardo; Martínez-Ruiz, Antonio; Enriquez, Jose Antonio; Fernandez-Real, Jose Manuel; Zorzano, Antonio; De Bock, Katrien; Aragonés, Julián

    2016-09-13

    Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion. PMID:27626667

  4. Age-dependent protection quantities for external neutron irradiation.

    PubMed

    Chou, D P; Wang, J N; Chen, I J; Chang, B J

    2003-01-01

    Based on the recommendations issued by the International Commission on Radiological Protection (ICRP), equivalent doses and effective doses for different ages are obtained for external neutron sources. The calculations at 28 neutron energies from 1 x 10(-9) MeV to 20 MeV are carried out for six irradiation geometries: AP, PA, RLAT, LLAT, ROT and ISO. An age-dependent anthropomorphic mathematical phantom series of six age groups: newborn, 1, 5, 10, 15 years old and adult is used with the Monte Carlo computer code MCNP for the dose evaluations. The results for adults are compared with those in ICRP Publication 74 and are in good agreement. At low energies the effective doses increase as the phantom age increases, but at high energics they decrease with increasing age for the AP, PA, ROT and ISO irradiation geometries. In the whole energy region the effective doses decrease as the phantom age increases for the RLAT and LLAT irradiation geometries. The age-dependent equivalent doses behave similarly to the effective doses, with some exceptions caused by the influence of the organ position. PMID:12862238

  5. High throughput assay for evaluation of reactive carbonyl scavenging capacity☆

    PubMed Central

    Vidal, N.; Cavaille, J.P.; Graziani, F.; Robin, M.; Ouari, O.; Pietri, S.; Stocker, P.

    2014-01-01

    Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal. PMID:24688895

  6. High throughput assay for evaluation of reactive carbonyl scavenging capacity.

    PubMed

    Vidal, N; Cavaille, J P; Graziani, F; Robin, M; Ouari, O; Pietri, S; Stocker, P

    2014-01-01

    Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.

  7. Targeting Reactive Carbonyl Species with Natural Sequestering Agents.

    PubMed

    Hwang, Sung Won; Lee, Yoon-Mi; Aldini, Giancarlo; Yeum, Kyung-Jin

    2016-01-01

    Reactive carbonyl species generated by the oxidation of polyunsaturated fatty acids and sugars are highly reactive due to their electrophilic nature, and are able to easily react with the nucleophilic sites of proteins as well as DNA causing cellular dysfunction. Levels of reactive carbonyl species and their reaction products have been reported to be elevated in various chronic diseases, including metabolic disorders and neurodegenerative diseases. In an effort to identify sequestering agents for reactive carbonyl species, various analytical techniques such as spectrophotometry, high performance liquid chromatography, western blot, and mass spectrometry have been utilized. In particular, recent advances using a novel high resolution mass spectrometry approach allows screening of complex mixtures such as natural products for their sequestering ability of reactive carbonyl species. To overcome the limited bioavailability and bioefficacy of natural products, new techniques using nanoparticles and nanocarriers may offer a new attractive strategy for increased in vivo utilization and targeted delivery of bioactives. PMID:26927058

  8. Peripheral Surgical Wounding and Age-Dependent Neuroinflammation in Mice

    PubMed Central

    Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong

    2014-01-01

    Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ) have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Iba1 positive cells (the marker of microglia activation), CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients. PMID:24796537

  9. Age-dependent forest carbon sink: Estimation via inverse modeling

    NASA Astrophysics Data System (ADS)

    Zhou, Tao; Shi, Peijun; Jia, Gensuo; Dai, Yongjiu; Zhao, Xiang; Shangguan, Wei; Du, Ling; Wu, Hao; Luo, Yiqi

    2015-12-01

    Forests have been recognized to sequester a substantial amount of carbon (C) from the atmosphere. However, considerable uncertainty remains regarding the magnitude and time course of the C sink. Revealing the intrinsic relationship between forest age and C sink is crucial for reducing uncertainties in prediction of forest C sink potential. In this study, we developed a stepwise data assimilation approach to combine a process-based Terrestrial ECOsystem Regional model, observations from multiple sources, and stochastic sampling to inversely estimate carbon cycle parameters including carbon sink at different forest ages for evergreen needle-leaved forests in China. The new approach is effective to estimate age-dependent parameter of maximal light-use efficiency (R2 = 0.99) and, accordingly, can quantify a relationship between forest age and the vegetation and soil C sinks. The estimated ecosystem C sink increases rapidly with age, peaks at 0.451 kg C m-2 yr-1 at age 22 years (ranging from 0.421 to 0.465 kg C m-2 yr-1), and gradually decreases thereafter. The dynamic patterns of C sinks in vegetation and soil are significantly different. C sink in vegetation first increases rapidly with age and then decreases. C sink in soil, however, increases continuously with age; it acts as a C source when the age is less than 20 years, after which it acts as a sink. For the evergreen needle-leaved forest, the highest C sink efficiency (i.e., C sink per unit net primary productivity) is approximately 60%, with age between 11 and 43 years. Overall, the inverse estimation of carbon cycle parameters can make reasonable estimates of age-dependent C sequestration in forests.

  10. A Method to Site-Specifically Identify and Quantitate Carbonyl End Products of Protein Oxidation Using Oxidation-Dependent Element Coded Affinity Tags (O-ECAT) and NanoLiquid Chromatography Fourier Transform Mass Spectrometry

    SciTech Connect

    Lee, S; Young, N L; Whetstone, P A; Cheal, S M; Benner, W H; Lebrilla, C B; Meares, C F

    2005-08-25

    Protein oxidation is linked to cellular stress, aging, and disease. Protein oxidations that result in reactive species are of particular interest, since these reactive oxidation products may react with other proteins or biomolecules in an unmediated and irreversible fashion, providing a potential marker for a variety of disease mechanisms. We have developed a novel system to identify and quantitate, relative to other states, the sites of oxidation on a given protein. A specially designed Oxidation-dependent carbonyl-specific Element-Coded Affinity Mass Tag (O-ECAT), AOD, ((S)-2-(4-(2-aminooxy)-acetamido)-benzyl)-1, 4, 7, 10-tetraazacyclododecane-N, N', N'', N'''-tetraacetic acid, is used to covalently tag the residues of a protein oxidized to aldehyde or keto end products. After proteolysis, the resulting AOD-tagged peptides are affinity purified, and analyzed by nanoLC-FTICR-MS, which provides high specificity in extracting co-eluting AOD mass pairs with a unique mass difference and affords relative quantitation based on isotopic ratios. Using this methodology, we have mapped the surface oxidation sites on a model protein, recombinant human serum albumin (rHSA) in its native form (as purchased) and after FeEDTA oxidation. A variety of modified amino acid residues including lysine, arginine, proline, histidine, threonine, aspartic and glutamic acids, were found to be oxidized to aldehyde and keto end products. The sensitivity of this methodology is shown by the number of peptides identified, twenty peptides on the native protein and twenty-nine after surface oxidation using FeEDTA and ascorbate. All identified peptides map to the surface of the HSA crystal structure validating this method for identifying oxidized amino acids on protein surfaces. In relative quantitation experiments between FeEDTA oxidation and native protein oxidation, identified sites showed different relative propensities towards oxidation independent of amino acid residue. We expect to extend

  11. 49 CFR 173.198 - Nickel carbonyl.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Nickel carbonyl. 173.198 Section 173.198... Nickel carbonyl. (a) Nickel carbonyl must be packed in specification steel or nickel cylinders as prescribed for any compressed gas except acetylene. A cylinder used exclusively for nickel carbonyl may...

  12. 49 CFR 173.198 - Nickel carbonyl.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Nickel carbonyl. 173.198 Section 173.198... Nickel carbonyl. (a) Nickel carbonyl must be packed in specification steel or nickel cylinders as prescribed for any compressed gas except acetylene. A cylinder used exclusively for nickel carbonyl may...

  13. 49 CFR 173.198 - Nickel carbonyl.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nickel carbonyl. 173.198 Section 173.198... Nickel carbonyl. (a) Nickel carbonyl must be packed in specification steel or nickel cylinders as prescribed for any compressed gas except acetylene. A cylinder used exclusively for nickel carbonyl may...

  14. 49 CFR 173.198 - Nickel carbonyl.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Nickel carbonyl. 173.198 Section 173.198... Nickel carbonyl. (a) Nickel carbonyl must be packed in specification steel or nickel cylinders as prescribed for any compressed gas except acetylene. A cylinder used exclusively for nickel carbonyl may...

  15. 49 CFR 173.198 - Nickel carbonyl.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nickel carbonyl. 173.198 Section 173.198... Nickel carbonyl. (a) Nickel carbonyl must be packed in specification steel or nickel cylinders as prescribed for any compressed gas except acetylene. A cylinder used exclusively for nickel carbonyl may...

  16. Biological factors and age-dependence of primary motor cortex experimental plasticity.

    PubMed

    Polimanti, Renato; Simonelli, Ilaria; Zappasodi, Filippo; Ventriglia, Mariacarla; Pellicciari, Maria Concetta; Benussi, Luisa; Squitti, Rosanna; Rossini, Paolo Maria; Tecchio, Franca

    2016-02-01

    To evaluate whether the age-dependence of brain plasticity correlates with the levels of proteins involved in hormone and brain functions we executed a paired associative stimulation (PAS) protocol and blood tests. We measured the PAS-induced plasticity in the primary motor cortex. Blood levels of the brain-derived neurotrophic factor (BDNF), estradiol, the insulin-like growth factor (IGF)-1, the insulin-like growth factor binding protein (IGFBP)-3, progesterone, sex hormone-binding globulin (SHBG), testosterone, and the transforming growth factor beta 1 (TGF-β1) were determined in 15 healthy men and 20 healthy women. We observed an age-related reduction of PAS-induced plasticity in females that it is not present in males. In females, PAS-induced plasticity displayed a correlation with testosterone (p = 0.006) that became a trend after the adjustment for the age effect (p = 0.078). In males, IGF-1 showed a nominally significant correlation with the PAS-induced plasticity (p = 0.043). In conclusion, we observed that hormone blood levels (testosterone in females and IGF-1 in males) may be involved in the age-dependence of brain plasticity.

  17. A comprehensive approach to age-dependent dosimetric modeling

    SciTech Connect

    Leggett, R.W.; Cristy, M.; Eckerman, K.F.

    1986-01-01

    In the absence of age-specific biokinetic models, current retention models of the International Commission on Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper we discuss a comprehensive approach to age-dependent dosimetric modeling in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates or risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks.

  18. Age-dependent fatigue behaviour of human cortical bone.

    PubMed

    Diab, T; Sit, S; Kim, D; Rho, J; Vashishth, D

    2005-01-01

    Despite a general understanding that bone quality contributes to skeletal fragility, very little information exits on the age-dependent fatigue behavior of human bone. In this study four-point bending fatigue tests were conducted on aging bone in conjunction with the analysis of stiffness loss and preliminary investigation of nanoindentation based measurements of local tissue stiffness and histological evaluation of resultant tensile and compressive damage to identify the damage mechanism responsible for the increase in age-related bone fragility. The results obtained show that there is an exponential decrease in fatigue life with age, and old bone exhibits different modulus degradation profiles than young bone. In addition, this study provides preliminary evidence indicating that during fatigue loading, younger bone formed diffuse damage, lost local tissue stiffness on the tensile side. Older bone, in contrast, formed linear microcracks lost local tissue stiffness on the compressive side. Thus, the propensity of aging human bone to form more linear microcracks than diffuse damage may be a significant contributor to bone quality, and age related fragility in bone.

  19. Demographic drivers of age-dependent sexual selection.

    PubMed

    Martin, A M; Festa-Bianchet, M; Coltman, D W; Pelletier, F

    2016-07-01

    Sexual selection has a critical role in evolution, and it is fundamental to identify what ecological factors drive its variation. Disentangling the ecological correlates of sexual selection over the long term, however, is challenging and has rarely been done in nature. We sought to assess how demographic changes influenced the intensity, direction and form of sexual selection and whether selective pressures varied with age. We tested whether breeder sex ratio, number of competitors and age structure influenced selection differentials on horn length of wild bighorn rams (Ovis canadensis) of different age classes on Ram Mountain, Alberta. We used 21 years of data including a detailed pedigree, demographic parameters and repeated morphological measurements. Sexual selection on horn length of males of all ages was directional and positive. Selection intensity increased with the number of competitors, reflecting male-male encounter rate during the rut, but was independent of breeder sex ratio or age structure. This result can also be linked to changes in population size because the number of competitors was highly correlated to total number of sheep. This demographic effect likely arises from age-dependent mating tactics. Males aged 2-4 years are weakly competitive and experienced stronger sexual selection as they accounted for a greater proportion of all males. Selection experienced by mature males appeared independent of demography. Our study provides a rare description of the demographic determinants of sexual selection in nature.

  20. Demographic drivers of age-dependent sexual selection.

    PubMed

    Martin, A M; Festa-Bianchet, M; Coltman, D W; Pelletier, F

    2016-07-01

    Sexual selection has a critical role in evolution, and it is fundamental to identify what ecological factors drive its variation. Disentangling the ecological correlates of sexual selection over the long term, however, is challenging and has rarely been done in nature. We sought to assess how demographic changes influenced the intensity, direction and form of sexual selection and whether selective pressures varied with age. We tested whether breeder sex ratio, number of competitors and age structure influenced selection differentials on horn length of wild bighorn rams (Ovis canadensis) of different age classes on Ram Mountain, Alberta. We used 21 years of data including a detailed pedigree, demographic parameters and repeated morphological measurements. Sexual selection on horn length of males of all ages was directional and positive. Selection intensity increased with the number of competitors, reflecting male-male encounter rate during the rut, but was independent of breeder sex ratio or age structure. This result can also be linked to changes in population size because the number of competitors was highly correlated to total number of sheep. This demographic effect likely arises from age-dependent mating tactics. Males aged 2-4 years are weakly competitive and experienced stronger sexual selection as they accounted for a greater proportion of all males. Selection experienced by mature males appeared independent of demography. Our study provides a rare description of the demographic determinants of sexual selection in nature. PMID:27090379

  1. Age-dependent lens changes in galactose-fed dogs.

    PubMed

    Lackner, P A; Rodriguez, L; Sato, S; Lizak, M J; Wyman, M; Kador, P F

    1997-03-01

    Aldose reductase initiated sugar cataract formation in 9-month old galactose-fed dogs has been documented to progress from an accentuation of lens sutures (1 month after initial feeding) to the appearance of cortical vacuoles (3 months), cortical opacities (4-6 months) and eventually the progressive formation of a clear zone at the cortical equatorial regions of the cataractous lenses (> 12 months). Here, the effect of age on the onset and degree of sugar cataract formation has been investigated in beagles fed a 30% galactose diet starting at 2, 6, and 24 months of age. Cataract formation was monitored by slit lamp and retroillumination microscopy. Compared to 9-month old dogs, cataract formation in the younger dogs was more rapid and the lens changes were more severe. In the 2-month old group of dogs, galactose-feeding resulted in a rapid formation of dense cataracts which began to resorb after 106 days of galactose feeding with only opaque nuclear remnants remaining after eight months. These changes were mirrored by age-dependent reductions of lenticular NADPH-dependent reductase activity.

  2. Age-dependent changes in matrix composition and organization at the ligament-to-bone insertion.

    PubMed

    Wang, I-Ning E; Mitroo, Siddarth; Chen, Faye H; Lu, Helen H; Doty, Stephen B

    2006-08-01

    Injuries to the anterior cruciate ligament (ACL) often occur at the ligament-to-bone insertion site; thus, an in-depth understanding of the native insertion is critical in identifying the etiology of failure and devising optimal treatment protocols for ACL injuries. The objective of this study is to conduct a systematic characterization of the ACL-to-bone interface, focusing on structural and compositional changes as a function of age. Using a bovine model, three age groups were studied: Neonatal (1-7 days old), Immature (2-6 months old), and Mature (2-5 years old). The distribution of types I, II, X collagen, decorin, cartilage oligomeric matrix protein (COMP), glycosaminoglycan (GAG), alkaline phosphatase (ALP) activity, and minerals at the ACL-to-bone insertion were examined. Additionally, cell aspect ratio, size, and distribution across the insertion were quantified. The ACL-to-bone insertion is divided into four regions: ligament, nonmineralized interface, mineralized interface, and bone. Both region-dependent and age-dependent structural and compositional changes at the insertion site were observed in this study. The interface in the skeletally immature group resembled articular cartilage, while the adult interface was similar to fibrocartilaginous tissue. Age-dependent changes in extracellular matrix composition (type X collagen, sulfated glycosaminoglycan), cellularity, ALP activity, and mineral distribution were also found. Marked differences in collagen fiber orientation between the femoral and tibial insertions were observed, and these differences became more pronounced with age.

  3. Age-dependent ascending aorta mechanics assessed through multiphase CT.

    PubMed

    Martin, Caitlin; Sun, Wei; Primiano, Charles; McKay, Raymond; Elefteriades, John

    2013-12-01

    Quantification of the age- and gender-specific in vivo mechanical characteristics of the ascending aorta (AA) will allow for identification of abnormalities aside from changes brought on by aging alone. Multiphase clinical CT scans of 45 male patients between the ages of 30 and 79 years were analyzed to assess age-dependent in vivo AA characteristics. The three-dimensional AA geometry for each patient was reconstructed from the CT scans for 9-10 phases throughout the cardiac cycle. The AA circumference was measured during each phase and was used to determine the corresponding diameter, circumferential strain, and wall tension at each phase. The pressure-strain modulus was also determined for each patient. The mean diastolic AA diameter was significantly smaller among young (42.6 ± 5.2 years) at 29.9 ± 2.8 mm than old patients (69.0 ± 5.2 years) at 33.2 ± 3.2 mm. The circumferential AA strain from end-diastole to peak-systole decreased from 0.092 ± 0.03 in young to 0.056 ± 0.03 in old patients. The pressure-strain modulus increased two-fold from 68.4 ± 30.5 kPa in young to 162.0 ± 93.5 kPa in old patients, and the systolic AA wall tension increased from 268.5 ± 31.3 kPa in young to 304.9 ± 49.2 kPa in old patients. The AA dilates and stiffens with aging which increases the vessel wall tension, likely predisposing aneurysm and dissection.

  4. Age dependency of cerebral oxygenation assessed with near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Colier, Willy N.; van Haaren, Nicole J.; van de Ven, Marjo J.; Folgering, Hans T.; Oeseburg, Berend

    1997-04-01

    Near-IR spectroscopy (NIRS) is an optical technique that provides information on cerebral tissue oxygenation and hemodynamics on a continuous, direct, and noninvasive basis. It is used to determine cerebral blood volume (CBV) and cerebrovascular CO2 reactivity during normoxic hyper- and hypocapnia in a group of 28 healthy volunteers aged 20 to 83 years. The main focus is on to the age dependency of the measured variables. The influence of changes in minute ventilation during normocapnia on the cerebral oxygenation was also studied. The mean CBV in age was, for 20 to 30 years, 2.14 +/- 0.51 ml/100 g of brain tissue; for 45 to 50 years, 1.92 +/- 0.40 ml/100 g; and for 70 to 83 years, 1.47 +/- 0.55 ml/100 g. The CBV showed a significant decease with advancing age. No influence was found for a change in minute ventilation on cerebral oxygenation. During hypercapnia cerebral blood flow (CBF) significantly increased in al age groups, with a factor of 1.31 +/- 0.17 kPa-1, 1.64 +/- 1.39 kPa-1, and 2.4 +/- 1.7 kPa-1, respectively, for the three age groups. The difference in change among the age groups was not statistically significant. The trend seen was an increased change in CBF with advancing age. During hypocapnia, the CBF significantly decreased in all age groups, with a factor of 0.89 +/- 0.08 kPa-1, 0.89 +/- 0.04 kPa-1, and 0.85 +/- 0.11 kPa-1, respectively. There was no significant difference among the age groups.

  5. Age-Dependent Male Mating Investment in Drosophila pseudoobscura

    PubMed Central

    Dhole, Sumit; Pfennig, Karin S.

    2014-01-01

    Male mating investment can strongly influence fitness gained from a mating. Yet, male mating investment often changes with age. Life history theory predicts that mating investment should increase with age, and males should become less discriminatory about their mate as they age. Understanding age-dependent changes in male behavior and their effects on fitness is important for understanding how selection acts in age-structured populations. Although the independent effects of male or female age have been studied in many species, how these interact to influence male mating investment and fitness is less well understood. We mated Drosophila pseudoobscura males of five different age classes (4-, 8-, 11-, 15-, 19-day old) to either young (4-day) or old (11-day) females, and measured copulation duration and early post-mating fecundity. Along with their independent effects, we found a strong interaction between the effects of male and female ages on male mating investment and fitness from individual matings. Male mating investment increased with male age, but this increase was more prominent in matings with young females. Male D. pseudoobscura made smaller investments when mating with old females. The level of such discrimination based on female age, however, also changed with male age. Intermediate aged males were most discriminatory, while the youngest and the oldest males did not discriminate between females of different ages. We also found that larger male mating investments resulted in higher fitness payoffs. Our results show that male and female ages interact to form a complex pattern of age-specific male mating investment and fitness. PMID:24586373

  6. An age-dependent feedback control model of calcium dynamics in yeast cells.

    PubMed

    Tang, Fusheng; Liu, Weijiu

    2010-06-01

    The functional decline of selected proteins or organelles leads to aging at the intracellular level. Identification of these proteins or organelles is usually challenging to traditional single-factor approaches since these factors are inter-connected via feedback or feedforward controls. Establishing a feedback control model to simulate the interactions of multiple factors is an insightful approach to guide the search for proteins involved in aging. However, there are only a few mathematical models describing the age-dependent accumulation of DNA mutations, which are directly or indirectly induced by deterioration of the intracellular environment including alteration of calcium homeostasis, a contributor of aging. Thus, based on Cui and Kaandorp's model, we develop an age-dependent mathematical model for the calcium homeostasis in budding yeast Saccharomyces cerevisiae. Our model contains cell cycle-dependent aging factors and can qualitatively reproduce calcium shocks and calcium accumulations in cells observed in experiments. Using this model, we predict calcium oscillations in wild type, pmc1 Delta, and pmr1 Delta cells. This prediction suggests that Pmr1p plays a major role in regulating cytosolic calcium. Combining the model with our experimental lifespan data, we predict an upper-limit of cytosolic calcium tolerance for cell survival. This prediction indicates that, for aged cells (>35 generations), no pmr1 Delta can tolerate the cytosolic calcium concentration of 0.1 microM while a very small fraction (1%) of aged wild type cells (>50 generations) can tolerate a high cytosolic calcium concentration of 0.5 microM.

  7. Age Dependent Absolute Plate and Plume Motion Modeling

    NASA Astrophysics Data System (ADS)

    Heaton, D. E.; Koppers, A. A. P.

    2015-12-01

    construct rapidly and represent a time period close to the inception age of the seamount, thus by proxy also the hotspot location. Here we present a new age dependent plate motion model that tests the 'fixed' and 'moving' hotspot hypotheses.

  8. Age-dependent morphological and compositional variations on Ceres

    NASA Astrophysics Data System (ADS)

    Jaumann, Ralf

    2016-04-01

    Extended smooth plains cover the interior of a number of craters on Ceres. Smooth plains appear on different topographic levels associated with pits and flow-like features that overrun crater rims. The material forming these plains also ponds in depressions and smaller craters and cover the pre-existing surface creating distinct geological boundaries. Ikapati crater shows smooth plains on different topographic levels associated with pits and flow-like features that overrun crater rims. The material forming these plains, ponds in depressions and smaller craters and cover the pre-existing surface creating a distinct geological boundary. The interior of Occator also exhibits extended plains of ponded material, multiple flows originating from the center overwhelming the mass wasting deposits from the rim, dome-like features, vents cracks and fissures. Furthermore, crater densities on Occator's floor are lower than those on the ejecta blanket indicating a post-impact formation age of the flows. The flows to the northeast appear to originate from the central region and move slightly uphill. This indicates either a feeding zone that pushes the flows forward by supplying low-viscosity material or a depression of the crater center, possibly after discharging a subsurface reservoir. The plains and flows as well as some areas surrounding the craters appear spectrally blue. Both plains and flow material are characterized in camera and spectrometer visible spectra by a slightly negative slope with a gradual drop off up to 10% in reflectance from 0.5μm to 1μm. Although the spectral variations in the visible are subtle, they are clearly expressed in the color ratio composite. The crater densities of 20 locations across the surface of Ceres with different spectral behavior were analyzed in order to investigate the age dependence of spectral surface features. The results indicate that bluish material is mainly associated with the youngest impact craters on Ceres (< 0.5 Ga) while

  9. Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome.

    PubMed

    Tang, Bin; Wang, Tingting; Wan, Huida; Han, Li; Qin, Xiaoyan; Zhang, Yaoyang; Wang, Jian; Yu, Chunlei; Berton, Fulvia; Francesconi, Walter; Yates, John R; Vanderklish, Peter W; Liao, Lujian

    2015-08-25

    Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by severe intellectual disability and other symptoms including autism. Although caused by the silencing of a single gene, Fmr1 (fragile X mental retardation 1), the complexity of FXS pathogenesis is amplified because the encoded protein, FMRP, regulates the activity-dependent translation of numerous mRNAs. Although the mRNAs that associate with FMRP have been extensively studied, little is known regarding the proteins whose expression levels are altered, directly or indirectly, by loss of FMRP during brain development. Here we systematically measured protein expression in neocortical synaptic fractions from Fmr1 knockout (KO) and wild-type (WT) mice at both adolescent and adult stages. Although hundreds of proteins are up-regulated in the absence of FMRP in young mice, this up-regulation is largely diminished in adulthood. Up-regulated proteins included previously unidentified as well as known targets involved in synapse formation and function and brain development and others linked to intellectual disability and autism. Comparison with putative FMRP target mRNAs and autism susceptibility genes revealed substantial overlap, consistent with the idea that the autism endophenotype of FXS is due to a "multiple hit" effect of FMRP loss, particularly within the PSD95 interactome. Through studies of de novo protein synthesis in primary cortical neurons from KO and WT mice, we found that neurons lacking FMRP produce nascent proteins at higher rates, many of which are synaptic proteins and encoded by FMRP target mRNAs. Our results provide a greatly expanded view of protein changes in FXS and identify age-dependent effects of FMRP in shaping the neuronal proteome.

  10. Fmr1 deficiency promotes age-dependent alterations in the cortical synaptic proteome

    PubMed Central

    Tang, Bin; Wang, Tingting; Wan, Huida; Han, Li; Qin, Xiaoyan; Zhang, Yaoyang; Wang, Jian; Yu, Chunlei; Berton, Fulvia; Francesconi, Walter; Yates, John R.; Vanderklish, Peter W.; Liao, Lujian

    2015-01-01

    Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by severe intellectual disability and other symptoms including autism. Although caused by the silencing of a single gene, Fmr1 (fragile X mental retardation 1), the complexity of FXS pathogenesis is amplified because the encoded protein, FMRP, regulates the activity-dependent translation of numerous mRNAs. Although the mRNAs that associate with FMRP have been extensively studied, little is known regarding the proteins whose expression levels are altered, directly or indirectly, by loss of FMRP during brain development. Here we systematically measured protein expression in neocortical synaptic fractions from Fmr1 knockout (KO) and wild-type (WT) mice at both adolescent and adult stages. Although hundreds of proteins are up-regulated in the absence of FMRP in young mice, this up-regulation is largely diminished in adulthood. Up-regulated proteins included previously unidentified as well as known targets involved in synapse formation and function and brain development and others linked to intellectual disability and autism. Comparison with putative FMRP target mRNAs and autism susceptibility genes revealed substantial overlap, consistent with the idea that the autism endophenotype of FXS is due to a “multiple hit” effect of FMRP loss, particularly within the PSD95 interactome. Through studies of de novo protein synthesis in primary cortical neurons from KO and WT mice, we found that neurons lacking FMRP produce nascent proteins at higher rates, many of which are synaptic proteins and encoded by FMRP target mRNAs. Our results provide a greatly expanded view of protein changes in FXS and identify age-dependent effects of FMRP in shaping the neuronal proteome. PMID:26307763

  11. Age-Dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical Outcomes Following Traumatic Brain Injury

    PubMed Central

    Glushakov, Alexander V.; Arias, Rodrigo A.; Tolosano, Emanuela; Doré, Sylvain

    2016-01-01

    Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most abundant in blood plasma, is involved in the intrinsic molecular defensive mechanism, though its role in TBI is poorly understood. The aim of this study was to investigate the effects of Hp deletion on the anatomical and behavioral outcomes in the controlled cortical impact model using wildtype (WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp−∕−) in two age cohorts [2–4 mo-old (young adult) and 7–8 mo-old (older adult)]. The data obtained suggest age-dependent significant effects on behavioral and anatomical TBI outcomes and recovery from injury. Moreover, in the adult cohort, neurological deficits in Hp−∕− mice at 24 h were significantly improved compared to WT, whereas there were no significant differences in brain pathology between these genotypes. In contrast, in the older adult cohort, Hp−∕− mice had significantly larger lesion volumes compared to WT, but neurological deficits were not significantly different. Immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) revealed significant differences in microglial and astrocytic reactivity between Hp−∕− and WT in selected brain regions of the adult but not the older adult-aged cohort. In conclusion, the data obtained in the study provide clarification on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp that might be involved in complex pathways differentially affecting acute brain trauma outcomes. PMID:27486583

  12. Restraints on backbone conformations in solid state NMR studies of uniformly labeled proteins from quantitative amide 15N–15N and carbonyl 13C–13C dipolar recoupling data

    PubMed Central

    Hu, Kan-Nian; Qiang, Wei; Bermejo, Guillermo A.; Schwieters, Charles D.; Tycko, Robert

    2013-01-01

    Recent structural studies of uniformly 15N, 13C-labeled proteins by solid state nuclear magnetic resonance (NMR) rely principally on two sources of structural restraints: (i) restraints on backbone conformation from isotropic 15N and 13C chemical shifts, based on empirical correlations between chemical shifts and backbone torsion angles; (ii) restraints on inter-residue proximities from qualitative measurements of internuclear dipole–dipole couplings, detected as the presence or absence of inter-residue crosspeaks in multidimensional spectra. We show that site-specific dipole–dipole couplings among 15N-labeled backbone amide sites and among 13C-labeled backbone carbonyl sites can be measured quantitatively in uniformly-labeled proteins, using dipolar recoupling techniques that we call 15N-BARE and 13C-BARE (BAckbone REcoupling), and that the resulting data represent a new source of restraints on backbone conformation. 15N-BARE and 13C-BARE data can be incorporated into structural modeling calculations as potential energy surfaces, which are derived from comparisons between experimental 15N and 13C signal decay curves, extracted from crosspeak intensities in series of two-dimensional spectra, with numerical simulations of the 15N-BARE and 13C-BARE measurements. We demonstrate this approach through experiments on microcrystalline, uniformly 15N, 13C-labeled protein GB1. Results for GB1 show that 15N-BARE and 13C-BARE restraints are complementary to restraints from chemical shifts and inter-residue crosspeaks, improving both the precision and the accuracy of calculated structures. PMID:22449573

  13. Age-dependent changes in the proteolytic-antiproteolytic balance after alcohol and black tea consumption.

    PubMed

    Augustyniak, A; Bylińska, A; Skrzydlewska, E

    2011-03-01

    Aging is accompanied by changes in the redox balance that is additionally modified by alcohol. Ethanol metabolism is connected with generation of free radicals which can damage cell components especially when antioxidant mechanisms are not able to neutralize them. In connection with the necessity of prevention against oxidative consequences, natural antioxidants are looked for. A natural and commonly used component of the diets with antioxidant properties are teas, especially the black tea. This study provides evidence of the role of black tea in the protection of rat plasma proteins and lipids against oxidative stress caused by aging and ethanol intoxication. For 5 weeks, the rats (2-, 12-, and 24-months old) used for the experiment received a black tea beverage (3 g/l) without or with alcohol (given for 4 weeks). The decrease in antioxidant abilities determined as total antioxidant status during aging and ethanol intoxication resulted in enhanced lipid and protein oxidation (determined as malondialdehyde, carbonyl groups, dityrosine, tryptophan and sulfhydryl groups level). In consequence the decrease in anti-proteases (alpha-1-antitrypsin, alpha-2-macroglobulin) activity and the increase in proteases (elastase and cathepsin G) activity were observed. Black tea protected the plasma antioxidants and prevented oxidative modifications of lipid and protein observed during aging as well as ethanol intoxication. The results indicate that a shift into plasma proteolytic activity results from a decrease in antioxidant abilities, so the use of black tea appears to be beneficial in reducing oxidative stress caused by ethanol and/or aging.

  14. Age-dependent loss of MMP-3 in Hutchinson-Gilford progeria syndrome.

    PubMed

    Harten, Ingrid A; Zahr, Rima S; Lemire, Joan M; Machan, Jason T; Moses, Marsha A; Doiron, Robert J; Curatolo, Adam S; Rothman, Frank G; Wight, Thomas N; Toole, Bryan P; Gordon, Leslie B

    2011-11-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare, progressive segmental premature aging disease that includes scleroderma-like skin, progressive joint contracture, and atherosclerosis. Affected individuals die prematurely of heart attacks or strokes. Extracellular matrix dysregulation is implicated as a factor in disease progression. We analyzed messenger RNA and protein levels for matrix metalloproteinases (MMPs)-2,-3, and -9 in HGPS primary human dermal fibroblasts using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and gelatin zymography. MMP-3 messenger RNA and protein levels decreased significantly with increasing donor age in HGPS fibroblasts but not in controls. MMP-2 messenger RNA also showed a donor age-dependent decrease in HGPS fibroblasts, but levels of secreted protein were unchanged. MMP-9 was similar in HGPS and control cultures. The decreased MMP-3 may represent a shift in the inherent extracellular matrix-degrading proteolytic balance in favor of matrix deposition in HGPS. This metalloproteinase has the potential to serve as a biomarker of therapeutic efficacy when assessing treatments for HGPS.

  15. [Metabolic memory enhances hormesis effect to the copper ions in age-depended manner].

    PubMed

    Bozhkov, A I; Sidorov, V I; Kurguzova, N I; Dlubovskaia, V L

    2014-01-01

    The ability of young and old rats to manifest the hormesis effect to lethal doses of copper sulphate and the ability to save the induced "adaptive" pattern of redistribution of copper ions after the transfer of animals in the standard conditions is the mechanism of metabolic memory. It was found that pretreatment of animals with low-dose (1 mg per 100 g body mass, i.e. 33% of the lethal dose) of copper sulfate induced the formation of their resistance to lethal doses (3 mg per 100 g), so the hormesis effect was manifested. Hormesis effect depended on the number of pre injections of small doses of copper sulphate in an S-shaped manner. The protective effect increased after 1 to 3 of preliminary injections of copper sulfate, and after four or more injections the hormesis effect decreased. It is shown that the cardinal role in intracellular pattern of copper ion redistribution play heat-stable copper binding proteins 12 kDa cytosolic proteins. The formed "adaptive" pattern of intracellular distribution of the copper ions may be reproduced, after at least, one month. The prolonged hormesis effect can be attributed to the forming metabolic memory. The intracellular distribution pattern of the copper ions was age-dependent. Age-related differences were found in hormesis effect induced by copper ions, which results in increased binding capacity of copper binding proteins in old animals, with a higher content of copper ions in the mitochondria and microsomes as compared to young animals. PMID:25051761

  16. Chronic BDNF deficiency leads to an age-dependent impairment in spatial learning.

    PubMed

    Petzold, Anne; Psotta, Laura; Brigadski, Tanja; Endres, Thomas; Lessmann, Volkmar

    2015-04-01

    Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neural plasticity and, consequently, of memory formation. In hippocampus-dependent learning tasks BDNF also seems to play an essential role. However, there are conflicting results concerning the spatial learning ability of aging BDNF(+/-) mice in the Morris water maze paradigm. To evaluate the effect of chronic BDNF deficiency in the hippocampus on spatial learning throughout life, we conducted a comprehensive study to test differently aged BDNF(+/-) mice and their wild type littermates in the Morris water maze and to subsequently quantify their hippocampal BDNF protein levels as well as expression levels of TrkB receptors. We observed an age-dependent learning deficit in BDNF(+/-) animals, starting at seven months of age, despite stable hippocampal BDNF protein expression and continual decline of TrkB receptor expression throughout aging. Furthermore, we detected a positive correlation between hippocampal BDNF protein levels and learning performance during the probe trial in animals that showed a good learning performance during the long-term memory test.

  17. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society.

    PubMed

    Joulan, Karine; Brémond, Roland; Hautière, Nicolas

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  18. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

    PubMed Central

    Joulan, Karine; Brémond, Roland

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  19. Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

    PubMed Central

    2013-01-01

    Background Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development. Methods We carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs. Results This analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling. Conclusions These deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders. PMID:23915542

  20. [Age-dependent changes in mRNA transport (nucleus-cytoplasm)].

    PubMed

    Müller, W E; Agutter, P S; Prochnow, D J; Fasold, H; Sève, A P; Tsiapalis, C M; Schröder, H C

    1993-01-01

    Transport of mRNA from nucleus to cytoplasm is an ATP-dependent process which occurs strictly vectorially. Because the mRNA is structurally bound during transport, mRNA transport is a "solid-state" process consisting of i) mRNA release from the nuclear matrix, ii) mRNA translocation through the nuclear pore, and iii) cytoskeletal binding. We identified and purified the following components involved in the translocation step: i) the nuclear envelope (NE) nucleoside triphosphatase (NTPase) which is stimulated by the 3'poly(A) tail of mRNA, ii) the poly(A)-recognizing mRNA carrier, iii) the NE protein kinase, and iv) the NE phosphatase. In addition, we found that an RNA helicase activity is present in NE, which also may be involved in RNA transport. Our results show that, besides poly(A), also double-stranded RNA structures may modulate RNA export. The amount of mRNA released from nuclei markedly decreases with age. Evidence is presented that this age-dependent change is caused by an impairment of polyadenylation of mRNA, hnRNA processing, release of mRNA from nuclear matrix, and translocations of mRNA from nuclear to cytoplasmic compartment (decrease in activities of NE NTPase, protein kinase, and phosphatase; decrease in poly(A)-binding affinity of mRNA carrier).

  1. Age-dependent changes in rat liver prenyltransferases.

    PubMed

    Thelin, A; Runquist, M; Ericsson, J; Swiezewska, E; Dallner, G

    1994-10-20

    Mevalonate pathway lipids including cholesterol, ubiquinone and dolichol, are of great importance for cellular function. Many of the enzymes of this pathway are thus strictly regulated. During development of the rat, the cellular levels of certain of these lipids vary. Prenyltransferases have been investigated and it is reported here that farnesyl pyrophosphate synthase activity in rat liver cytosol decreases after birth to a lower, steady level. This decrease is not paralleled by the level of synthase protein, which shows two maxima, one immediately after birth and the other 30 days later. cis-Prenyltransferase activity is low after birth, increases continuously up to day-54 and then decreases to a low level which was maintained throughout the remainder of the study (365 days). Squalene synthase exhibits high activity after birth, but decreases during the first 100 days thereafter, and subsequently remains at the low level thus reached. In contrast to these changes in the activities of the prenyltransferases, the level of cholesterol is constant and the dolichol concentration increases continuously throughout the entire period studied.

  2. Protective mechanisms of Cucumis sativus in diabetes-related modelsof oxidative stress and carbonyl stress

    PubMed Central

    Heidari, Himan; Kamalinejad, Mohammad; Noubarani, Maryam; Rahmati, Mokhtar; Jafarian, Iman; Adiban, Hasan; Eskandari, Mohammad Reza

    2016-01-01

    Introduction: Oxidative stress and carbonyl stress have essential mediatory roles in the development of diabetes and its related complications through increasing free radicals production and impairing antioxidant defense systems. Different chemical and natural compounds have been suggested for decreasing such disorders associated with diabetes. The objectives of the present study were to investigate the protective effects of Cucumis sativus (C. sativus) fruit (cucumber) in oxidative and carbonyl stress models. These diabetes-related models with overproduction of reactive oxygen species (ROS) and reactive carbonyl species (RCS) simulate conditions observed in chronic hyperglycemia. Methods: Cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonyl stress model) were measured and the protective effects of C. sativus were evaluated using freshly isolated rat hepatocytes. Results: Aqueous extract of C. sativus fruit (40 μg/mL) prevented all cytotoxicity markers in both the oxidative and carbonyl stress models including cell lysis, ROS formation, membrane lipid peroxidation, depletion of glutathione, mitochondrial membrane potential decline, lysosomal labialization, and proteolysis. The extract also protected hepatocytes from protein carbonylation induced by glyoxal. Our results indicated that C. sativus is able to prevent oxidative stress and carbonyl stress in the isolated hepatocytes. Conclusion: It can be concluded that C. sativus has protective effects in diabetes complications and can be considered a safe and suitable candidate for decreasing the oxidative stress and carbonyl stress that is typically observed in diabetes mellitus. PMID:27340622

  3. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina.

    PubMed

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  4. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

    PubMed Central

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  5. Age-Dependent Changes of Monocarboxylate Transporter 8 Availability in the Postnatal Murine Retina

    PubMed Central

    Henning, Yoshiyuki; Szafranski, Karol

    2016-01-01

    The thyroid hormones (TH) triiodothyronine (T3) and its prohormone thyroxine (T4) are crucial for retinal development and function, and increasing evidence points at TH dysregulation as a cause for retinal degenerative diseases. Thus, precise regulation of retinal TH supply is required for proper retinal function, but knowledge on these mechanisms is still fragmentary. Several transmembrane transporters have been described as key regulators of TH availability in target tissues of which the monocarboxylate transporter 8 (MCT8), a high affinity transporter for T4 and T3, plays an essential role in the central nervous system. Moreover, in the embryonic chicken retina, MCT8 is highly expressed, but the postnatal availability of MCT8 in the mammalian retina was not reported to date. In the present study, spatiotemporal retinal MCT8 availability was examined in mice of different age. For this purpose, we quantified expression levels of Mct8 via Real-Time Reverse-Transcriptase PCR in mouse eyecups (C57BL/6) of juvenile and adult age groups. Additionally, age-dependent MCT8 protein levels were quantified via Western blotting and localized via immunofluorescence confocal microscopy. While no difference in Mct8 expression levels could be detected between age groups, MCT8 protein levels in juvenile animals were about two times higher than in adult animals based on Western blot analyses. Immunohistochemical analyses showed that MCT8 immunoreactivity in the eyecup was restricted to the retina and the retinal pigment epithelium. In juvenile mice, MCT8 was broadly observed along the apical membrane of the retinal pigment epithelium, tightly surrounding photoreceptor outer segments. Distinct immunopositive staining was also detected in the inner nuclear layer and the ganglion cell layer. However, in adult specimens, immunoreactivity visibly declined in all layers, which was in line with Western blot analyses. Since MCT8 was abundantly present in juvenile and about twofold lower in

  6. Effects of low doses of quercetin and genistein on oxidation and carbonylation in hemoglobin and myoglobin.

    PubMed

    Boadi, William Y; Johnson, Damitea

    2014-09-01

    Protein-bound carbonyls have been shown to increase with age as well as in numerous diseases including rheumatoid arthritis, adult respiratory syndrome pulmonary fibrosis, diabetes, Parkinson's disease, and Alzheimer's just to mention a few. The effects of the flavonoids quercetin and genistein were investigated according to their ability to inhibit the oxidation of hemoglobin and myoglobin via the Fenton's pathway. Antioxidative activity of the flavonoids were determined by oxidizing hemoglobin and myoglobin in separate experiments with 50 μM Fe(2+) and 0.01 mM hydrogen peroxide (H2O2) with and without quercetin and/or genistein. The samples were treated singly with either quercetin, genistein, or in combination at concentrations of 1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 μM, respectively, dissolved in dimethyl sulfoxide (DMSO). Samples were then incubated in a water bath at 37°C for 8, 12, and 24 hr, respectively. Levels of carbonylation were assayed by the protein carbonyl assay and the carbonyl levels quantified and expressed per mg of protein. The results indicate that protein carbonyls for samples treated with quercetin or genistein decreased in a dose-dependent manner compared to the controls. That of quercetin compared to genistein was more efficient in reducing the levels of protein carbonylation in hemoglobin and myoglobin, respectively. The combination of both flavonoids did show a gradual decrease in carbonyl compounds for only hemoglobin for all the doses and times tested. The results indicate that both flavonoids at low doses inhibited carbonylation in both hemoglobin and myoglobin and the inhibition may be attributed to the prevention of protein oxidation. PMID:25026201

  7. Vibrational scaling factors for transition metal carbonyls

    NASA Astrophysics Data System (ADS)

    Assefa, M. K.; Devera, J. L.; Brathwaite, A. D.; Mosley, J. D.; Duncan, M. A.

    2015-11-01

    Vibrational frequencies for a selected set of transition metal carbonyl complexes are computed with various forms of density functional theory (B3LYP, BP86, M06, and M06-L), employing several different basis sets. The computed frequencies for the carbonyl stretches are compared to the experimental values obtained from gas phase infrared spectra of isolated neutrals and ions. Recommended carbonyl-stretch scaling factors which are developed vary significantly for different functionals, but there is little variation with basis set. Scaled frequencies compared to experimental spectra for cobalt and tantalum carbonyl cations reveal additional variations in multiplet patterns and relative band intensities for different functionals.

  8. Age-dependent decrease in the hepatic uptake and biliary excretion of ouabain in rats.

    PubMed

    Ohta, M; Kanai, S; Sato, Y; Kitani, K

    1988-03-01

    The biliary excretion of i.v. injected ouabain was examined in male and female Wistar-derived rats in relation to age. The hepatic uptake velocity for ouabain was also determined in isolated hepatocyte preparations obtained from male rats of various ages. Biliary recovery values of ouabain (percent of the dose) were fairly comparable for young male and female rats (3-4 month old). Recovery progressively decreased with age, the first 10-min recoveries at 24 months being about one-third those of respective young values in both sexes. A significant linear relation was demonstrated between the first 10-min recovery (Y, percent of the dose) and rat age (X, month), yielding the relations of Y = 17.75-0.43X for males and Y = 18.99-0.43X for females respectively. Similarly, the initial uptake velocity (Y, nmol/mg/min) for ouabain decreased in a linear fashion with age (X, month), yielding a significant negative correlation (Y = 0.704-0.0021X, r = -0.839, P less than 0.005, N = 21) at an ouabain concentration of 8 microM. Kinetic studies using non-linear regression analysis revealed a significantly lower Vmax value (0.533 +/- 0.041 nmol/mg/min) in old (24-29 months) rats compared to the young (4-4.5 months) value (1.193 +/- 0.105 nmol per mg/min, P less than 0.05), while the affinity constant (Km, microM) did not differ significantly between young and old animals (203.12 +/- 25.42 microM in young rats vs 283.68 +/- 28.90 microM in old rats, mean +/- SE, 0.05 less than P less than 0.1). The results of the present study suggest that the age-dependent decrease in the biliary recovery of i.v. injected ouabain in rats can be largely explained by the decrease with age in the hepatic uptake of ouabain. Furthermore, the results provide further support for our previous thesis that the decrease in the lateral mobility of hepatocyte plasma membrane proteins, as revealed by the fluorescence recovery after photobleaching technique, may play a significant role in the age-dependent

  9. Age-dependent gait abnormalities in mice lacking the Rnf170 gene linked to human autosomal-dominant sensory ataxia.

    PubMed

    Kim, Youngsoo; Kim, Seong Hun; Kim, Kook Hwan; Chae, Sujin; Kim, Chanki; Kim, Jeongjin; Shin, Hee-Sup; Lee, Myung-Shik; Kim, Daesoo

    2015-12-20

    Really interesting new gene (RING) finger protein 170 (RNF170) is an E3 ubiquitin ligase known to mediate ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate receptors (ITPR1). It has recently been demonstrated that a point mutation of RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), which is characterized by an age-dependent increase of walking abnormalities, a rare genetic disorder reported in only two families. Although this mutant allele is known to be dominant, the functional identity thereof has not been clearly established. Here, we generated mice lacking Rnf170 (Rnf170(-/-)) to evaluate the effect of its loss of function in vivo. Remarkably, Rnf170(-/-) mice began to develop gait abnormalities in old age (12 months) in the form of asynchronous stepping between diagonal limb pairs with a fixed step sequence during locomotion, while age-matched wild-type mice showed stable gait patterns using several step sequence repertoires. As reported in ADSA patients, they also showed a reduced sensitivity for proprioception and thermal nociception. Protein blot analysis revealed that the amount of Itpr1 protein was significantly elevated in the cerebellum and spinal cord but intact in the cerebral cortex in Rnf170(-/-) mice. These results suggest that the loss of Rnf170 gene function mediates ADSA-associated phenotypes and this gives insights on the cure of patients with ADSA and other age-dependent walking abnormalities.

  10. Water-Soluble alpha,beta-unsaturated aldehydes of cigarette smoke induce carbonylation of human serum albumin.

    PubMed

    Colombo, Graziano; Aldini, Giancarlo; Orioli, Marica; Giustarini, Daniela; Gornati, Rosalba; Rossi, Ranieri; Colombo, Roberto; Carini, Marina; Milzani, Aldo; Dalle-Donne, Isabella

    2010-03-01

    Cigarette smoking is a major risk factor for developing pulmonary and cardiovascular diseases as well as some forms of cancer. Understanding the mechanisms by which smoking contributes to disease remains a major research focus. Increased levels of carbonylated serum proteins are present in smokers; albumin is the major carbonylated protein in the bronchoalveolar lavage fluid of older smokers. We have investigated the susceptibility of human serum albumin (HSA) to alpha,beta-unsaturated aldehyde-induced carbonylation when exposed to whole-phase cigarette smoke extract (CSE). Fluorescence studies with fluorescent probes showed depletion of HSA Cys34 free thiol and marked decrease of free Lys residues. Spectrophotometric and immunochemical carbonyl assays after carbonyl derivatization with 2,4-dinitrophenylhydrazine revealed the formation of covalent carbonyl adducts. Nanoscale capillary liquid chromatography and electrospray tandem mass spectrometry analysis detected acrolein and crotonaldehyde Michael adducts at Cys34, Lys525, Lys351, and His39 at all the CSE concentrations tested. Lys541 and Lys545 were also found to form a Schiff base with acrolein. The carbonyl scavenger drugs, hydralazine and pyridoxamine, partially prevented CSE-induced HSA carbonylation. Carbonylation of HSA associated with cigarette smoking might result in modifications of its antioxidant properties and transport functions of both endogenous and exogenous compounds.

  11. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    PubMed

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis. PMID:26460946

  12. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

    PubMed

    Chen, Shuang; Brunskill, Eric W; Potter, S Steven; Dexheimer, Phillip J; Salomonis, Nathan; Aronow, Bruce J; Hong, Christian I; Zhang, Tongli; Kopan, Raphael

    2015-10-12

    During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis.

  13. Targeted gene mutation of E2F1 evokes age-dependent synaptic disruption and behavioral deficits.

    PubMed

    Ting, Jenhao H; Marks, David R; Schleidt, Stephanie S; Wu, Joanna N; Zyskind, Jacob W; Lindl, Kathryn A; Blendy, Julie A; Pierce, R Christopher; Jordan-Sciutto, Kelly L

    2014-06-01

    Aberrant expression and activation of the cell cycle protein E2F1 in neurons has been implicated in many neurodegenerative diseases. As a transcription factor regulating G1 to S phase progression in proliferative cells, E2F1 is often up-regulated and activated in models of neuronal death. However, despite its well-studied functions in neuronal death, little is known regarding the role of E2F1 in the mature brain. In this study, we used a combined approach to study the effect of E2F1 gene disruption on mouse behavior and brain biochemistry. We identified significant age-dependent olfactory and memory-related deficits in E2f1 mutant mice. In addition, we found that E2F1 exhibits punctated staining and localizes closely to the synapse. Furthermore, we found a mirroring age-dependent loss of post-synaptic protein-95 in the hippocampus and olfactory bulb as well as a global loss of several other synaptic proteins. Coincidently, E2F1 expression is significantly elevated at the ages, in which behavioral and synaptic perturbations were observed. Finally, we show that deficits in adult neurogenesis persist late in aged E2f1 mutant mice which may partially contribute to the behavior phenotypes. Taken together, our data suggest that the disruption of E2F1 function leads to specific age-dependent behavioral deficits and synaptic perturbations. E2F1 is a transcription factor regulating cell cycle progression and apoptosis. Although E2F1 dysregulation under toxic conditions can lead to neuronal death, little is known about its physiologic activity in the healthy brain. Here, we report significant age-dependent olfactory and memory deficits in mice with dysfunctional E2F1. Coincident with these behavioral changes, we also found age-matched synaptic disruption and persisting reduction in adult neurogenesis. Our study demonstrates that E2F1 contributes to physiologic brain structure and function. PMID:24460902

  14. Surface decorated platinum carbonyl clusters

    NASA Astrophysics Data System (ADS)

    Ciabatti, Iacopo; Femoni, Cristina; Iapalucci, Maria Carmela; Longoni, Giuliano; Zacchini, Stefano; Zarra, Salvatore

    2012-06-01

    Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters.Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters. CCDC 867747 and 867748. For crystallographic data in CIF or other electronic format see DOI: 10.1039/c2nr30400g

  15. Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols.

    PubMed

    Davis, Dexter C; Walker, Katherine L; Hu, Chunhua; Zare, Richard N; Waymouth, Robert M; Dai, Mingji

    2016-08-24

    A palladium-catalyzed cascade carbonylative spirolactonization of hydroxycyclopropanols has been developed to efficiently synthesize oxaspirolactones common to many complex natural products of important therapeutic value. The mild reaction conditions, high atom economy, broad substrate scope, and scalability of this new method were highlighted in expedient total syntheses of the Turkish tobacco natural products α-levantanolide and α-levantenolide in two and four steps, respectively. The hydroxycyclopropanol substrates are readily available in one step via a Kulinkovich reaction of the corresponding lactones. Mechanistic studies utilizing high-resolution electrospray ionization mass spectrometry (ESI-MS) identified several key intermediates in the catalytic cycle, as well as those related to catalyst decomposition and competitive pathways. PMID:27459274

  16. Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling

    PubMed Central

    Yang, Wei; Burkhardt, Britta; Fischer, Luise; Beirow, Maja; Bork, Nadja; Wönne, Eva C.; Wagner, Cornelia; Husen, Bettina; Zeilinger, Katrin; Liu, Liegang; Nussler, Andreas K.

    2015-01-01

    Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID:27004051

  17. Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice.

    PubMed

    Nakashima, Yuya; Ohsawa, Ikuroh; Konishi, Fumiko; Hasegawa, Takashi; Kumamoto, Shoichiro; Suzuki, Yoshihiko; Ohta, Shigeo

    2009-10-30

    Oxidative stress is one of the major causes of age-dependent memory loss and cognitive decline. Cytotoxic aldehydes are derived from lipid peroxides and their accumulation may be responsible for age-dependent neurodegeneration, including Alzheimer's disease. Since aldehyde dehydrogenases detoxify such aldehydes, we constructed transgenic mice with mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity deficiency (DAL101 mice) as an age-dependent dementia model. This model animal is age-dependently progressed by persistent oxidative stress, and thus enables us to investigate foods that prevent dementia. Since Chlorella, a kind of alga, exhibits various anti-oxidative effects, we investigated whether Chlorella has the potential to prevent age-dependent cognitive impairment. We fed Chlorella to DAL101 mice and investigated its effects on oxidative stress and the progression of cognitive decline using the Morris water-maze and object recognition tests. The diet with Chlorella tended to reduce oxidative stress and significantly prevented the decline of cognitive ability, as shown by both methods. Moreover, consumption of Chlorella decreased the number of activated astrocytes in the DAL101 brain. These findings suggest that the prolonged consumption of Chlorella has the potential to prevent the progression of cognitive impairment.

  18. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival.

    PubMed

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E

    2015-05-28

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a "standard" model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors.

  19. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival.

    PubMed

    Christiansen-Jucht, Céline; Erguler, Kamil; Shek, Chee Yan; Basáñez, María-Gloria; Parham, Paul E

    2015-06-01

    Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a "standard" model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors. PMID:26030468

  20. Partial loss of presenilin impairs age-dependent neuronal survival in the cerebral cortex.

    PubMed

    Watanabe, Hirotaka; Iqbal, Minah; Zheng, Jin; Wines-Samuelson, Mary; Shen, Jie

    2014-11-26

    Mutations in the presenilin (PSEN1 and PSEN2) genes are linked to familial Alzheimer's disease (AD) and cause loss of its essential function. Complete inactivation of presenilins in excitatory neurons of the adult mouse cerebral cortex results in progressive memory impairment and age-dependent neurodegeneration, recapitulating key features of AD. In this study, we examine the effects of varying presenilin dosage on cortical neuron survival by generating presenilin-1 conditional knock-out (PS1 cKO) mice carrying two, one, or zero copies of the PS2 gene. We found that PS1 cKO;PS2(+/-) mice at 16 months exhibit marked neurodegeneration in the cerebral cortex with ∼17% reduction of cortical volume and neuron number, as well as astrogliosis and microgliosis compared with ∼50% reduction of cortical volume and neuron number in PS1 cKO;PS2(-/-) mice. Moreover, there are more apoptotic neurons labeled by activated caspase-3 immunoreactivity and TUNEL assay in PS1 cKO;PS2(+/-) mice at 16 months, whereas apoptotic neurons are increased in the PS1 cKO;PS2(-/-) cerebral cortex at 4 months. The accumulation of the C-terminal fragments of the amyloid precursor protein is inversely correlated with PS dosage. Interestingly, levels of PS2 are higher in the cerebral cortex of PS1 cKO mice, suggesting a compensatory upregulation that may provide protection against neurodegeneration in these mice. Together, our findings show that partial to complete loss of presenilin activity causes progressively more severe neurodegeneration in the mouse cerebral cortex during aging, suggesting that impaired presenilin function by PSEN mutations may lead to neurodegeneration and dementia in AD. PMID:25429133

  1. Detection of oxidative stress-induced carbonylation in live mammalian cells.

    PubMed

    Mukherjee, Kamalika; Chio, Tak Ian; Sackett, Dan L; Bane, Susan L

    2015-07-01

    Oxidative stress is often associated with etiology and/or progression of disease conditions, such as cancer, neurodegenerative diseases, and diabetes. At the cellular level, oxidative stress induces carbonylation of biomolecules such as lipids, proteins, and DNA. The presence of carbonyl-containing biomolecules as a hallmark of these diseases provides a suitable target for diagnostic detection. Here, a simple, robust method for detecting cellular aldehydes and ketones in live cells using a fluorophore is presented. A hydrazine-functionalized synthetic fluorophore serves as an efficient nucleophile that rapidly reacts with reactive carbonyls in the cellular milieu. The product thus formed exhibits a wavelength shift in the emission maximum accompanied by an increase in emission intensity. The photochemical characteristics of the fluorophore enable the identification of the fluorophore-conjugated cellular biomolecules in the presence of unreacted dye, eliminating the need for removal of excess fluorophore. Moreover, this fluorophore is found to be nontoxic and is thus appropriate for live cell analysis. Utility of the probe is demonstrated in two cell lines, PC3 and A549. Carbonylation resulting from serum starvation and hydrogen peroxide-induced stress is detected in both cell lines using fluorescence microscopy and a fluorescence plate reader. The fluorescent signal originates from carbonylated proteins and lipids but not from oxidized DNA, and the majority of the fluorescence signal (>60%) is attributed to fluorophore-conjugated lipid oxidation products. This method should be useful for detecting cellular carbonylation in a high-content assay or high-throughput assay format. PMID:25801292

  2. Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer

    PubMed Central

    Wang, Zhiqi; Li, Sai; Cao, Yu; Tian, Xuefei; Zeng, Rong; Liao, Duan-Fang; Cao, Deliang

    2016-01-01

    Oxidative stress has long been known as a pathogenic factor of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), but the effects of secondary carbonyl lesions receive less emphasis. In inflammatory conditions, reactive oxygen species (ROS), such as superoxide anion free radical (O2∙−), hydrogen peroxide (H2O2), and hydroxyl radical (HO∙), are produced at high levels and accumulated to cause oxidative stress (OS). In oxidative status, accumulated ROS can cause protein dysfunction and DNA damage, leading to gene mutations and cell death. Accumulated ROS could also act as chemical messengers to activate signaling pathways, such as NF-κB and p38 MAPK, to affect cell proliferation, differentiation, and apoptosis. More importantly, electrophilic carbonyl compounds produced by lipid peroxidation may function as secondary pathogenic factors, causing further protein and membrane lesions. This may in turn exaggerate oxidative stress, forming a vicious cycle. Electrophilic carbonyls could also cause DNA mutations and breaks, driving malignant progression of UC. The secondary lesions caused by carbonyl compounds may be exceptionally important in the case of host carbonyl defensive system deficit, such as aldo-keto reductase 1B10 deficiency. This review article updates the current understanding of oxidative stress and carbonyl lesions in the development and progression of UC and CAC. PMID:26823956

  3. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2.

    PubMed

    Sreedharan, Jemeen; Neukomm, Lukas J; Brown, Robert H; Freeman, Marc R

    2015-08-17

    The RNA-processing protein TDP-43 is central to the pathogenesis of amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron (MN) disease. TDP-43 is conserved in Drosophila, where it has been the topic of considerable study, but how TDP-43 mutations lead to age-dependent neurodegeneration is unclear and most approaches have not directly examined changes in MN morphology with age. We used a mosaic approach to study age-dependent MN loss in the adult fly leg where it is possible to resolve single motor axons, NMJs and active zones, and perform rapid forward genetic screens. We show that expression of TDP-43(Q331K) caused dying-back of NMJs and axons, which could not be suppressed by mutations that block Wallerian degeneration. We report the identification of three genes that suppress TDP-43 toxicity, including shaggy/GSK3, a known modifier of neurodegeneration. The two additional novel suppressors, hat-trick and xmas-2, function in chromatin modeling and RNA export, two processes recently implicated in human ALS. Loss of shaggy/GSK3, hat-trick, or xmas-2 does not suppress Wallerian degeneration, arguing TDP-43(Q331K)-induced and Wallerian degeneration are genetically distinct processes. In addition to delineating genetic factors that modify TDP-43 toxicity, these results establish the Drosophila adult leg as a valuable new tool for the in vivo study of adult MN phenotypes.

  4. Finding Uncertainties that Cause the Age Dependence of Dose Limits to Be Immature

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2007-01-01

    Space radiation permissible exposure limits (PEL) are intended to set acceptable levels of cancer risks, and avoid any clinical significant non-cancer effects. The 1989 recommendation of the National Council of Radiation Protection and Measurements (NCRP) recommended a strong age dependence of dose limits that departed drastically from the then mature 1970 dose limits recommendations from the National Academy of Science, which were independent of age. In 2000, the NCRP recommended revised limits that showed a similar trend of risk with age to the 1989 report. In this model, the cancer risk per Sv varies by more than 2-fold for ages between 30- and 50-yr. Therefore for galactic cosmic rays exposure, astronaut age has a larger influence on risk then radiation shielding mass or material composition, vehicle propulsion method, or position in the solar cycle. For considering the control of mission costs and resources, the possibility of using astronaut age as a trade variable in mission design could be considered. However, the uncertainties in describing the age dependence on risk have not been fully explored. We discuss biological factors that influence the age dependence of radiation risks, including susceptibility, expression and latency, and radiation quality. These factors depend not only on the individual s age, but also their genetic sensitivity and interaction with other environmental factors. Epidemiological data is limited in describing the age dependence on risk. The 2005, BEIR VII report recommends an age dependence for cancer risk attributable solely to the life-table disagreeing strongly with the NCRP model. However, BEIR VII also noted the limited power of human data for concomitantly describing both age and age after exposure dependences of cancer risks. Many experimental studies have shown that high LET radiation (e.g., high charge and energy (HZE) nuclei and neutrons) display reduced latency compared to low LET radiation, suggesting distinct biological

  5. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    PubMed

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  6. Age-Dependent and Age-Independent Measures of Locus of Control.

    ERIC Educational Resources Information Center

    Sherman, Lawrence W.; Hofmann, Richard

    Using a longitudinal data set obtained from 169 pre-adolescent children between the ages of 8 and 13 years, this study statistically divided locus of control into two independent components. The first component was noted as "age-dependent" (AD) and was determined by predicted values generated by regressing children's ages onto their locus of…

  7. Molecular Correlates of Age-Dependent Seizures in an Inherited Neonatal-Infantile Epilepsy

    ERIC Educational Resources Information Center

    Liao, Yunxiang; Deprez, Liesbet; Maljevic, Snezana; Pitsch, Julika; Claes, Lieve; Hristova, Dimitrina; Jordanova, Albena; Ala-Mello, Sirpa; Bellan-Koch, Astrid; Blazevic, Dragica; Schubert, Simone; Thomas, Evan A.; Petrou, Steven; Becker, Albert J.; De Jonghe, Peter; Lerche, Holger

    2010-01-01

    Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial…

  8. Paradise Lost: Age-Dependent Mortality of American Communes, 1609-1965

    ERIC Educational Resources Information Center

    Kitts, James A.

    2009-01-01

    Theorists agree that the risk of folding changes as organizations age, but there is little consensus as to the general form or generative processes of age-dependent mortality. This article investigates four such processes (maturation, senescence, legitimation and obsolescence), which have been taken as competing accounts. Using two analytical…

  9. Age-dependent changes in the neural substrates of empathy in autism spectrum disorder

    PubMed Central

    Greimel, Ellen; Piefke, Martina; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R.; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2014-01-01

    In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12–31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face’s emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the ‘fine-tuning’ of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms. PMID:23784073

  10. Age-dependent changes in the neural substrates of empathy in autism spectrum disorder.

    PubMed

    Schulte-Rüther, Martin; Greimel, Ellen; Piefke, Martina; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2014-08-01

    In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12-31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face's emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the 'fine-tuning' of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms.

  11. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  12. Ontogenetic changes in genetic variances of age-dependent plasticity along a latitudinal gradient.

    PubMed

    Nilsson-Örtman, V; Rogell, B; Stoks, R; Johansson, F

    2015-10-01

    The expression of phenotypic plasticity may differ among life stages of the same organism. Age-dependent plasticity can be important for adaptation to heterogeneous environments, but this has only recently been recognized. Whether age-dependent plasticity is a common outcome of local adaptation and whether populations harbor genetic variation in this respect remains largely unknown. To answer these questions, we estimated levels of additive genetic variation in age-dependent plasticity in six species of damselflies sampled from 18 populations along a latitudinal gradient spanning 3600 km. We reared full sib larvae at three temperatures and estimated genetic variances in the height and slope of thermal reaction norms of body size at three points in time during ontogeny using random regression. Our data show that most populations harbor genetic variation in growth rate (reaction norm height) in all ontogenetic stages, but only some populations and ontogenetic stages were found to harbor genetic variation in thermal plasticity (reaction norm slope). Genetic variances in reaction norm height differed among species, while genetic variances in reaction norm slope differed among populations. The slope of the ontogenetic trend in genetic variances of both reaction norm height and slope increased with latitude. We propose that differences in genetic variances reflect temporal and spatial variation in the strength and direction of natural selection on growth trajectories and age-dependent plasticity. Selection on age-dependent plasticity may depend on the interaction between temperature seasonality and time constraints associated with variation in life history traits such as generation length. PMID:25649500

  13. Expression of A152T human tau causes age-dependent neuronal dysfunction and loss in transgenic mice.

    PubMed

    Maeda, Sumihiro; Djukic, Biljana; Taneja, Praveen; Yu, Gui-Qiu; Lo, Iris; Davis, Allyson; Craft, Ryan; Guo, Weikun; Wang, Xin; Kim, Daniel; Ponnusamy, Ravikumar; Gill, T Michael; Masliah, Eliezer; Mucke, Lennart

    2016-04-01

    A152T-variant human tau (hTau-A152T) increases risk for tauopathies, including Alzheimer's disease. Comparing mice with regulatable expression of hTau-A152T or wild-type hTau (hTau-WT), we find age-dependent neuronal loss, cognitive impairments, and spontaneous nonconvulsive epileptiform activity primarily in hTau-A152T mice. However, overexpression of either hTau species enhances neuronal responses to electrical stimulation of synaptic inputs and to an epileptogenic chemical. hTau-A152T mice have higher hTau protein/mRNA ratios in brain, suggesting that A152T increases production or decreases clearance of hTau protein. Despite their functional abnormalities, aging hTau-A152T mice show no evidence for accumulation of insoluble tau aggregates, suggesting that their dysfunctions are caused by soluble tau. In human amyloid precursor protein (hAPP) transgenic mice, co-expression of hTau-A152T enhances risk of early death and epileptic activity, suggesting copathogenic interactions between hTau-A152T and amyloid-β peptides or other hAPP metabolites. Thus, the A152T substitution may augment risk for neurodegenerative diseases by increasing hTau protein levels, promoting network hyperexcitability, and synergizing with the adverse effects of other pathogenic factors. PMID:26931567

  14. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain

    SciTech Connect

    Enokido, Yasushi; Yoshitake, Ayaka; Ito, Hikaru; Okazawa, Hitoshi

    2008-11-07

    HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain.

  15. Process and catalyst for carbonylating olefins

    DOEpatents

    Zoeller, J.R.

    1998-06-02

    Disclosed is an improved catalyst system and process for preparing aliphatic carbonyl compounds such as aliphatic carboxylic acids, alkyl esters of aliphatic carboxylic acids and anhydrides of aliphatic carboxylic acids by carbonylating olefins in the presence of a catalyst system comprising (1) a first component selected from at least one Group 6 metal, i.e., chromium, molybdenum, and/or tungsten and (2) a second component selected from at least one of certain halides and tertiary and quaternary compounds of a Group 15 element, i.e., nitrogen, phosphorus and/or arsenic, and (3) as a third component, a polar, aprotic solvent. The process employing the improved catalyst system is carried out under carbonylating conditions of pressure and temperature discussed herein. The process constitutes and improvement over known processes since it can be carried out at moderate carbonylation conditions without the necessity of using an expensive noble metal catalyst, volatile, toxic materials such as nickel tetracarbonyl, formic acid or a formate ester. Further, the addition of a polar, aprotic solvent to the catalyst system significantly increases, or accelerates, the rate at which the carbonylation takes place.

  16. Characteristic infrared intensities of carbonyl stretching vibrations.

    PubMed

    Richter, Wagner E; Silva, Arnaldo F; Vidal, Luciano N; Bruns, Roy E

    2016-07-14

    The experimental infrared fundamental intensities of gas phase carbonyl compounds obtained by the integration of spectral bands in the Pacific Northwest National Laboratory (PNNL) spectral database are in good agreement with the intensities reported by other laboratories having a root mean square error of 27 km mol(-1) or about 13% of the average intensity value. The Quantum Theory of Atoms in Molecules/Charge-Charge Transfer-Counterpolarization (QTAIM/CCTCP) model indicates that the large intensity variation from 61.7 to 415.4 km mol(-1) is largely due to static atomic charge contributions, whereas charge transfer and counterpolarization effects essentially cancel one another leaving only a small net effect. The Characteristic Substituent Shift Model estimates the atomic charge contributions to the carbonyl stretching intensities within 30 km mol(-1) or 10% of the average contribution. However, owing to the size of the 2 × C × CTCP interaction contribution, the total intensities cannot be estimated with this degree of accuracy. The dynamic intensity contributions of the carbon and oxygen atoms account for almost all of the total stretching intensities. These contributions vary over large ranges with the dynamic contributions of carbon being about twice the size of the oxygen ones for a large majority of carbonyls. Although the carbon monoxide molecule has an almost null dipole moment contrary to the very polar bond of the characteristic carbonyl group, its QTAIM/CCTCP model is very similar to those found for the carbonyl compounds. PMID:27306140

  17. Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

    PubMed Central

    Rolyan, Harshvardhan; Tyurina, Yulia Y.; Hernandez, Marylens; Amoscato, Andrew A.; Sparvero, Louis J.; Nmezi, Bruce C.; Lu, Yue; Estécio, Marcos R. H.; Lin, Kevin; Chen, Junda; He, Rong-Rong; Gong, Pin; Rigatti, Lora H.; Dupree, Jeffrey; Bayır, Hülya; Kagan, Valerian E.; Casaccia, Patrizia

    2015-01-01

    Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT Autosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B

  18. Age dependence of the concentrations of harmful substances in Baltic herring (Clupea harengus)

    SciTech Connect

    Perttila, M.; Tervo, V.; Parmanne, R.

    1982-01-01

    The age dependence of Zn, Cu, Pb, Cd, Hg, CH/sub 3/-Hg, DDT, DDD, DDE, HCH, HCB and the PCBs have been studied in Baltic herring of 1 to 6 years of age. Lead, cadmium, mercury and the organochlorine concentrations increase significantly with age. In the case of the DDTs and the PCBs, the variations can be attributed almost totally to the combined effect of age and variations in the lipid percentage.

  19. Optimal Control of Markov Processes with Age-Dependent Transition Rates

    SciTech Connect

    Ghosh, Mrinal K. Saha, Subhamay

    2012-10-15

    We study optimal control of Markov processes with age-dependent transition rates. The control policy is chosen continuously over time based on the state of the process and its age. We study infinite horizon discounted cost and infinite horizon average cost problems. Our approach is via the construction of an equivalent semi-Markov decision process. We characterise the value function and optimal controls for both discounted and average cost cases.

  20. Age-dependent factors in the biokinetics and dosimetry of radionuclides: Proceedings

    SciTech Connect

    Taylor, D.M.; Gerber, G.B.; Stather, J.W.

    1992-12-01

    The need to develop generally accepted models for assessing doses to members of the public has been identified by the International Commission on Radiological Protection which set up in 1987 a Task Group of Committee II on Age-dependent Dosimetry, with the aim of reviewing the current state of knowledge in this area, calculating dose coefficients for different age-groups in the population and identifying the needs for future research. The Radiation Protection Programme of the Commission of the European Communities, the Office of Health and Environmental Research of the United States Department of Energy and the European Late Effects Project Cirpup (EULEP) organised a Workshop on ``Age-dependent Factors in the Biokinetics and Dosimetry of Radionuclides``. This Workshop, which was held at Schloss Elmau in southem Bavaria, Germany, November 4--8 1991, was attended by more than fifty scientists from some fifteen countries. The invited or contributed papers presented at the Workshop, which are published in this volume, covered many areas including gastrointestinal uptake and inhalation of radionuclides by various age-groups in the population, the effect of age on the biokinetics of radionuclides in bone, thyroid and other tissues, the development of age-dependent biokinetic models and the transfer of radionuclides from the mother to the developing embryo and fetus. Reviews of the activities of the ICRP Task Group on Age-dependent Dosimetry and of other collaborative international investigations are also included. The presentations provided a comprehensive overview of the current state of our knowledge on the age-related factors which are of importance for assessing radiation exposure of the population, indicating the progress which has been made since the previous Workshop on this topic held in Angers, France in late 1986.

  1. Age-dependent tissue-specific exposure of cell phone users

    NASA Astrophysics Data System (ADS)

    Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels

    2010-04-01

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  2. Maternal care, mother-offspring aggregation and age-dependent coadaptation in the European earwig.

    PubMed

    Gómez, Y; Kölliker, M

    2013-09-01

    Benefits and costs of parental care are expected to change with offspring development and lead to age-dependent coadaptation expressed as phenotypic (behavioural) matches between offspring age and parental reproductive stage. Parents and offspring interact repeatedly over time for the provision of parental care. Their behaviours should be accordingly adjusted to each other dynamically and adaptively, and the phenotypic match between offspring age and parental stage should stabilize the repeated behavioural interactions. In the European earwig (Forficula auricularia), maternal care is beneficial for offspring survival, but not vital, allowing us to investigate the extent to which the stability of mother-offspring aggregation is shaped by age-dependent coadaptation. In this study, we experimentally cross-fostered nymphs of different age classes (younger or older) between females in early or late reproductive stage to disrupt age-dependent coadaptation, thereby generating female-nymph dyads that were phenotypically matched or mismatched. The results revealed a higher stability in aggregation during the first larval instar when care is most intense, a steeper decline in aggregation tendency over developmental time and a reduced developmental rate in matched compared with mismatched families. Furthermore, nymph survival was positively correlated with female-nymph aggregation stability during the early stages when maternal care is most prevalent. These results support the hypothesis that age-related phenotypically plastic coadaptation affects family dynamics and offspring developmental rate.

  3. Fluorescence of carbonyl-containing intraionic polymethines

    NASA Astrophysics Data System (ADS)

    Kulinich, Andrii V.

    2016-09-01

    Electronic structure and spectral-fluorescent properties of four related indole-based intraionic polymethines are discussed. They all comprise at least one carbonyl group in the acceptor part of their molecule but the effects of the carbonyls upon their UV/Vis and fluorescence spectra depend substantially on its position within the polymethine chromophore. At that, solvation of the carbonyls with highly electrophilic protic solvents can, as a function of dye structure, cause both a rise and decrease of fluorescence quantum yield of a dye or have no tangible effect at all. To get insight into the regularities of such behaviour, the dyes were examined closely using both their absorption and fluorescence spectral data and the (TD) DFT quantum chemical simulation.

  4. Carbonyl compounds indoors in a changing climate

    PubMed Central

    2012-01-01

    Background Formic acid, acetic acid and formaldehyde are important compounds in the indoor environment because of the potential for these acids to degrade calcareous materials (shells, eggs, tiles and geological specimens), paper and corrode or tarnish metals, especially copper and lead. Carbonyl sulfide tarnishes both silver and copper encouraging the formation of surface sulfides. Results Carbonyls are evolved more quickly at higher temperatures likely in the Cartoon Gallery at Knole, an important historic house near Sevenoaks in Kent, England where the study is focused. There is a potential for higher concentrations to accumulate. However, it may well be that in warmer climates they will be depleted more rapidly if ventilation increases. Conclusions Carbonyls are likely to have a greater impact in the future. PMID:22439648

  5. Detection of Oxidative Stress-Induced Carbonylation in Live Mammalian Cells

    PubMed Central

    Mukherjee, Kamalika; Chio, Tak Ian; Sackett, Dan L.; Bane, Susan L.

    2015-01-01

    Oxidative stress is often associated with etiology and/or progression of disease conditions, such as cancer, neurodegenerative diseases, and diabetes. At the cellular level, oxidative stress induces carbonylation of biomolecules such as lipids, proteins and DNA. The presence of carbonylcontaining biomolecules as a hallmark of these diseases provides a suitable target for diagnostic detection. Here, a simple, robust method for detecting cellular aldehydes and ketones in live cells using a fluorophore is presented. A hydrazine-functionalized synthetic fluorophore serves as an efficient nucleophile that rapidly reacts with reactive carbonyls in the cellular milieu. The product thus formed exhibits a wavelength shift in the emission maximum accompanied by an increase in emission intensity. The photochemical characteristics of the fluorophore enable the identification of the fluorophore-conjugated cellular biomolecules in the presence of unreacted dye, eliminating the need for removal of excess fluorophore. Moreover, this fluorophore is found to be non-toxic and is thus appropriate for live cell analysis. Utility of the probe is demonstrated in two cell lines, PC3 and A549. Carbonylation resulting from serum starvation and hydrogen peroxide induced stress is detected in both cell lines using fluorescence microscopy and a fluorescence plate reader. The fluorescent signal originates from carbonylated proteins and lipids but not from oxidized DNA, and the majority of the fluorescence signal (>60%) is attributed to fluorophore-conjugated lipid oxidation products. This method should be useful for detecting cellular carbonylation in a high content assay or high throughput assay format. PMID:25801292

  6. Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent.

    PubMed

    Ryan, D; Koss, D; Porcu, E; Woodcock, H; Robinson, L; Platt, B; Riedel, G

    2013-07-01

    We recently generated an advanced mouse model of Alzheimer's disease (AD) by targeted knock-in of single-copy mutated human amyloid precursor-protein (APP) and tau genes, crossed with a non-symptomatic presenilin (PS1A246E) over-expressing mouse line. These PLB1Triple mice presented with age-dependent and AD-relevant phenotypes. Homozygous PLB1Triple mice aged 4-12 months were assessed here in a battery of spatial learning tasks: Exp.1 radial-arm water maze (spatial reference and working memory) Exp.2 open-field water maze (spatial reference memory); Exp.3 home cage observation system with spatial learning (IntelliCage); Exp.4 spontaneous object recognition (SOR; novel object and spatial object shift). A separate test with high-expression transgenic APP mice matching the design of experiment 1 was also performed. Spatial deficits in PLB1Triple mice were confirmed at 12, but not 4 months in both water maze tasks. PSAPP mice, by contrast, presented with severe yet non-progressive spatial learning deficits already at 4 months. During tests of spatial learning in SOR and IntelliCage, PLB1Triple mice neither acquired the location of the water-rewarded corner, nor recognize novel or spatially shifted objects at 4 months, indicating these protocols to be more sensitive than the water maze. Collectively and in line with AD symptomatology, PLB1Triple mice present with a graded and progressive age-dependent loss of spatial memory that can be revealed by the use of a battery of tasks. With the emergence of subtle deficits progressively increasing in severity, PLB1Triple mice may offer a more patho-physiologically relevant model of dementia than aggressive expression models.

  7. NSP4 elicits age-dependent diarrhea and Ca(2+)mediated I(-) influx into intestinal crypts of CF mice.

    PubMed

    Morris, A P; Scott, J K; Ball, J M; Zeng, C Q; O'Neal, W K; Estes, M K

    1999-08-01

    Homologous disruption of the murine gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) leads to the loss of cAMP-mediated ion transport. Mice carrying this gene defect exhibit meconium ileus at birth and gastrointestinal plugging during the neonatal period, both contributing to high rates of mortality. We investigated whether infectious mammalian rotavirus, the recently characterized rotaviral enterotoxin protein NSP4, or its active NSP4(114-135) peptide, can overcome these gastrointestinal complications in CF (CFTR(m3Bay) null mutation) mice. All three agents elicited diarrhea when administered to wild-type (CFTR(+/+)), heterozygous (CFTR(+/-)), or homozygous (CFTR(-/-)) 7- to 14-day-old mouse pups but were ineffective when given to older mice. The diarrheal response was accompanied by non-age-dependent intracellular Ca(2+) mobilization within both small and large intestinal crypt epithelia. Significantly, NSP4 elicited cellular I(-) influx into intestinal epithelial cells from all three genotypes, whereas both carbachol and the cAMP-mobilizing agonist forskolin failed to evoke influx in the CFTR(-/-) background. This unique plasma membrane halide permeability pathway was age dependent, being observed only in mouse pup crypts, and was abolished by either the removal of bath Ca(2+) or the transport inhibitor DIDS. These findings indicate that NSP4 or its active peptide may induce diarrhea in neonatal mice through the activation of an age- and Ca(2+)-dependent plasma membrane anion permeability distinct from CFTR. Furthermore, these results highlight the potential for developing synthetic analogs of NSP4(114-135) to counteract chronic constipation/obstructive bowel syndrome in CF patients. PMID:10444458

  8. Copper-Catalyzed Carbonylative Coupling of Cycloalkanes and Amides.

    PubMed

    Li, Yahui; Dong, Kaiwu; Zhu, Fengxiang; Wang, Zechao; Wu, Xiao-Feng

    2016-06-13

    Carbonylation reactions are a most powerful method for the synthesis of carbonyl-containing compounds. However, most known carbonylation procedures still require noble-metal catalysts and the use of activated compounds and good nucleophiles as substrates. Herein, we developed a copper-catalyzed carbonylative transformation of cycloalkanes and amides. Imides were prepared in good yields by carbonylation of a C(sp(3) )-H bond of the cycloalkane with the amides acting as weak nucleophiles. Notably, this is the first report of copper-catalyzed carbonylative C-H activation. PMID:27167881

  9. High Pressure Synthesis of Transition Metal Carbonyls.

    ERIC Educational Resources Information Center

    Hagen, A. P.; And Others

    1979-01-01

    Presents an experiment which uses readily available starting materials and inexpensive equipment for synthesis of transition metal carbonyls at 1000 atm and which is intended to give students experience in techniques used in research and industry. Safety precautions are emphasized. (Author/SA)

  10. Organocatalyzed Intramolecular Carbonyl-Ene Reactions.

    PubMed

    Dahlmann, Heidi A; McKinney, Amanda J; Santos, Maria P; Davis, Lindsey O

    2016-05-31

    An organocatalyzed intramolecular carbonyl-ene reaction was developed to produce carbocyclic and heterocyclic 5- and 6-membered rings from a citronellal-derived trifluoroketone and a variety of aldehydes. A phosphoramide derivative was found to promote the cyclization of the trifluoroketone, whereas a less acidic phosphoric acid proved to be a superior catalyst for the aldehyde substrates.

  11. Age-Dependent Terminal Declines in Reproductive Output in a Wild Bird

    PubMed Central

    Hammers, Martijn; Richardson, David S.; Burke, Terry; Komdeur, Jan

    2012-01-01

    In many iteroparous species individual fitness components, such as reproductive output, first increase with age and then decline during late-life. However, individuals differ greatly in reproductive lifespan, but reproductive declines may only occur in the period just before their death as a result of an age-independent decline in physiological condition. To fully understand reproductive senescence it is important to investigate to what extent declines in late-life reproduction can be explained by age, time until death, or both. However, the study of late-life fitness performance in natural populations is challenging as the exact birth and death dates of individuals are often not known, and most individuals succumb to extrinsic mortality before reaching old age. Here, we used an exceptional long-term longitudinal dataset of individuals from a natural, closed, and predator-free population of the Seychelles warbler (Acrocephalus sechellensis) to investigate reproductive output, both in relation to age and to the time until the death of an individual (reverse-age approach). We observed an initial age-dependent increase in reproductive output that was followed by a decline in old age. However, we found no significant decline in reproductive output in the years directly preceding death. Although post-peak reproductive output declined with age, this pattern differed between terminal and non-terminal reproductive attempts, and the age-dependence of the terminal breeding attempt explained much of the variation in age-specific reproductive output. In fact, terminal declines in reproductive output were steeper in very old individuals. These results indicate that not only age-dependent, but also age-independent factors, such as physiological condition, need to be considered to understand reproductive senescence in wild-living animals. PMID:22792307

  12. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    PubMed

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD.

  13. Millimeter wave spectra of carbonyl cyanide ⋆

    PubMed Central

    Bteich, S.B.; Tercero, B.; Cernicharo, J.; Motiyenko, R.A.; Margulès, L.; Guillemin, J.-C.

    2016-01-01

    Context More than 30 cyanide derivatives of simple organic molecules have been detected in the interstellar medium, but only one dicarbonitrile has been found and that very recently. There is still a lack of high-resolution spectroscopic data particularly for dinitriles derivatives. The carbonyl cyanide molecule is a new and interesting candidate for astrophysical detection. It could be formed by the reaction of CO and CN radicals, or by substitution of the hydrogen atom by a cyano group in cyanoformaldehyde, HC(=O)CN, that has already been detected in the interstellar medium. Aims The available data on the rotational spectrum of carbonyl cyanide is limited in terms of quantum number values and frequency range, and does not allow accurate extrapolation of the spectrum into the millimeter-wave range. To provide a firm basis for astrophysical detection of carbonyl cyanide we studied its millimeter-wave spectrum. Methods The rotational spectrum of carbonyl cyanide was measured in the frequency range 152 - 308 GHz and analyzed using Watson’s A- and S-reduction Hamiltonians. Results The ground and first excited state of v5 vibrational mode were assigned and analyzed. More than 1100 distinct frequency lines of the ground state were fitted to produce an accurate set of rotational and centrifugal distortion constants up to the eighth order. The frequency predictions based on these constants should be accurate enough for astrophysical searches in the frequency range up to 500 GHz and for transition involving energy levels with J ≤ 100 and Ka ≤ 42. Based on the results we searched for interstellar carbonyl cyanide in available observational data without success. Thus, we derived upper limits to its column density in different sources. PMID:27738349

  14. Age-dependent loss of the C-terminal amino acid from alpha crystallin

    NASA Technical Reports Server (NTRS)

    Emmons, T.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Antiserum made against the C-terminal region of alpha-A crystallin was used to monitor the purification of a tryptic peptide containing the C-terminus of the molecule from fetal versus adult bovine lenses. Mass spectral analysis of the peptide preparations obtained from these lenses demonstrated the presence of a peptide (T20) containing an intact C-terminus from fetal lenses and the presence of an additional peptide (T20') from older lenses that contained a cleaved C-terminal serine. These results demonstrate an age-dependent processing of alpha-A crystallin in the bovine lens, resulting in removal of the C-terminal amino acid residue.

  15. Large time behavior in a nonlinear age-dependent population dynamics problem with spatial diffusion.

    PubMed

    Langlais, M

    1988-01-01

    In this work we analyze the large time behavior in a nonlinear model of population dynamics with age-dependence and spatial diffusion. We show that when t----+ infinity either the solution of our problem goes to 0 or it stabilizes to a nontrivial stationary solution. We give two typical examples where the stationary solutions can be evaluated upon solving very simple partial differential equations. As a by-product of the extinction case we find a necessary condition for a nontrivial periodic solution to exist. Numerical computations not described below show a rapid stabilization.

  16. Method for conversion of .beta.-hydroxy carbonyl compounds

    DOEpatents

    Lilga, Michael A.; White, James F.; Holladay, Johnathan E.; Zacher, Alan H.; Muzatko, Danielle S.; Orth, Rick J.

    2010-03-30

    A process is disclosed for conversion of salts of .beta.-hydroxy carbonyl compounds forming useful conversion products including, e.g., .alpha.,.beta.-unsaturated carbonyl compounds and/or salts of .alpha.,.beta.-unsaturated carbonyl compounds. Conversion products find use, e.g., as feedstock and/or end-use chemicals.

  17. Transition-Metal-Catalyzed Carbonylation of Methyl Acetate.

    ERIC Educational Resources Information Center

    Polichnowski, S. W.

    1986-01-01

    Presents a study of the rhodium-catalyzed, ioding-promoted carbonylation of methyl acetate. This study provides an interesting contrast between the carbonylation of methyl acetate and the carbonylation of methanol when similar rhodium/iodine catalyst systems are used. (JN)

  18. Detoxification of Carbonyl Compounds by Carbonyl Reductase in Neurodegeneration.

    PubMed

    Rashid, Mohammad Abdur; Haque, Mahmuda; Akbar, Mohammed

    2016-01-01

    Oxidative stress in the brain is the major cause of neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases or amyotrophic lateral sclerosis. Under conditions of oxidative stress, the production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, resulting in the modification of macromolecules and their deposition in neuronal cell tissues. ROS plays an important role in neuronal cell death that they generate reactive aldehydes from membrane lipid peroxidation. Several neuronal diseases are associated with increased accumulation of abnormal protein adducts of reactive aldehydes, which mediate oxidative stress-linked pathological events, including cell growth inhibition and apoptosis induction. Combining findings on neurodegeneration and oxidative stress in Drosophila with studies on the metabolic characteristics of the human enzyme CBR1, it is clear now that CBR1 has a potential physiological role of neuroprotection in humans. Several studies suggest that CBR1 represents a significant pathway for the detoxification of reactive aldehydes derived from lipid peroxidation and that CBR1 in humans is essential for neuronal cell survival and to confer protection against oxidative stress-induced brain degeneration. Recently, it was discovered that HIF1alpha, AP-1, and Nrf2 could all regulate CBR1 at the transcriptional level. Nrf2 is known to regulate the transcription of antioxidant enzymes, and CBR1 functions as an antioxidant enzyme, suggesting that transcriptional regulation of CBR1 is a major contributor to the control of oxidative stress in neurodegeneration. PMID:27651263

  19. Age-dependent changes in cuticular hydrocarbons of larvae in Aldrichina grahami (Aldrich) (Diptera: Calliphoridae).

    PubMed

    Xu, Hong; Ye, Gong-Yin; Xu, Ying; Hu, Cui; Zhu, Guang-Hui

    2014-09-01

    Necrophagous flies, comprising the first wave of insects present in a cadaver, provide a great potential for more accurate determination of the late postmortem interval (PMI) based on their age. Cuticular hydrocarbons (CHs) are a promising age indicator in some insect species, especially for the larvae of necrophagous flies. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used to characterize the age-dependent, quantitative changes in CHs of larval Aldrichina grahami (Aldrich) (Diptera: Calliphoridae) at 24°C. The majority of low-molecular-weight alkanes (≤C25) and almost all of the alkenes decreased in abundance with larval development. By contrast, the abundance of high-molecular-weight alkanes of chain length greater than C25 gradually increased with age. For several peaks, including peak 28 (pentacosene a), peak 31 (n-C25), peak 43 (n-C27) and peak 68 (n-C31), a highly significant correlation was found between peak ratio (n-C29 divided by each chromatographic peak) and chronological age of the larvae. A mathematical model, derived from multivariate linear regression analysis, was developed for determining age of the larvae based on age-dependent changes in CHs. The estimated larval age based on the CHs had a good linear correlation with the chronological age (R(2)>0.9). These results indicate that CHs has a great potential for determining the age of fly larvae, and concomitantly for the PMI in forensic investigation.

  20. Altered connexin 43 expression underlies age dependent decrease of Treg cell suppressor function in NOD mice

    PubMed Central

    Kuczma, Michal; Wang, Cong-Yi; Ignatowicz, Leszek; Gourdie, Robert; Kraj, Piotr

    2015-01-01

    Type I diabetes (T1D) is one of the most extensively studied autoimmune diseases but the cellular and molecular mechanisms leading to T cell-mediated destruction of insulin-producing β-cells are still not well understood. Here we show that Treg cells in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate Treg cells in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory functions can be corrected, even in T cells isolated from aged, diabetic mice, by a synergistic activity of retinoic acid, TGF-β, and IL-2, which enhance connexin 43 and Foxp3 expression in Treg cells and restore the ability of conventional CD4+ T cells to upregulate Foxp3 and generate peripherally derived Treg cells. Moreover, we demonstrate that suppression mediated by Treg cells from diabetic mice is enhanced by a novel reagent, which facilitates gap junction aggregation. In summary, our report identifies gap junction-mediated intercellular communication as an important component of the Treg cell suppression mechanism compromised in NOD mice and suggests how Treg mediated immune regulation can be improved. PMID:25911751

  1. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

  2. Reactive Carbonyl Species In Vivo: Generation and Dual Biological Effects

    PubMed Central

    Semchyshyn, Halyna M.

    2014-01-01

    Reactive carbonyls are widespread species in living organisms and mainly known for their damaging effects. The most abundant reactive carbonyl species (RCS) are derived from oxidation of carbohydrates, lipids, and amino acids. Chemical modification of proteins, nucleic acids, and aminophospholipids by RCS results in cytotoxicity and mutagenicity. In addition to their direct toxicity, modification of biomolecules by RCS gives rise to a multitude of adducts and cross links that are increasingly implicated in aging and pathology of a wide range of human diseases. Understanding of the relationship between metabolism of RCS and the development of pathological disorders and diseases may help to develop effective approaches to prevent a number of disorders and diseases. On the other hand, constant persistence of RCS in cells suggests that they perform some useful role in living organisms. The most beneficial effects of RCS are their establishment as regulators of cell signal transduction and gene expression. Since RCS can modulate different biological processes, new tools are required to decipher the precise mechanisms underlying dual effects of RCS. PMID:24634611

  3. C1-C14 carbonyls in Los Angeles air

    SciTech Connect

    Grosjean, E.; Grosjean, D.; Fraser, M.; Cass, G.R.

    1995-12-01

    Air samples collected at five Los Angeles locations have been analyzed for carbonyls as their DNPH derivatives using liquid chromatography and chemical ionization mass spectrometry. Twenty-three carbonyls have been measured: 14 aliphatic aldehydes (from formaldehyde to tetradecanal); 2 aromatics (benzaldehyde and m-tolualdehyde), 3 ketones (acetone, 2-butanone and cyclohexanone), one unsaturated carbonyl (crotonaldehyde) and 3 dicarbonyls (glyoxal, methylglyoxal and biacetyl). Another nineteen carbonyls have been tentatively identified including four high MW (C{sub 15}-C{sub 18}) aliphatic carbonyls.

  4. Oxidative carbonylation of styrene to methyl cinnamate

    SciTech Connect

    Hsu, C.Y.

    1987-04-01

    Oxidative carbonylation technology is used for making methyl cinnamate from styrene as an alternative to Claisen condensation of benzaldehyde with methyl acetate. Using this approach, the optimum yield of cinnamate is greater than 90%, with CO{sub 2}, acetophenone, and phenylsuccinate as the major by-products. The conversion of styrene and the selectivity to cinnamate depend upon the types of catalysts and reaction conditions used. A plausible reaction mechanism is proposed to account for the selective formation of cinnamate.

  5. Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders.

    PubMed

    Graziotto, John J; Cao, Kan; Collins, Francis S; Krainc, Dimitri

    2012-01-01

    While rapamycin has been in use for years in transplant patients as an antirejection drug, more recently it has shown promise in treating diseases of aging, such as neurodegenerative disorders and atherosclerosis. We recently reported that rapamycin reverses the cellular phenotype of fibroblasts from children with the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). We found that the causative aberrant protein, progerin, was cleared through autophagic mechanisms when the cells were treated with rapamycin, suggesting a new potential treatment for HGPS. Recent evidence shows that progerin is also present in aged tissues of healthy individuals, suggesting that progerin may contribute to physiological aging. While it is intriguing to speculate that rapamycin may affect normal aging in humans, as it does in lower organisms, it will be important to identify safer analogues of rapamycin for chronic treatments in humans in order to minimize toxicity. In addition to its role in HGPS and normal aging, we discuss the potential of rapamycin for the treatment of age-dependent neurodegenerative diseases.

  6. Knock-out of ferritin AtFer1 causes earlier onset of age-dependent leaf senescence in Arabidopsis.

    PubMed

    Murgia, Irene; Vazzola, Valentina; Tarantino, Delia; Cellier, Françoise; Ravet, Karl; Briat, Jean-Francois; Soave, Carlo

    2007-12-01

    Ferritins are iron-storage proteins involved in the regulation of free iron levels in the cells. Arabidopsis thaliana AtFer1 ferritin, one of the best characterized plant ferritin isoforms to date, strongly accumulates upon treatment with excess iron, via a nitric oxide-mediated pathway. However other environmental factors, such as exposure to oxidative stress or to pathogen attack, as well as developmental factors regulate AtFer1 transcript levels. In particular, recent findings have highlighted an accumulation of the ferritin transcript during senescence. To investigate the physiological relevance of AtFer1 ferritin during senescence we isolated an Arabidopsis mutant knock-out in the AtFer1 gene, which we named atfer1-2. We analyzed it together with a second, independent AtFer1 KO mutant, the atfer1-1 mutant. Interestingly, both atfer1-1 and atfer1-2 mutants show symptoms of accelerated natural senescence; the precocious leaf yellowing is accompanied by accelerated decrease of maximal photochemical efficiency and chlorophyll degradation. However, no accelerated senescence upon dark treatment was observed in the atfer1 mutants with respect to their wt. These results suggest that AtFer1 ferritin isoform is functionally involved in events leading to the onset of age-dependent senescence in Arabidopsis and that its iron-detoxification function during senescence is required when reactive oxygen species accumulate.

  7. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  8. Cerebrospinal Fluid Extracellular Vesicles Undergo Age Dependent Declines and Contain Known and Novel Non-coding RNAs

    PubMed Central

    Tietje, Ashlee; Maron, Kourtney N.; Wei, Yanzhang; Feliciano, David M.

    2014-01-01

    Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development. PMID:25420022

  9. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  10. Carbonyl compounds generated from electronic cigarettes.

    PubMed

    Bekki, Kanae; Uchiyama, Shigehisa; Ohta, Kazushi; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki

    2014-10-28

    Electronic cigarettes (e-cigarettes) are advertised as being safer than tobacco cigarettes products as the chemical compounds inhaled from e-cigarettes are believed to be fewer and less toxic than those from tobacco cigarettes. Therefore, continuous careful monitoring and risk management of e-cigarettes should be implemented, with the aim of protecting and promoting public health worldwide. Moreover, basic scientific data are required for the regulation of e-cigarette. To date, there have been reports of many hazardous chemical compounds generated from e-cigarettes, particularly carbonyl compounds such as formaldehyde, acetaldehyde, acrolein, and glyoxal, which are often found in e-cigarette aerosols. These carbonyl compounds are incidentally generated by the oxidation of e-liquid (liquid in e-cigarette; glycerol and glycols) when the liquid comes in contact with the heated nichrome wire. The compositions and concentrations of these compounds vary depending on the type of e-liquid and the battery voltage. In some cases, extremely high concentrations of these carbonyl compounds are generated, and may contribute to various health effects. Suppliers, risk management organizations, and users of e-cigarettes should be aware of this phenomenon.

  11. White LED compared with other light sources: age-dependent photobiological effects and parameters for evaluation.

    PubMed

    Rebec, Katja Malovrh; Klanjšek-Gunde, Marta; Bizjak, Grega; Kobav, Matej B

    2015-01-01

    Ergonomic science at work and living places should appraise human factors concerning the photobiological effects of lighting. Thorough knowledge on this subject has been gained in the past; however, few attempts have been made to propose suitable evaluation parameters. The blue light hazard and its influence on melatonin secretion in age-dependent observers is considered in this paper and parameters for its evaluation are proposed. New parameters were applied to analyse the effects of white light-emitting diode (LED) light sources and to compare them with the currently applied light sources. The photobiological effects of light sources with the same illuminance but different spectral power distribution were determined for healthy 4-76-year-old observers. The suitability of new parameters is discussed. Correlated colour temperature, the only parameter currently used to assess photobiological effects, is evaluated and compared to new parameters. PMID:26647954

  12. Age-dependent accumulation of (137)Cs by pike Esox lucius in the Yenisei River.

    PubMed

    Zotina, T A; Trofimova, E A; Dementyev, D V; Bolsunovsky, A Ya

    2016-05-01

    Age-dependent accumulation of (137)Cs in the muscles and bodies of the pike Esox lucius (aged two to seven years) inhabiting a section of the Yenisei River polluted with artificial radionuclides has been studied. The content of (137)Cs in muscles varied from 0.5 to 7.0 Bq/kg of fresh weight. The maximum content of the radionuclide has been found in juveniles. The content of (137)Cs in pike muscles and body decreased considerably with age. The high content of (137)Cs in the muscles of juveniles is probably a consequence of their higher intensity of feeding as compared to older individuals, which is due to the intense growth of juveniles. PMID:27411826

  13. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs. PMID:26796220

  14. Age-dependent branching processes for surveillance of vaccine-preventable diseases with incubation period.

    PubMed

    Slavtchova-Bojkova, Maroussia N; González, Miguel; Martìnez, Rodrigo

    2010-01-01

    The purpose of this paper is to review the recent results of the authors in the area of infectious disease modeling by means of branching stochastic processes. This is a new approach involving age-dependent branching models, which turned out to be more appropriate and flexible for describing the spread of an infection in a given population, than discrete time ones. Concretely, Bellman-Harris and Sevast'yanov's branching processes are investigated. It is justified that the proposed models are proper candidates as models of infectious diseases with incubation period like measles, mumps, avian flu, etc. It is worth to notice that in general the developed methodology is applicable to the diseases that follow the so-called SIR (susceptible-infected-removed) scheme in terms of epidemiological models. Two policies of extra-vaccination level are proposed and compared on the ground of simulation examples. PMID:21423438

  15. Age-dependent changes in cat masseter nerve: an electrophysiological and morphological study.

    PubMed

    Chase, M H; Engelhardt, J K; Adinolfi, A M; Chirwa, S S

    1992-07-24

    The present study was undertaken to determine the manner in which aging affects the function and structure of the masseter nerve in old cats. Electrophysiological data demonstrated a significant decrease in the conduction velocity of the action potential in old cats compared with that observed in adult cats. Light microscopic analyses revealed an age-dependent decrease in axon diameter. Electron microscopic observations of the masseter nerve in the aged cats revealed a disruption of the myelin sheaths and a pronounced increase in collagen fibers in the endoneurium and perineurium. These morphological changes are discussed and then related to the decrease in conduction velocity which was observed in the electrophysiological portion of this study. PMID:1521161

  16. Calculating excess risk with age-dependent adjustment factors and cumulative doses: ethylene oxide case study.

    PubMed

    Sielken, Robert L; Flores, Ciriaco Valdez

    2009-10-01

    U.S. EPA's Supplemental Guidance in 2005 documented their procedure for incorporating age-dependent adjustment factors (ADAFs) into lifetime excess risk calculations. EPA's first attempt to implement an ADAF when the dose-response model had a cumulative dose metric was for ethylene oxide and that attempt (US EPA, 2006) failed to successfully follow EPA's own guidelines. The failure suggested that the incorporation of ADAFs would increase the lifetime excess risk for ethylene oxide by approximately 66%. However, if the procedure in the guidelines were followed correctly, then the increase would have only been 0.008% or approximately 8,000 fold less. Because cumulative exposure is a common dose metric in dose-response models of epidemiological data, a correct implementation of the guidelines is of widespread importance.

  17. Age-Dependent Susceptibility of Chromosome Cohesion to Premature Separase Activation in Mouse Oocytes1

    PubMed Central

    Chiang, Teresa; Schultz, Richard M.; Lampson, Michael A.

    2011-01-01

    ABSTRACT A hypothesis to explain the maternal age-dependent increase in formation of aneuploid eggs is deterioration of chromosome cohesion. Although several lines of evidence are consistent with this hypothesis, whether cohesion is actually reduced in naturally aged oocytes has not been directly tested by any experimental perturbation. To directly target cohesion, we increased the activity of separase, the protease that cleaves the meiotic cohesin REC8, in oocytes. We show that cohesion is more susceptible to premature separase activation in old oocytes than in young oocytes, demonstrating that cohesion is significantly reduced. Furthermore, cohesion is protected by two independent mechanisms that inhibit separase, securin and an inhibitory phosphorylation of separase by CDK1; both mechanisms must be disrupted to prematurely activate separase. With the continual loss of cohesins from chromosomes that occurs throughout the natural reproductive lifespan, tight regulation of separase in oocytes may be particularly important to maintain cohesion and prevent aneuploidy. PMID:21865557

  18. An age-dependent model to analyse the evolutionary stability of bacterial quorum sensing.

    PubMed

    Mund, A; Kuttler, C; Pérez-Velázquez, J; Hense, B A

    2016-09-21

    Bacterial communication is enabled through the collective release and sensing of signalling molecules in a process called quorum sensing. Cooperative processes can easily be destabilized by the appearance of cheaters, who contribute little or nothing at all to the production of common goods. This especially applies for planktonic cultures. In this study, we analyse the dynamics of bacterial quorum sensing and its evolutionary stability under two levels of cooperation, namely signal and enzyme production. The model accounts for mutation rates and switches between planktonic and biofilm state of growth. We present a mathematical approach to model these dynamics using age-dependent colony models. We explore the conditions under which cooperation is stable and find that spatial structuring can lead to long-term scenarios such as coexistence or bistability, depending on the non-linear combination of different parameters like death rates and production costs.

  19. Age-dependent improvement in passive avoidance learning of the young chick: cholinergic mediation?

    PubMed

    Zolman, J F; Mattingly, B A

    1982-06-01

    Cholinergic mediation of the age-dependent improvement in response suppression of the young chick was studied by determining the performance of 4-day-old chicks, pretreated with scopolamine, during passive avoidance (PA) and extinction testing. In Experiment 1, chicks were trained briefly to key peck for heat reward (prepunishment training), and then tested for PA learning under immediate, 2-sec-delayed, or no shock condition. Half of the chicks in each wing-shock (5 mA, 5 sec) condition received saline injections before prepunishment training and .5 mg/kg scopolamine injections after prepunishment training. The rest of the chicks received .5 mg/kg scopolamine injections both before and after prepunishment training. For chicks in both scopolamine groups, delaying shock onset resulted in significantly less response suppression than immediate response-contingent shock. In Experiment 2, 4-day-old chicks injected with either saline or scopolamine were trained to key peck for heat reward and then tested for resistance to extinction under either response-contingent shock or nonshock conditions. Punishment decreased the number of extinction responses for both saline and scopolamine groups of chicks. Previous studies have shown that normal 1-day-old chicks do not show a significant delay of punishment effect during PA testing and that response-contingent punishment increases the number of their responses during extinction. Hence, the results of the present experiments indicate that the age-dependent improvement in response suppression of the young chick cannot be explained solely by a significant increase in central cholinergic functioning. PMID:7096681

  20. Age-Dependent Speciation Can Explain the Shape of Empirical Phylogenies

    PubMed Central

    Hagen, Oskar; Hartmann, Klaas; Steel, Mike; Stadler, Tanja

    2015-01-01

    Tens of thousands of phylogenetic trees, describing the evolutionary relationships between hundreds of thousands of taxa, are readily obtainable from various databases. From such trees, inferences can be made about the underlying macroevolutionary processes, yet remarkably these processes are still poorly understood. Simple and widely used evolutionary null models are problematic: Empirical trees show very different imbalance between the sizes of the daughter clades of ancestral taxa compared to what models predict. Obtaining a simple evolutionary model that is both biologically plausible and produces the imbalance seen in empirical trees is a challenging problem, to which none of the existing models provide a satisfying answer. Here we propose a simple, biologically plausible macroevolutionary model in which the rate of speciation decreases with species age, whereas extinction rates can vary quite generally. We show that this model provides a remarkable fit to the thousands of trees stored in the online database TreeBase. The biological motivation for the identified age-dependent speciation process may be that recently evolved taxa often colonize new regions or niches and may initially experience little competition. These new taxa are thus more likely to give rise to further new taxa than a taxon that has remained largely unchanged and is, therefore, well adapted to its niche. We show that age-dependent speciation may also be the result of different within-species populations following the same laws of lineage splitting to produce new species. As the fit of our model to the tree database shows, this simple biological motivation provides an explanation for a long standing problem in macroevolution. PMID:25575504

  1. Lung injury after hemorrhage is age-dependent: role of peroxisome proliferator activated receptor γ

    PubMed Central

    Zingarelli, Basilia; Hake, Paul W.; O’Connor, Michael; Burroughs, Timothy J.; Wong, Hector R.; Solomkin, Joseph S.; Lentsch, Alex B.

    2009-01-01

    Objective The incidence of multiple organ failure in pediatric trauma victims is lower than in the adult population. However, the molecular mechanisms are not yet defined. We investigated whether the pathophysiologic characteristics of hemorrhage-induced lung injury may be age-dependent and may be regulated by the peroxisome proliferator activator receptor γ (PPARγ). Design Prospective, laboratory investigation that used an established rodent model of hemorrhagic shock. Setting University hospital laboratory. Subjects Young (n=67; 3–5 months old) and mature (n=66; 11–13 months old) male rats. Interventions Hemorrhagic shock was induced in young and mature rats by withdrawing blood to a mean arterial blood pressure of 50 mmHg. After 3 hrs, rats were rapidly resuscitated by infusing the shed blood and sacrificed 3 hrs thereafter. Measurements and Main Results In young rats, lung injury was characterized by accumulation of red cells and neutrophils at the end of the resuscitation period; at Western blot analysis, lung expression of intercellular adhesion molecule-1 (ICAM-1) was increased. In contrast, the severity of lung injury was more pronounced in mature rats. Lung myeloperoxidase activity and expression of constitutive and inducible ICAM-1 was significantly higher in mature rats when compared to young rats. Mature rats also had higher plasma levels of cytokines and chemokines when compared to young rats. This heightened inflammation was associated with higher degree of activation of nuclear factor-κB and down-regulation of PPARγ and heat shock factor-1 in the lung of mature rats when compared to young rats. Treatment with the PPARγ ligand, the cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2, ameliorated lung injury in young, but not in mature animals. Conclusions Lung injury after severe hemorrhage is age-dependent and may be secondary to a diverse regulation of PPARγ. PMID:19384226

  2. Millimeter wave spectra of carbonyl cyanide

    NASA Astrophysics Data System (ADS)

    Bteich, S. B.; Tercero, B.; Cernicharo, J.; Motiyenko, R. A.; Margulès, L.; Guillemin, J.-C.

    2016-07-01

    Context. More than 30 cyanide derivatives of simple organic molecules have been detected in the interstellar medium, but only one dicarbonitrile has been found and that very recently. There is still a lack of high-resolution spectroscopic data particularly for dinitriles derivatives. The carbonyl cyanide molecule is a new and interesting candidate for astrophysical detection. It could be formed by the reaction of CO and CN radicals, or by substitution of the hydrogen atom by a cyano group in cyanoformaldehyde, HC(=O)CN, that has already been detected in the interstellar medium. Aims: The available data on the rotational spectrum of carbonyl cyanide is limited in terms of quantum number values and frequency range, and does not allow accurate extrapolation of the spectrum into the millimeter-wave range. To provide a firm basis for astrophysical detection of carbonyl cyanide we studied its millimeter-wave spectrum. Methods: The rotational spectrum of carbonyl cyanide was measured in the frequency range 152-308 GHz and analyzed using Watson's A- and S-reduction Hamiltonians. Results: The ground and first excited state of v5 vibrational mode were assigned and analyzed. More than 1100 distinct frequency lines of the ground state were fitted to produce an accurate set of rotational and centrifugal distortion constants up to the eighth order. The frequency predictions based on these constants should be accurate enough for astrophysical searches in the frequency range up to 500 GHz and for transition involving energy levels with J ≤ 100 and Ka ≤ 42. Based on the results we searched for interstellar carbonyl cyanide in available observational data without success. Thus, we derived upper limits to its column density in different sources. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2011.0.00009.SV. ALMA is a partnership of ESO (representing its member states), NSF (USA), and NINS (Japan) with NRC (Canada), NSC, and ASIAA (Taiwan), and KASI (Republic of

  3. Carbonyl Emissions from Gasoline and Diesel Motor Vehicles

    SciTech Connect

    Destaillats, Hugo; Jakober, Chris A.; Robert, Michael A.; Riddle, Sarah G.; Destaillats, Hugo; Charles, M. Judith; Green, Peter G.; Kleeman, Michael J.

    2007-12-01

    Carbonyls from gasoline powered light-duty vehicles (LDVs) and heavy-duty diesel powered vehicles (HDDVs) operated on chassis dynamometers were measured using an annular denuder-quartz filter-polyurethane foam sampler with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine derivatization and chromatography-mass spectrometry analyses. Two internal standards were utilized based on carbonyl recovery, 4-fluorobenzaldehyde forcarbonyls and 6-fluoro-4-chromanone for>_C8 compounds. Gas- and particle-phase emissions for 39 aliphatic and 20 aromatic carbonyls ranged from 0.1 ? 2000 ?g/L fuel for LDVs and 1.8 - 27000 mu g/L fuel for HDDVs. Gas-phase species accounted for 81-95percent of the total carbonyls from LDVs and 86-88percent from HDDVs. Particulate carbonyls emitted from a HDDV under realistic driving conditions were similar to concentrations measured in a diesel particulate matter (PM) standard reference material. Carbonyls accounted for 19percent of particulate organic carbon (POC) emissions from low-emission LDVs and 37percent of POC emissions from three-way catalyst equipped LDVs. This identifies carbonyls as one of the largest classes of compounds in LDV PM emissions. The carbonyl fraction of HDDV POC was lower, 3.3-3.9percent depending upon operational conditions. Partitioning analysis indicates the carbonyls had not achieved equilibrium between the gas- and particle-phase under the dilution factors of 126-584 used in the current study.

  4. Carbonyl emissions from gasoline and diesel motor vehicles.

    PubMed

    Jakober, Chris A; Robert, Michael A; Riddle, Sarah G; Destaillats, Hugo; Charles, M Judith; Green, Peter G; Kleeman, Michael J

    2008-07-01

    Carbonyls from gasoline-powered light-duty vehicles (LDVs) and heavy-duty diesel-powered vehicles (HDDVs) operated on chassis dynamometers were measured by use of an annular denuder-quartz filter-polyurethane foam sampler with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine derivatization and chromatography-mass spectrometry analyses. Two internal standards were utilized based on carbonyl recovery: 4-fluorobenzaldehyde for < C8 carbonyls and 6-fluoro-4-chromanone for > or = C8 compounds. Gas- and particle-phase emissions for 39 aliphatic and 20 aromatic carbonyls ranged from 0.1 to 2000 microg/L of fuel for LDVs and from 1.8 to 27 000 microg/L of fuel for HDDVs. Gas-phase species accounted for 81-95% of the total carbonyls from LDVs and 86-88% from HDDVs. Particulate carbonyls emitted from a HDDV under realistic driving conditions were similar to concentrations measured in a diesel particulate matter (PM) standard reference material. Carbonyls accounted for 19% of particulate organic carbon (POC) emissions from low-emission LDVs and 37% of POC emissions from three-way catalyst-equipped LDVs. This identifies carbonyls as one of the largest classes of compounds in LDV PM emissions. The carbonyl fraction of HDDV POC was lower, 3.3-3.9% depending upon operational conditions. Partitioning analysis indicates the carbonyls had not achieved equilibrium between the gas and particle phases under the dilution factors of 126-584 used in the present study.

  5. Antiatherogenic effect of bisvanillyl-hydralazone, a new hydralazine derivative with antioxidant, carbonyl scavenger, and antiapoptotic properties.

    PubMed

    Bouguerne, Benaissa; Belkheiri, Nadji; Bedos-Belval, Florence; Vindis, Cécile; Uchida, Koji; Duran, Hubert; Grazide, Marie-Hélène; Baltas, Michel; Salvayre, Robert; Nègre-Salvayre, Anne

    2011-06-01

    Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but only moderate antioxidant activity, so that high concentrations are required for inhibiting LDL oxidation. We aimed to develop agents sharing both antioxidant and carbonyl scavenger properties. We have synthesized a new hydralazine derivative, the bisvanillyl-hydralazone (BVH). BVH strongly inhibited LDL oxidation induced by copper and by human endothelial cells (HMEC-1), and prevented the formation of macrophagic foam cells. BVH reduced both the extracellular generation of ROS (superoxide anion and hydrogen peroxide) induced by oxidized LDL (oxLDL), as well as intracellular oxidative stress and proteasome activation, NFkappaB activation, and oxLDL-mediated proinflammatory signaling. In parallel, BVH prevented the carbonyl stress induced by oxLDL on cellular proteins, and blocked the apoptotic cascade as assessed by the inhibition of Bid cleavage, cytochrome C release, and DEVDase activation. Lastly, BVH prevented atherogenesis and carbonyl stress in apoE(-/-) mice. In conclusion, BVH is the prototype of a new class of antioxidant and carbonyl scavenger agents designed for new therapeutical approaches in atherosclerosis.

  6. Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men

    PubMed Central

    Konopka, Adam R.; Undem, Miranda K.; Hinkley, James M.; Minchev, Kiril; Kaminsky, Leonard A.; Trappe, Todd A.; Trappe, Scott

    2012-01-01

    To examine potential age-specific adaptations in skeletal muscle size and myofiber contractile physiology in response to aerobic exercise, seven young (YM; 20 ± 1 yr) and six older men (OM; 74 ± 3 yr) performed 12 wk of cycle ergometer training. Muscle biopsies were obtained from the vastus lateralis to determine size and contractile properties of isolated slow [myosin heavy chain (MHC) I] and fast (MHC IIa) myofibers, MHC composition, and muscle protein concentration. Aerobic capacity was higher (P < 0.05) after training in both YM (16 ± 2%) and OM (13 ± 3%). Quadriceps muscle volume, determined via MRI, was 5 ± 1 and 6 ± 1% greater (P < 0.05) after training for YM and OM, respectively, which was associated with an increase in MHC I myofiber cross-sectional area (CSA), independent of age. MHC I peak power was higher (P < 0.05) after training for both YM and OM, while MHC IIa peak power was increased (P < 0.05) with training in OM only. MHC I and MHC IIa myofiber peak and normalized (peak force/CSA) force were preserved with training in OM, while MHC I peak force/CSA and MHC IIa peak force were lower (P < 0.05) after training in YM. The age-dependent adaptations in myofiber function were not due to changes in protein content, as total muscle protein and myofibrillar protein concentration were unchanged (P > 0.05) with training. Training reduced (P < 0.05) the proportion of MHC IIx isoform, independent of age, whereas no other changes in MHC composition were observed. These data suggest relative improvements in muscle size and aerobic capacity are similar between YM and OM, while adaptations in myofiber contractile function showed a general improvement in OM. Training-related increases in MHC I and MHC IIa peak power reveal that skeletal muscle of OM is responsive to aerobic exercise training and further support the use of aerobic exercise for improving cardiovascular and skeletal muscle health in older individuals. PMID:22984247

  7. Acute inhalation toxicity of carbonyl sulfide

    SciTech Connect

    Benson, J.M.; Hahn, F.F.; Barr, E.B.

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  8. Mitochondrial and nuclear DNA-repair capacity of various brain regions in mouse is altered in an age-dependent manner.

    PubMed

    Imam, Syed Z; Karahalil, Bensu; Hogue, Barbara A; Souza-Pinto, Nadja C; Bohr, Vilhelm A

    2006-08-01

    Aging is associated with increased susceptibility to neuronal loss and disruption of cerebral function either as a component of senescence, or as a consequence of neurodegenerative disease or stroke. Here we report differential changes in the repair of oxidative DNA damage in various brain regions during aging. We evaluated mitochondrial and nuclear incision activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase (UDG) and the endonuclease III homologue (NTH1) in the caudate nucleus (CN), frontal cortex (FC), hippocampus (Hip), cerebellum (CE) and brain stem (BS) of 6- and 18-month-old male C57Bl/6 mice. We observed a significant age-dependent decrease in incision activities of all three glycosylases in the mitochondria of all brain regions, whereas variable patterns of changes were seen in nuclei. No age- or region-specific changes were observed in the mitochondrial repair synthesis incorporation of uracil-initiated base-excision repair (BER). We did not observe any age or region dependent differences in levels of BER proteins among the five brain regions. In summary, our data suggest that a decreased efficiency of mitochondrial BER-glycosylases and increased oxidative damage to mitochondrial DNA might contribute to the normal aging process. These data provide a novel characterization of oxidative DNA damage processing in different brain regions implicated in various neurodegenerative disorders, and suggest that this process is regulated in an age-dependent manner. Manipulation of DNA repair mechanisms may provide a strategy to prevent neuronal loss during age-dependent neurodegenerative disorders. PMID:16005114

  9. Fructose and glucose differentially affect aging and carbonyl/oxidative stress parameters in Saccharomyces cerevisiae cells.

    PubMed

    Semchyshyn, Halyna M; Lozinska, Liudmyla M; Miedzobrodzki, Jacek; Lushchak, Volodymyr I

    2011-05-15

    Fructose is commonly used as an industrial sweetener and has been excessively consumed in human diets in the last decades. High fructose intake is causative in the development of metabolic disorders, but the mechanisms underlying fructose-induced disturbances are under debate. Fructose compared to glucose has been found to be a more potent initiator of the glycation reaction. Therefore, we supposed that glucose and fructose might have different vital effects. Here we compare the effects of glucose and fructose on yeast cell viability and markers of carbonyl/oxidative stress. Analysis of the parameters in cells growing on glucose and fructose clearly reveals that yeast growing on fructose has higher levels of carbonyl groups in proteins, α-dicarbonyl compounds and reactive oxygen species. This may explain the observation that fructose-supplemented growth as compared with growth on glucose resulted in more pronounced age-related decline in yeast reproductive ability and higher cell mortality. The results are discussed from the point of view that fructose rather than glucose is more extensively involved in glycation and ROS generation in vivo, yeast aging and development of carbonyl/oxidative stress. It should be noted that carbohydrate restriction used in this study does not reveal a significant difference between markers of aging and carbonyl/oxidative stress in yeasts cultivated on glucose and fructose.

  10. Age-dependent homeostatic plasticity of GABAergic signaling in developing retinal networks.

    PubMed

    Hennig, Matthias H; Grady, John; van Coppenhagen, James; Sernagor, Evelyne

    2011-08-24

    Developing retinal ganglion cells fire in correlated spontaneous bursts, resulting in propagating waves with robust spatiotemporal features preserved across development and species. Here we investigate the effects of homeostatic adaptation on the circuits controlling retinal waves. Mouse retinal waves were recorded in vitro for up to 35 h with a multielectrode array in presence of the GABA(A) antagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4-P6, when GABA(A) signaling is depolarizing in ganglion cells, and at P7-P10, when GABA(A) signaling is hyperpolarizing. At all ages, bicuculline initially increased the wave sizes and other activity metrics. At P5-P6, wave sizes decreased toward control levels within a few hours while firing remained strong, but this ability to compensate disappeared entirely from P7 onwards. This demonstrates that homeostatic control of spontaneous retinal activity maintains specific network dynamic properties in an age-dependent manner, and suggests that the underlying mechanism is linked to GABA(A) signaling. PMID:21865458

  11. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens

    PubMed Central

    Sheil, Conor J.; Goncharov, Alexander V.

    2016-01-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  12. Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle.

    PubMed

    Gao, Zhen; Kelly, Michael C; Yu, Dehong; Wu, Hao; Lin, Xi; Chi, Fang-lu; Chen, Ping

    2016-04-01

    Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies.

  13. Age-Dependent Susceptibility to Enteropathogenic Escherichia coli (EPEC) Infection in Mice

    PubMed Central

    Dupont, Aline; Sommer, Felix; Zhang, Kaiyi; Repnik, Urska; Basic, Marijana; Bleich, André; Kühnel, Mark; Bäckhed, Fredrik; Litvak, Yael; Fulde, Marcus; Rosenshine, Ilan; Hornef, Mathias W.

    2016-01-01

    Enteropathogenic Escherichia coli (EPEC) represents a major causative agent of infant diarrhea associated with significant morbidity and mortality in developing countries. Although studied extensively in vitro, the investigation of the host-pathogen interaction in vivo has been hampered by the lack of a suitable small animal model. Using RT-PCR and global transcriptome analysis, high throughput 16S rDNA sequencing as well as immunofluorescence and electron microscopy, we characterize the EPEC-host interaction following oral challenge of newborn mice. Spontaneous colonization of the small intestine and colon of neonate mice that lasted until weaning was observed. Intimate attachment to the epithelial plasma membrane and microcolony formation were visualized only in the presence of a functional bundle forming pili (BFP) and type III secretion system (T3SS). Similarly, a T3SS-dependent EPEC-induced innate immune response, mediated via MyD88, TLR5 and TLR9 led to the induction of a distinct set of genes in infected intestinal epithelial cells. Infection-induced alterations of the microbiota composition remained restricted to the postnatal period. Although EPEC colonized the adult intestine in the absence of a competing microbiota, no microcolonies were observed at the small intestinal epithelium. Here, we introduce the first suitable mouse infection model and describe an age-dependent, virulence factor-dependent attachment of EPEC to enterocytes in vivo. PMID:27159323

  14. Microscale Mechanism of Age Dependent Wetting Properties of Prickly Pear Cacti (Opuntia).

    PubMed

    Rykaczewski, Konrad; Jordan, Jacob S; Linder, Rubin; Woods, Erik T; Sun, Xiaoda; Kemme, Nicholas; Manning, Kenneth C; Cherry, Brian R; Yarger, Jeffery L; Majure, Lucas C

    2016-09-13

    Cacti thrive in xeric environments through specialized water storage and collection tactics such as a shallow, widespread root system that maximizes rainwater absorption and spines adapted for fog droplet collection. However, in many cacti, the epidermis, not the spines, dominates the exterior surface area. Yet, little attention has been dedicated to studying interactions of the cactus epidermis with water drops. Surprisingly, the epidermis of plants in the genus Opuntia, also known as prickly pear cacti, has water-repelling characteristics. In this work, we report that surface properties of cladodes of 25 taxa of Opuntia grown in an arid Sonoran climate switch from water-repelling to superwetting under water impact over the span of a single season. We show that the old cladode surfaces are not superhydrophilic, but have nearly vanishing receding contact angle. We study water drop interactions with, as well as nano/microscale topology and chemistry of, the new and old cladodes of two Opuntia species and use this information to uncover the microscopic mechanism underlying this phenomenon. We demonstrate that composition of extracted wax and its contact angle do not change significantly with time. Instead, we show that the reported age dependent wetting behavior primarily stems from pinning of the receding contact line along multilayer surface microcracks in the epicuticular wax that expose the underlying highly hydrophilic layers.

  15. Microscale Mechanism of Age Dependent Wetting Properties of Prickly Pear Cacti (Opuntia).

    PubMed

    Rykaczewski, Konrad; Jordan, Jacob S; Linder, Rubin; Woods, Erik T; Sun, Xiaoda; Kemme, Nicholas; Manning, Kenneth C; Cherry, Brian R; Yarger, Jeffery L; Majure, Lucas C

    2016-09-13

    Cacti thrive in xeric environments through specialized water storage and collection tactics such as a shallow, widespread root system that maximizes rainwater absorption and spines adapted for fog droplet collection. However, in many cacti, the epidermis, not the spines, dominates the exterior surface area. Yet, little attention has been dedicated to studying interactions of the cactus epidermis with water drops. Surprisingly, the epidermis of plants in the genus Opuntia, also known as prickly pear cacti, has water-repelling characteristics. In this work, we report that surface properties of cladodes of 25 taxa of Opuntia grown in an arid Sonoran climate switch from water-repelling to superwetting under water impact over the span of a single season. We show that the old cladode surfaces are not superhydrophilic, but have nearly vanishing receding contact angle. We study water drop interactions with, as well as nano/microscale topology and chemistry of, the new and old cladodes of two Opuntia species and use this information to uncover the microscopic mechanism underlying this phenomenon. We demonstrate that composition of extracted wax and its contact angle do not change significantly with time. Instead, we show that the reported age dependent wetting behavior primarily stems from pinning of the receding contact line along multilayer surface microcracks in the epicuticular wax that expose the underlying highly hydrophilic layers. PMID:27537082

  16. Consideration of age-dependent radium retention in people on the basis of the beagle model

    SciTech Connect

    Parks, N.J.; Keane, A.T.

    1981-01-01

    This paper examines in humans the proposition emanating from studies in beagles that long-term retention of radium varies in proportion to the calcium addition rate at the time of intake. Because data on the calcium addition rate in younger humans were fragmentary, human calcium-addition rates were scaled from those in beagles, the relative calcium accretion rates in the two species at equivalent stages of skeletal growth providing the scaling factor. The variation of radium retention with age was determined by fitting a modified power function to data on the retention of radium from about 30 to 15,000 days following a series of therapeutic injections of /sup 226/Ra in humans ranging in age from 18 to 63 yr. The fractional retention R at t days following a single injection of /sup 226/Ra was described by R = (1 + t/d)/sup -0/ /sup 44/. The age-dependent time constant d in the retention function was found to be proportional to the calcium addition rate at the time of injection in subjects receiving < 200 ..mu..g /sup 226/Ra.

  17. Metallothionein modulation in relation to cadmium bioaccumulation and age-dependent sensitivity of Chironomus riparius larvae.

    PubMed

    Toušová, Zuzana; Kuta, Jan; Hynek, David; Adam, Vojtěch; Kizek, René; Bláha, Luděk; Hilscherová, Klára

    2016-06-01

    The goal of this study was to contribute to understanding of the mechanisms behind sensitivity differences between early and late instar larvae of Chironomus riparius and to address the influence of the differences in standard testing approaches on the toxicity evaluation. A 10-day contact sediment toxicity test was carried out to assess sensitivity to cadmium exposure in relation to different age and laboratory culture line origin of test organisms. Chironomid larvae of early (OECD 218 method) and late instar (US-EPA600/R-99/064 method) differed substantially in sensitivity of traditional endpoints (OECD: LOEC 50 and 10 μg Cd/g dry weight (dw); US-EPA: LOEC > 1000 and 100 μg Cd/g dw for survival and growth, respectively). Bioaccumulated cadmium and metallothioneins (MTs) concentrations were analyzed to investigate the role of MTs in reduced sensitivity to cadmium in late instar larvae. Metallothioneins were induced after treatment to greater Cd concentrations, but their levels in relation to cadmium body burdens did not fully explain low sensitivity of late instars to cadmium, which indicates some other effective way of detoxification in late instars. This study brings new information related to the role of MTs in age-dependent toxicant sensitivity and discusses the implications of divergence in data generated by chironomid sediment toxicity tests by standardized methods using different instars. PMID:26957427

  18. Age-dependent stochastic models for understanding population fluctuations in continuously cultured cells

    PubMed Central

    Stukalin, Evgeny B.; Aifuwa, Ivie; Kim, Jin Seob; Wirtz, Denis; Sun, Sean X.

    2013-01-01

    For symmetrically dividing cells, large variations in the cell cycle time are typical, even among clonal cells. The consequence of this variation is important in stem cell differentiation, tissue and organ size control, and cancer development, where cell division rates ultimately determine the cell population. We explore the connection between cell cycle time variation and population-level fluctuations using simple stochastic models. We find that standard population models with constant division and death rates fail to predict the level of population fluctuation. Instead, variations in the cell division time contribute to population fluctuations. An age-dependent birth and death model allows us to compute the mean squared fluctuation or the population dispersion as a function of time. This dispersion grows exponentially with time, but scales with the population. We also find a relationship between the dispersion and the cell cycle time distribution for synchronized cell populations. The model can easily be generalized to study populations involving cell differentiation and competitive growth situations. PMID:23760298

  19. Intrinsic TGF-β signaling promotes age-dependent CD8+ T cell polyfunctionality attrition

    PubMed Central

    Bhadra, Rajarshi; Moretto, Magali M.; Castillo, Julio C.; Petrovas, Constantinos; Ferrando-Martinez, Sara; Shokal, Upasana; Leal, Manuel; Koup, Richard A.; Eleftherianos, Ioannis; Khan, Imtiaz A.

    2014-01-01

    Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8+ T cell polyfunctionality, primarily due to CD8+ T cell–extrinsic deficits, and that reduced CD8+ T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8+ T cell survival and polyfunctionality were suppressed by highly elevated TGF-β1. Furthermore, TGF-β depletion reduced effector CD8+ T cell apoptosis in both young and aged mice and enhanced effector CD8+ T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-β signaling in CD8+ T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-β1 promote apoptosis of CD8+ effector T cells and high TGF-β1 levels associated with age result in both CD8+ T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-β levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-β represents an evolutionarily conserved negative regulator of the immune response in aging organisms. PMID:24762437

  20. Reproductive and socioeconomic determinants of child survival: confounded, interactive, and age-dependent effects.

    PubMed

    Kost, K; Amin, S

    1992-01-01

    Studies of infant and child mortality have evolved to distinguish between two sets of explanatory variables-factors related to reproductive or maternal characteristics and socioeconomic factors, generally described as characteristics of the family or household. Almost all multivariate analyses include variables from each of these two sets, but there has been little consideration of the relationship between them. We examine how these two sets of variables jointly affect mortality. We test first for confounded effects by examining socioeconomic effects while excluding and then including reproductive variables in nested multivariate models. Next, we look for age-dependent effects among the explanatory variables and find that reproductive and socioeconomic factors affect mortality at differing ages of children. Finally, we examine interactive effects of the two sets of variables. We conclude that the higher mortality observed among the low status groups is not a result of greater concentration of poor reproductive patterns in those groups. Instead, higher status groups probably have more resources available for combating the negative effects of the same high-risk reproductive patterns. PMID:1514117

  1. Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes.

    PubMed Central

    Fülöp, T; Fóris, G; Wórum, I; Leövey, A

    1985-01-01

    Changes in the effector functions in polymorphonuclear leucocytes (PMNL), harvested from blood of young and aged healthy subjects of both sexes, were studied. FC gamma-receptor (Fc gamma R)-mediated incorporation of IgG coated 51Cr-HRBC significantly increased in the aged male group, while the phagocytosis of pre-opsonized fungi (Saccharomyces cerevisiae and Candida albicans) was independent of both the age and sex. However, the intracellular killing capacity of neutrophils obtained from aged male subjects significantly decreased toward 51Cr-labelled c. albicans. The antibody-dependent cellular cytotoxicity (ADCC) was also impaired with ageing in both sexes. The age-dependent decrease in the effector functions of PMNL may be explained, among others, by the fact that during yeast cell incorporation the increased cAMP level does not return to the basic level in the old group. On the other hand, the cGMP level which increased in PMNL of aged subjects does not show any progressive increase as in the young subjects, but remains unchanged. The oxidative metabolism producing free radicals being necessary for the effective intracellular killing and ADCC diminished in PMNL of aged subjects of both sexes. The above findings indicate that the adaptation of cyclic nucleotide system and the oxidative burst to the cell activation becomes impaired with ageing. PMID:2994926

  2. Age-dependent modulation of vascular niches for haematopoietic stem cells.

    PubMed

    Kusumbe, Anjali P; Ramasamy, Saravana K; Itkin, Tomer; Mäe, Maarja Andaloussi; Langen, Urs H; Betsholtz, Christer; Lapidot, Tsvee; Adams, Ralf H

    2016-04-21

    Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells. The properties of niche-forming vessels and their changes in the ageing organism remain incompletely understood. Here we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and platelet-derived growth factor receptor-β (PDGFRβ)-positive perivascular cells, arteriole formation and elevated levels of cellular stem cell factor. Although endothelial hypoxia-inducible factor signalling promotes some of these changes, it fails to enhance vascular niche function because of a lack of arterialization and expansion of PDGFRβ-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings indicate that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes.

  3. Age-dependent changes in microscale stiffness and mechanoresponses of cells.

    PubMed

    Zahn, Jasmin T; Louban, Ilia; Jungbauer, Simon; Bissinger, Martin; Kaufmann, Dieter; Kemkemer, Ralf; Spatz, Joachim P

    2011-05-23

    Cellular ageing can lead to altered cell mechanical properties and is known to affect many fundamental physiological cell functions. To reveal age-dependent changes in cell mechanical properties and in active mechanoresponses, the stiffness of human fibroblasts from differently aged donors was determined, as well as the cell's reaction to periodic mechanical deformation of the culture substrate, and the two parameters were correlated. A comparison of the average Young's moduli revealed that cells from young donors (<25 years) are considerably stiffer than cells from older donors (>30 years). The reduced stiffness of cells from the older donor group corresponds to the measured decrease of actin in these cells. Remarkably, cells from the older donor group show a significantly faster reorganization response to periodic uniaxial tensile strain than cells from the young donor group. The impact of a reduced amount of actin on cell stiffness and cell reorganization kinetics is further confirmed by experiments where the amount of cellular actin in cells from the young donor group was decreased by transient siRNA knockdown of the actin gene. These cells show a reduced stiffness and enhanced reorganization speed, and in this way mimic the properties and behavior of cells from the older donor group. These results demonstrate that mechanical properties of human fibroblasts depend on the donor's age, which in turn may affect the cells' active responses to mechanical stimulations.

  4. In vitro age dependent response of macrophages to micro and nano titanium dioxide particles.

    PubMed

    Bruno, Marcos E; Sittner, Maximiliano; Cabrini, Rómulo L; Guglielmotti, María B; Olmedo, Daniel G; Tasat, Deborah R

    2015-02-01

    As a result of corrosion, microparticles (MP) and/or nanoparticles (NP) can be released from the metallic implants surface into the bioenvironment. The biological response to these particles depends not only on the physico-chemical properties of the particles but also on host factors, such as age. Macrophages have attracted wide concern in biomedicine. The aim of this investigation was to study the age related biological response of macrophages to TiO2 -MP and NP in vitro. Alveolar macrophages (AM) obtained from young and senescent rats were cultured and exposed to TiO2 -MP and NP. Cell metabolism, superoxide anion (O2 (-) ) and nitric oxide (NO) generation, and cytokine release (IL-6, TNFα, IL-10) were measured. Cell metabolism was not affected by particle exposure. O2 (-) and NO generation increased in a dose dependent manner. A marked increase on IL-6 release was found in the young-AM subpopulation exposed to TiO2 -MP. Conversely, both particle sizes induced a dose dependent release of TNFα in senescent-AM. Only the highest concentration of TiO2 -particles caused a significant increase in IL-10 release in AM-cultures. These observations lend strong support to the suggestion that cellular response of macrophages to TiO2 -particles is age dependent. The biological effect of the particles would seem to be more deleterious in the senescent age-group.

  5. Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity.

    PubMed

    Kinyua, Ann W; Yang, Dong Joo; Chang, Inik; Kim, Ki Woo

    2016-01-01

    The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. PMID:27598259

  6. Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity

    PubMed Central

    Kinyua, Ann W.; Yang, Dong Joo; Chang, Inik; Kim, Ki Woo

    2016-01-01

    The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. PMID:27598259

  7. Age-dependent decline in dental pulp regeneration after pulpectomy in dogs.

    PubMed

    Iohara, Koichiro; Murakami, Masashi; Nakata, Kazuhiko; Nakashima, Misako

    2014-04-01

    The age-associated decline in the regenerative abilities of mesenchymal stem cells (MSCs) may be due to age-related changes in reduction in number, intrinsic properties of MSCs and extrinsic factors of the extracellular environment (the stem cell niche). The effect of age on the efficacy of MSC transplantation on regeneration, however, has not been clearly demonstrated due to variable methods of isolation of MSCs and variations in stem cell populations. In this study, dental pulp stem cell (DPSC) subsets were isolated from young and aged dog teeth based on their migratory response to granulocyte-colony stimulating factor (G-CSF) (MDPSCs). In order to study the age-associated changes, their biological properties and stability were compared and the regenerative potential was examined in a pulpectomized tooth model in aged dogs. MDPSCs from aged dogs were efficiently enriched in stem cells, expressing trophic factors with high proliferation, migration and anti-apoptotic effects as in MDPSCs from young dogs. However, pulp regeneration was retarded 120 days after autologous transplantation of aged MDPSCs. We further demonstrated that isolated periodontal ligament stem cells (PDLSCs) from aged dogs, representative of migrating stem cells from outside of the tooth compartment to regenerate pulp tissue, had lower proliferation, migration and anti-apoptotic abilities. These results therefore provide a better understanding of the mechanisms involved in the age-dependent decline in pulp regeneration, which are attributed to a decrease in the regenerative potential of resident stem cells.

  8. Accommodating volume-constant age-dependent optical (AVOCADO) model of the crystalline GRIN lens.

    PubMed

    Sheil, Conor J; Goncharov, Alexander V

    2016-05-01

    The purpose of this manuscript is to introduce a new age-dependent model of the human lens with two GRIN power distributions (axial and radial) that allow decoupling of its refractive power and axial optical path length. The aspect ratio of the lens core can be held constant under accommodation, as well as the lens volume by varying the asphericity of the lens external surfaces. The spherical aberration calculated by exact raytracing is shown to be in line with experimental data. The proposed model is compared to previous GRIN models from the literature, and it is concluded that the features of the new model will be useful for GRIN reconstruction in future experimental studies; in particular, studies of the accommodation-dependent properties of the ageing human eye. A proposed logarithmic model of the lens core enables decoupling of three fundamental optical characteristics of the lens, namely axial optical path length, optical power and third-order spherical aberration, without changing the external shape of the lens. Conversely, the near-surface GRIN structure conforms to the external shape of the lens, which is necessary for accommodation modelling. PMID:27231637

  9. Large-scale age-dependent skewed sex ratio in a sexually dimorphic avian scavenger.

    PubMed

    Lambertucci, Sergio A; Carrete, Martina; Donázar, José Antonio; Hiraldo, Fernando

    2012-01-01

    Age-dependent skewed sex ratios have been observed in bird populations, with adult males generally outnumbering females. This trend is mainly driven by higher female mortality, sometimes associated with anthropogenic factors. Despite the large amount of work on bird sex ratios, research examining the spatial stability of adult sex ratios is extremely scarce. The Andean condor (Vultur gryphus) is the only bird of prey with strong sexual dimorphism favouring males (males are 30% heavier than females). By examining data from most of its South-American range, we show that while the juvenile sex ratio is balanced, or even female-skewed, the sex ratio becomes increasing male-skewed with age, with adult males outnumbering females by >20%, and, in some cases by four times more. This result is consistent across regions and independent of the nature of field data. Reasons for this are unknown but it can be hypothesized that the progressive disappearance of females may be associated with mortality caused by anthropogenic factors. This idea is supported by the asymmetric habitat use by the two sexes, with females scavenging in more humanized areas. Whatever the cause, male-skewed adult sex ratios imply that populations of this endangered scavenger face higher risks of extinction than previously believed.

  10. Large-Scale Age-Dependent Skewed Sex Ratio in a Sexually Dimorphic Avian Scavenger

    PubMed Central

    Lambertucci, Sergio A.; Carrete, Martina; Donázar, José Antonio; Hiraldo, Fernando

    2012-01-01

    Age-dependent skewed sex ratios have been observed in bird populations, with adult males generally outnumbering females. This trend is mainly driven by higher female mortality, sometimes associated with anthropogenic factors. Despite the large amount of work on bird sex ratios, research examining the spatial stability of adult sex ratios is extremely scarce. The Andean condor (Vultur gryphus) is the only bird of prey with strong sexual dimorphism favouring males (males are 30% heavier than females). By examining data from most of its South-American range, we show that while the juvenile sex ratio is balanced, or even female-skewed, the sex ratio becomes increasing male-skewed with age, with adult males outnumbering females by >20%, and, in some cases by four times more. This result is consistent across regions and independent of the nature of field data. Reasons for this are unknown but it can be hypothesized that the progressive disappearance of females may be associated with mortality caused by anthropogenic factors. This idea is supported by the asymmetric habitat use by the two sexes, with females scavenging in more humanized areas. Whatever the cause, male-skewed adult sex ratios imply that populations of this endangered scavenger face higher risks of extinction than previously believed. PMID:23029488

  11. Age-dependent relevance of endogenous 5-lipoxygenase derivatives in anxiety-like behavior in mice.

    PubMed

    Leo, Luciana M; Almeida-Corrêa, Suellen; Canetti, Claudio A; Amaral, Olavo B; Bozza, Fernando A; Pamplona, Fabricio A

    2014-01-01

    When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocannabinoid system. Although 5-LO inhibition by MK-886 reduced lipoxin A4 levels in the brain, no effect was found in the elevated plus maze (EPM), even at the highest possible doses, via i.p. (10 mg/kg,) or i.c.v. (500 pmol/2 µl) routes. Accordingly, no alterations in anxiety-like behavior in the EPM test were observed in 5-LO KO mice. Interestingly, aged mice, which show reduced circulating lipoxin A4 levels, were sensitive to MK-886, displaying an anxiogenic-like state in response to treatment. Moreover, exogenous lipoxin A4 induced an anxiolytic-like profile in the EPM test. Our findings are in line with other reports showing no difference between FLAP KO or 5-LO KO and their control strains in adult mice, but increased anxiety-like behavior in aged mice. We also show for the first time that lipoxin A4 affects mouse behavior. In conclusion, we propose an age-dependent relevancy of endogenous 5-LO derivatives in the modulation of anxiety-like behavior, in addition to a potential for exogenous lipoxin A4 in producing an anxiolytic-like state.

  12. Adenomatous polyposis coli heterozygous knockout mice display hypoactivity and age-dependent working memory deficits

    PubMed Central

    Koshimizu, Hisatsugu; Fukui, Yasuyuki; Takao, Keizo; Ohira, Koji; Tanda, Koichi; Nakanishi, Kazuo; Toyama, Keiko; Oshima, Masanobu; Taketo, Makoto Mark; Miyakawa, Tsuyoshi

    2011-01-01

    A tumor suppressor gene, Adenomatous polyposis coli (Apc), is expressed in the nervous system from embryonic to adulthood stages, and transmits the Wnt signaling pathway in which schizophrenia susceptibility genes, including T-cell factor 4 (TCF4) and calcineurin (CN), are involved. However, the functions of Apc in the nervous system are largely unknown. In this study, as the first evaluation of Apc function in the nervous system, we have investigated the behavioral significance of the Apc gene, applying a battery of behavioral tests to Apc heterozygous knockout (Apc+/−) mice. Apc+/− mice showed no significant impairment in neurological reflexes or sensory and motor abilities. In various tests, including light/dark transition, open-field, social interaction, eight-arm radial maze, and fear conditioning tests, Apc+/− mice exhibited hypoactivity. In the eight-arm radial maze, Apc+/− mice 6–7 weeks of age displayed almost normal performance, whereas those 11–12 weeks of age showed a severe performance deficit in working memory, suggesting that Apc is involved in working memory performance in an age-dependent manner. The possibility that anemia, which Apc+/− mice develop by 17 weeks of age, impairs working memory performance, however, cannot be excluded. Our results suggest that Apc plays a role in the regulation of locomotor activity and presumably working memory performance. PMID:22347851

  13. Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus

    PubMed Central

    Arslan, Fatma Demet; Serdar, Muhittin; Merve Ari, Elif; Onur Oztan, Mustafa; Hikmet Kozcu, Sureyya; Tarhan, Huseyin; Cakmak, Ozgur; Zeytinli, Merve; Yasar Ellidag, Hamit

    2016-01-01

    Background In order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges. Objectives The purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. Materials and Methods A total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated. Results No statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established. Conclusions These results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges. PMID:27617078

  14. Prevalence and age-dependent occurrence of intestinal protozoan infections in suckling piglets.

    PubMed

    Damriyasa, I Made; Bauer, Christian

    2006-01-01

    A cross-sectional survey was performed on 20 pig breeding farms in southern Hesse, central Germany, to evaluate the prevalence and age-dependent occurrence of intestinal protozoan parasites in unweaned piglets. Faecal samples of 514 clinically unaffected piglets of different age (< 1 to 5-7 weeks) were examined using the sodium acetate-acetic acid-formalin (SAF) concentration technique. Infections with the following protozoan species were detected: Balantidium coli (16 of 20 farms), Entamoeba sp. (15), Jodamoeba sp. (14), Isospora (I.) suis (9), Chilomastix sp. (6) and Eimeria spp. (6). The protozoan species differed in the start and course of (oo)cyst excretion. I. suis oocysts and Jodamoeba cysts were detected already in the first week of life whereas shedding of the other parasites started later on. The prevalence of Isospora oocyst excretion increased to a maximum (18%) in 2-3 weeks old animals followed by a sharp decline. The proportion of Balantidium, Entamoeba or Jodamoeba positive suckling piglets continously increased until the age of 5-7 weeks to 60%, 52% and 22%, respectively, whereas that of Chilomastix positive animals remained on a low level of 8-12% independent of the age. Eimeria oocysts were found transiently in the faeces of 1-4 weeks old piglets. PMID:17009710

  15. Assessment of age-dependent uranium intake due to drinking water in Hyderabad, India.

    PubMed

    Balbudhe, A Y; Srivastava, S K; Vishwaprasad, K; Srivastava, G K; Tripathi, R M; Puranik, V D

    2012-03-01

    A study has been done to assess the uranium intake through drinking water. The area of study is twin cities of Hyderabad and Secunderabad, India. Uranium concentration in water samples was analysed by laser-induced fluorimetry. The associated age-dependent uranium intake was estimated by taking the prescribed water intake values. The concentration of uranium varies from below detectable level (minimum detectable level = 0.20 ± 0.02 μg l(-1)) to 2.50 ± 0.18 μg l(-1), with the geometric mean (GM) of 0.67 μg l(-1) in tap water, whereas in ground water, the range is 0.60 ± 0.05 to 82 ± 7.1 µg l(-1) with GM of 10.07 µg l(-1). The daily intake of uranium by drinking water pathway through tap water for various age groups is found to vary from 0.14 to 9.50 µg d(-1) with mean of 1.55 µg d(-1).

  16. Large-scale age-dependent skewed sex ratio in a sexually dimorphic avian scavenger.

    PubMed

    Lambertucci, Sergio A; Carrete, Martina; Donázar, José Antonio; Hiraldo, Fernando

    2012-01-01

    Age-dependent skewed sex ratios have been observed in bird populations, with adult males generally outnumbering females. This trend is mainly driven by higher female mortality, sometimes associated with anthropogenic factors. Despite the large amount of work on bird sex ratios, research examining the spatial stability of adult sex ratios is extremely scarce. The Andean condor (Vultur gryphus) is the only bird of prey with strong sexual dimorphism favouring males (males are 30% heavier than females). By examining data from most of its South-American range, we show that while the juvenile sex ratio is balanced, or even female-skewed, the sex ratio becomes increasing male-skewed with age, with adult males outnumbering females by >20%, and, in some cases by four times more. This result is consistent across regions and independent of the nature of field data. Reasons for this are unknown but it can be hypothesized that the progressive disappearance of females may be associated with mortality caused by anthropogenic factors. This idea is supported by the asymmetric habitat use by the two sexes, with females scavenging in more humanized areas. Whatever the cause, male-skewed adult sex ratios imply that populations of this endangered scavenger face higher risks of extinction than previously believed. PMID:23029488

  17. Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells.

    PubMed

    Velarde, Michael C; Demaria, Marco; Melov, Simon; Campisi, Judith

    2015-08-18

    Tissue homeostasis declines with age partly because stem/progenitor cells fail to self-renew or differentiate. Because mitochondrial damage can accelerate aging, we tested the hypothesis that mitochondrial dysfunction impairs stem cell renewal or function. We developed a mouse model, Tg(KRT14-cre/Esr1) (20Efu/J) × Sod2 (tm1Smel) , that generates mitochondrial oxidative stress in keratin 14-expressing epidermal stem/progenitor cells in a temporally controlled manner owing to deletion of Sod2, a nuclear gene that encodes the mitochondrial antioxidant enzyme superoxide dismutase 2 (Sod2). Epidermal Sod2 loss induced cellular senescence, which irreversibly arrested proliferation in a fraction of keratinocytes. Surprisingly, in young mice, Sod2 deficiency accelerated wound closure, increasing epidermal differentiation and reepithelialization, despite the reduced proliferation. In contrast, at older ages, Sod2 deficiency delayed wound closure and reduced epidermal thickness, accompanied by epidermal stem cell exhaustion. In young mice, Sod2 deficiency accelerated epidermal thinning in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, phenocopying the reduced regeneration of older Sod2-deficient skin. Our results show a surprising beneficial effect of mitochondrial dysfunction at young ages, provide a potential mechanism for the decline in epidermal regeneration at older ages, and identify a previously unidentified age-dependent role for mitochondria in skin quality and wound closure.

  18. Pilocarpine Seizures Cause Age-Dependent Impairment in Auditory Location Discrimination

    PubMed Central

    Neill, John C; Liu, Zhao; Mikati, Mohammad; Holmes, Gregory L

    2005-01-01

    Children who have status epilepticus have continuous or rapidly repeating seizures that may be life-threatening and may cause life-long changes in brain and behavior. The extent to which status epilepticus causes deficits in auditory discrimination is unknown. A naturalistic auditory location discrimination method was used to evaluate this question using an animal model of status epilepticus. Male Sprague-Dawley rats were injected with saline on postnatal day (P) 20, or a convulsant dose of pilocarpine on P20 or P45. Pilocarpine on either day induced status epilepticus; status epilepticus at P45 resulted in CA3 cell loss and spontaneous seizures, whereas P20 rats had no cell loss or spontaneous seizures. Mature rats were trained with sound-source location and sound-silence discriminations. Control (saline P20) rats acquired both discriminations immediately. In status epilepticus (P20) rats, acquisition of the sound-source location discrimination was moderately impaired. Status epilepticus (P45) rats failed to acquire either sound-source location or sound-silence discriminations. Status epilepticus in rat causes an age-dependent, long-term impairment in auditory discrimination. This impairment may explain one cause of impaired auditory location discrimination in humans. PMID:16596970

  19. Effect of hydrogen atoms on the structures of trinuclear metal carbonyl clusters: trinuclear manganese carbonyl hydrides.

    PubMed

    Liu, Xian-mei; Wang, Chao-yang; Li, Qian-shu; Xie, Yaoming; King, R Bruce; Schaefer, Henry F

    2009-05-18

    The structures of the trinuclear manganese carbonyl hydrides H(3)Mn(3)(CO)(n) (n = 12, 11, 10, 9) have been investigated by density functional theory (DFT). Optimization of H(3)Mn(3)(CO)(12) gives the experimentally known structure in which all carbonyl groups are terminal and each edge of a central Mn(3) equilateral triangle is bridged by a single hydrogen atom. This structure establishes the canonical distance 3.11 A for the Mn-Mn single bond satisfying the 18-electron rule. The central triangular (mu-H)(3)Mn(3) unit is retained in the lowest energy structure of H(3)Mn(3)(CO)(11), which may thus be derived from the H(3)Mn(3)(CO)(12) structure by removal of a carbonyl group with concurrent conversion of one of the remaining carbonyl groups into a semibridging carbonyl group to fill the resulting hole. The potential energy surface of H(3)Mn(3)(CO)(10) is relatively complicated with six singlet and five triplet structures. One of the lower energy H(3)Mn(3)(CO)(10) structures has one of the hydrogen atoms bridging the entire Mn(3) triangle and the other two hydrogen atoms bridging Mn-Mn edges. This H(3)Mn(3)(CO)(10) structure achieves the favored 18-electron configuration with a very short MnMn triple bond of 2.36 A. The other low energy H(3)Mn(3)(CO)(10) structure retains the (mu-H)(3)Mn(3) core of H(3)Mn(3)(CO)(12) but has a unique six-electron donor eta(2)-mu(3) carbonyl group bridging the entire Mn(3) triangle similar to the unique carbonyl group in the known compound Cp(3)Nb(3)(CO)(6)(eta(2)-mu(3)-CO). For H(3)Mn(3)(CO)(9) a structure with a central (mu(3)-H)(2)Mn(3) trigonal bipyramid lies >20 kcal/mol below any of the other structures. Triplet structures were found for the unsaturated H(3)Mn(3)(CO)(n) (n = 11, 10, 9) systems but at significantly higher energies than the lowest lying singlet structures.

  20. Human TTR conformation altered by rhenium tris-carbonyl derivatives.

    PubMed

    Ciccone, Lidia; Policar, Clotilde; Stura, Enrico A; Shepard, William

    2016-09-01

    Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu(82), may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69Å, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. PMID:27402536

  1. Gas-phase chemistry of ruthenium and rhodium carbonyl complexes.

    PubMed

    Cao, Shiwei; Wang, Yang; Qin, Zhi; Fan, Fangli; Haba, Hiromitsu; Komori, Yukiko; Wu, Xiaolei; Tan, Cunmin; Zhang, Xin

    2016-01-01

    Short-lived ruthenium and rhodium isotopes were produced from a (252)Cf spontaneous fission (SF) source. Their volatile carbonyl complexes were formed in gas-phase reactions in situ with the carbon-monoxide containing gas. A gas-jet system was employed to transport the volatile carbonyls from the recoil chamber to the chemical separation apparatus. The gas-phase chemical behaviors of these carbonyl complexes were studied using an online low temperature isothermal chromatography (IC) technique. Long IC columns made up of FEP Teflon were used to obtain the chemical information of the high-volatile Ru and Rh carbonyls. By excluding the influence of precursor effects, short-lived isotopes of (109-110)Ru and (111-112)Rh were used to represent the chemical behaviours of Ru and Rh carbonyls. Relative chemical yields of about 75% and 20% were measured for Ru(CO)5 and Rh(CO)4, respectively, relative to the yields of KCl aerosols transported in Ar gas. The adsorption enthalpies of ruthenium and rhodium carbonyl complexes on a Teflon surface were determined to be around ΔHads = -33(+1)(-2) kJ mol(-1) and -36(+2)(-1) kJ mol(-1), respectively, by fitting the breakthrough curves of the corresponding carbonyl complexes with a Monte Carlo simulation program. Different from Mo and Tc carbonyls, a small amount of oxygen gas was found to be not effective for the chemical yields of ruthenium and rhodium carbonyl complexes. The general chemical behaviors of short-lived carbonyl complexes of group VI-IX elements were discussed, which can be used in the future study on the gas-phase chemistry of superheavy elements - Bh, Hs, and Mt carbonyls. PMID:26573993

  2. Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency

    PubMed Central

    Lorenzo, Damaris N.; Healy, Jane A.; Hostettler, Janell; Davis, Jonathan; Yang, Jiayu; Wang, Chao; Hohmeier, Hans Ewald; Zhang, Mingjie; Bennett, Vann

    2015-01-01

    Rare functional variants of ankyrin-B have been implicated in human disease, including hereditary cardiac arrhythmia and type 2 diabetes (T2D). Here, we developed murine models to evaluate the metabolic consequences of these alterations in vivo. Specifically, we generated knockin mice that express either the human ankyrin-B variant R1788W, which is present in 0.3% of North Americans of mixed European descent and is associated with T2D, or L1622I, which is present in 7.5% of African Americans. Young AnkbR1788W/R1788W mice displayed primary pancreatic β cell insufficiency that was characterized by reduced insulin secretion in response to muscarinic agonists, combined with increased peripheral glucose uptake and concomitantly increased plasma membrane localization of glucose transporter 4 (GLUT4) in skeletal muscle and adipocytes. In contrast, older AnkbR1788W/R1788W and AnkbL1622I/L1622I mice developed increased adiposity, a phenotype that was reproduced in cultured adipocytes, and insulin resistance. GLUT4 trafficking was altered in animals expressing mutant forms of ankyrin-B, and we propose that increased cell surface expression of GLUT4 in skeletal muscle and fatty tissue of AnkbR1788W/R1788W mice leads to the observed age-dependent adiposity. Together, our data suggest that ankyrin-B deficiency results in a metabolic syndrome that combines primary pancreatic β cell insufficiency with peripheral insulin resistance and is directly relevant to the nearly one million North Americans bearing the R1788W ankyrin-B variant. PMID:26168218

  3. Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences.

    PubMed

    Jintaridth, Pornrutsami; Mutirangura, Apiwat

    2010-04-01

    Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but also in cancer cells. Loss of LINE-1 methylation has been characterized in many cancers. Here, we evaluated the methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers between 20 and 88 yr of age. Age was negatively associated with methylation levels of Alu (r = -0.452, P < 10(-3)) and HERV-K (r = -0.326, P < 10(-3)) but not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during ages 34-68 yr, and loss of methylation of HERV-K occurred during ages 40-63 yr and again during ages 64-83 yr. Interestingly, methylation of Alu and LINE-1 are directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10(-3)). Therefore, only some types of IRSs lose methylation at certain ages. Moreover, Alu and HERV-K become hypomethylated differently. Finally, there may be several mechanisms of global methylation. However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process.

  4. Age-dependent variation of the Gradient Index profile in human crystalline lenses.

    PubMed

    de Castro, A; Siedlecki, D; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, S

    2011-01-01

    PURPOSE: To reconstruct the gradient index (GRIN) profile of human crystalline lenses ex-vivo using Optical Coherence Tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. METHODS: Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. RESULTS: The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. CONCLUSION: Optical Coherence Tomography allowed optical, non-invasive measurement of the 2-D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau. PMID:22865954

  5. Age-dependent uncoupling of mitochondria from Ca2+ release units in skeletal muscle

    PubMed Central

    Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T.; Boncompagni, Simona; Protasi, Feliciano

    2015-01-01

    Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling. Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8±0.4 vs. 5.5±0.3 tethers/100μm2) and CRU-mitochondrial pair density (37.4±0.8 vs. 27.0±0.7 pairs/100μm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68±0.08 vs 1.37±0.03) and mitochondrial Ca2+ uptake (9.6±0.050 vs 6.58±0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance. PMID:26485763

  6. Cardioprotective effects of quercetin against ischemia-reperfusion injury are age-dependent.

    PubMed

    Bartekova, M; Radosinska, J; Pancza, D; Barancik, M; Ravingerova, T

    2016-09-19

    Quercetin, a polyphenolic compound present in various types of food, has been shown to exert beneficial effects in different cardiac as well as non-cardiac ischemia/reperfusion (I/R) models in adult animals. However, there is no evidence about the effects of quercetin on I/R injury in non-mature animals, despite the fact that efficiency of some interventions against I/R is age-dependent. This study was aimed to investigate the effects of chronic quercetin treatment on I/R injury in juvenile and adult rat hearts. Juvenile (4-week-old) as well as adult (12-week-old) rats were treated with quercetin (20 mg/kg/day) for 4 weeks, hearts were excised and exposed to 25-min global ischemia followed by 40-min reperfusion. Functional parameters of hearts and occurrence of reperfusion arrhythmias were registered to assess the cardiac function. Our results have shown that quercetin improved post-ischemic recovery of LVDP, as well as recovery of markers of contraction and relaxation, +(dP/dt)max and -(dP/dt)max, respectively, in juvenile hearts, but not in adult hearts. Quercetin had no impact on incidence as well as duration of reperfusion arrhythmias in animals of both ages. We conclude that the age of rats plays an important role in heart response to quercetin treatment in the particular dose and duration of the treatment. Therefore, the age of the treated subjects should be taken into consideration when choosing the dose of quercetin and duration of its application in prevention and/or treatment of cardiovascular diseases.

  7. Age-dependent variation of the Gradient Index profile in human crystalline lenses

    PubMed Central

    de Castro, A.; Siedlecki, D.; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, S.

    2011-01-01

    Purpose To reconstruct the gradient index (GRIN) profile of human crystalline lenses ex-vivo using Optical Coherence Tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. Methods Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. Results The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. Conclusion Optical Coherence Tomography allowed optical, non-invasive measurement of the 2-D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau. PMID:22865954

  8. Age-dependent variation of the gradient index profile in human crystalline lenses

    NASA Astrophysics Data System (ADS)

    de Castro, Alberto; Siedlecki, Damian; Borja, David; Uhlhorn, Stephen; Parel, Jean-Marie; Manns, Fabrice; Marcos, Susana

    2011-11-01

    An investigation was carried out with the aim of reconstructing the gradient index (GRIN) profile of human crystalline lenses ex-vivo using optical coherence tomography (OCT) imaging with an optimization technique and to study the dependence of the GRIN profile with age. Cross-sectional images of nine isolated human crystalline lenses with ages ranging from 6 to 72 (post-mortem time 1 to 4 days) were obtained using a custom-made OCT system. Lenses were extracted from whole cadaver globes and placed in a measurement chamber filled with preservation medium (DMEM). Lenses were imaged with the anterior surface up and then flipped over and imaged again, to obtain posterior lens surface profiles both undistorted and distorted by the refraction through the anterior crystalline lens and GRIN. The GRIN distribution of the lens was described with three variables by means of power function, with variables being the nucleus and surface index, and a power coefficient that describes the decay of the refractive index from the nucleus to the surface. An optimization method was used to search for the parameters that produced the best match of the distorted posterior surface. The distorted surface was simulated with accuracy around the resolution of the OCT system (under 15 µm). The reconstructed refractive index values ranged from 1.356 to 1.388 for the surface, and from 1.396 to 1.434 for the nucleus. The power coefficient ranged between 3 and 18. The power coefficient increased significantly with age, at a rate of 0.24 per year. Optical coherence tomography allowed optical, non-invasive measurement of the 2D gradient index profile of the isolated human crystalline lens ex vivo. The age-dependent variation of the changes is consistent with previous data using magnetic resonance imaging, and the progressive formation of a refractive index plateau.

  9. Time-evolution of age-dependent mortality patterns in mathematical model of heterogeneous human population.

    PubMed

    Avraam, Demetris; Arnold-Gaille, Séverine; Jones, Dyfan; Vasiev, Bakhtier

    2014-12-01

    The widely-known Gompertz law of mortality states the exponential increase of mortality with age in human populations. Such an exponential increase is observed at the adulthood span, roughly after the reproductive period, while mortality data at young and extremely old ages deviate from it. The heterogeneity of human populations, i.e. the existence of subpopulations with different mortality dynamics, is a useful consideration that can explain age-dependent mortality patterns across the whole life-course. A simple mathematical model combining the heterogeneity of populations with an assumption that the mortality in each subpopulation grows exponentially with age has been proven to be capable of reproducing the entire mortality pattern in a human population including the observed peculiarities at early- and late-life intervals. In this work we fit this model to actual (Swedish) mortality data for consecutive periods and consequently describe the evolution of mortality dynamics in terms of the evolution of the model parameters over time. We have found that the evolution of the model parameters validates the applicability of the compensation law of mortality to each subpopulation separately. Furthermore, our study has indicated that the population structure changes so that the population tends to become more homogeneous over time. Finally, our analysis of the decrease of the overall mortality in a population over time has shown that this decrease is mainly due to a change in the population structure and to a lesser extent to a reduction of mortality in each of the subpopulations, the latter being represented by an alteration of the parameters that outline the exponential dynamics.

  10. Elevated Systolic Blood Pressure in Male GH Transgenic Mice Is Age Dependent

    PubMed Central

    Jara, Adam; Benner, Chance M.; Sim, Don; Liu, Xingbo; List, Edward O.; Householder, Lara A.; Berryman, Darlene E.

    2014-01-01

    Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3–12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems. PMID:24424040

  11. Cardioprotective effects of quercetin against ischemia-reperfusion injury are age-dependent.

    PubMed

    Bartekova, M; Radosinska, J; Pancza, D; Barancik, M; Ravingerova, T

    2016-09-19

    Quercetin, a polyphenolic compound present in various types of food, has been shown to exert beneficial effects in different cardiac as well as non-cardiac ischemia/reperfusion (I/R) models in adult animals. However, there is no evidence about the effects of quercetin on I/R injury in non-mature animals, despite the fact that efficiency of some interventions against I/R is age-dependent. This study was aimed to investigate the effects of chronic quercetin treatment on I/R injury in juvenile and adult rat hearts. Juvenile (4-week-old) as well as adult (12-week-old) rats were treated with quercetin (20 mg/kg/day) for 4 weeks, hearts were excised and exposed to 25-min global ischemia followed by 40-min reperfusion. Functional parameters of hearts and occurrence of reperfusion arrhythmias were registered to assess the cardiac function. Our results have shown that quercetin improved post-ischemic recovery of LVDP, as well as recovery of markers of contraction and relaxation, +(dP/dt)max and -(dP/dt)max, respectively, in juvenile hearts, but not in adult hearts. Quercetin had no impact on incidence as well as duration of reperfusion arrhythmias in animals of both ages. We conclude that the age of rats plays an important role in heart response to quercetin treatment in the particular dose and duration of the treatment. Therefore, the age of the treated subjects should be taken into consideration when choosing the dose of quercetin and duration of its application in prevention and/or treatment of cardiovascular diseases. PMID:27643931

  12. Elevated systolic blood pressure in male GH transgenic mice is age dependent.

    PubMed

    Jara, Adam; Benner, Chance M; Sim, Don; Liu, Xingbo; List, Edward O; Householder, Lara A; Berryman, Darlene E; Kopchick, John J

    2014-03-01

    Acromegaly is associated with an increased incidence of cardiovascular disease. Transgenic mice expressing bovine GH (bGH) gene have previously been used to examine the effects of chronic GH stimulation on cardiovascular function. Results concerning systolic blood pressure (SBP) in bGH mice are conflicting. We hypothesized that these discrepancies may be the result of the various ages of the mice used in previous studies. In the current study, SBP was assessed monthly in male bGH mice from 3-12 months of age. Factors known to alter blood pressure were assessed during this time and included: levels of brain natriuretic peptide (BNP) and glucose homeostasis markers, and renal levels of angiotensin-converting enzyme 2 and endothelial nitric oxide synthase. Beginning at 6 months of age bGH had increased SBP compared with wild-type controls, which remained elevated through 12 months of age. Despite having increased blood pressure and cardiac BNP mRNA, bGH mice had decreased circulating levels of BNP. Additionally, bGH mice had an age-dependent decline in insulin levels. For example, they were hyperinsulinemic at 3 months, but by 11 months of age were hypoinsulinemic relative to wild-type controls. This decrease in insulin was accompanied by improved glucose tolerance at 11 months. Finally, both angiotensin-converting enzyme 2 and endothelial nitric oxide synthase expression were severely depressed in kidneys of 11-month-old bGH mice. These results indicate that elevated SBP in bGH mice is dependent on age, independent of insulin resistance, and related to alterations in both the natriuretic peptide and renin-angiotensin systems. PMID:24424040

  13. Carbonyl emissions in diesel and biodiesel exhaust

    NASA Astrophysics Data System (ADS)

    Machado Corrêa, Sérgio; Arbilla, Graciela

    With the use of biodiesel in clear growth, it is important to quantify any potential emission benefits or liabilities of this fuel. Several researches are available concerning the regulated emissions of biodiesel/diesel blends, but there is a lack of information about non-regulated emissions. In a previous paper [Corrêa, S.M., Arbilla, G., 2006. Emissões de formaldeído e acetaldeído de misturas biodiesel/diesel. Periódico Tchê Química, 3, 54-68], the emissions of aromatic hydrocarbons were reported. In this work, seven carbonyl emissions (formaldehyde, acetaldehyde, acrolein, acetone, propionaldehyde, butyraldehyde, and benzaldehyde) were evaluated by a heavy-duty diesel engine fueled with pure diesel (D) and biodiesel blends (v/v) of 2% (B2), 5% (B5), 10% (B10), and 20% (B20). The tests were conducted using a six cylinder heavy-duty engine, typical of the Brazilian fleet of urban buses, in a steady-state condition under 1000, 1500, and 2000 rpm. The exhaust gases were diluted nearly 20 times and the carbonyls were sampled with SiO 2-C18 cartridges, impregnated with acid solution of 2,4-dinitrophenylhydrazine. The chemical analyses were performed by high performance liquid chromatography using UV detection. Using average values for the three modes of operation (1000, 1500, and 2000 rpm) benzaldehyde showed a reduction on the emission (-3.4% for B2, -5.3% for B5, -5.7% for B10, and -6.9% for B20) and all other carbonyls showed a significative increase: 2.6, 7.3, 17.6, and 35.5% for formaldehyde; 1.4, 2.5, 5.4, and 15.8% for acetaldehyde; 2.1, 5.4, 11.1, and 22.0% for acrolein+acetone; 0.8, 2.7, 4.6, and 10.0% for propionaldehyde; 3.3, 7.8, 16.0, and 26.0% for butyraldehyde.

  14. Synthesis of main-chain metal carbonyl organometallic macromolecules (MCMCOMs).

    PubMed

    Cao, Kai; Murshid, Nimer; Wang, Xiaosong

    2015-04-01

    Synthesis of main-chain metal carbonyl organometallic macromolecules (MCMCOMs) is difficult, mainly due to the instability of metal carbonyl complexes. Despite its challenge a number of MCMCOMs has been prepared by strategically using organometallic, organic, and polymer synthetic chemistry. Main contributions to this research field were reported by the groups of Tyler, Pannell, and Wang and are briefly summarized in this article.

  15. The Hydrolysis of Carbonyl Sulfide at Low Temperature: A Review

    PubMed Central

    Zhao, Shunzheng; Yi, Honghong; Tang, Xiaolong; Jiang, Shanxue; Gao, Fengyu; Zhang, Bowen; Zuo, Yanran; Wang, Zhixiang

    2013-01-01

    Catalytic hydrolysis technology of carbonyl sulfide (COS) at low temperature was reviewed, including the development of catalysts, reaction kinetics, and reaction mechanism of COS hydrolysis. It was indicated that the catalysts are mainly involved metal oxide and activated carbon. The active ingredients which can load on COS hydrolysis catalyst include alkali metal, alkaline earth metal, transition metal oxides, rare earth metal oxides, mixed metal oxides, and nanometal oxides. The catalytic hydrolysis of COS is a first-order reaction with respect to carbonyl sulfide, while the reaction order of water changes as the reaction conditions change. The controlling steps are also different because the reaction conditions such as concentration of carbonyl sulfide, reaction temperature, water-air ratio, and reaction atmosphere are different. The hydrolysis of carbonyl sulfide is base-catalyzed reaction, and the force of the base site has an important effect on the hydrolysis of carbonyl sulfide. PMID:23956697

  16. Carbonyl-Olefin Exchange Reaction: Present State and Outlook

    NASA Astrophysics Data System (ADS)

    Kalinova, Radostina; Jossifov, Christo

    The carbonyl-olefin exchange reaction (COER) is a new reaction between carbonyl group and olefin double bond, which has a formal similarity with the olefin metathesis (OM) - one carbon atom in the latter is replaced with an oxygen atom. Till now the new reaction is performed successfully only when the two functional groups (carbonyl group and olefin double bond) are in one molecule and are conjugated. The α, β-unsaturated carbonyl compounds (substituted propenones) are the compounds with such a structure. They polymerize giving substituted polyacetylenes. The chain propagation step of this polymerization is in fact the COER. The question arises: is it possible the COER to take place when the two functional groups are not in one molecule and are not conjugated, and could this reaction became an alternative of the existing carbonyl olefination reactions?

  17. Detection of carbonyl fluoride in the stratosphere

    NASA Technical Reports Server (NTRS)

    Rinsland, C. P.; Park, J. H.; Russell, J. M., III; Zander, R.; Brown, L. R.; Farmer, C. B.; Norton, R. H.; Raper, O. F.

    1986-01-01

    Infrared solar absorption spectra of the stratosphere recorded at a resolution of 0.01/cm by the ATMOS (Atmospheric Trace Molecule Spectroscopy) instrument from onboard Spacelab 3 (04/30 to 05/6/85) have revealed the existence of many previously unobserved absorption features in the 1925 to 1960/cm and 1249 to 1255/cm regions and one at 774/cm. On the basis of comparisons with laboratory spectra, these features have been identified as belonging to the nu1, nu4, and nu6 bands of carbonyl fluoride, respectively. Volume mixing ratios of COF2 between 17 and 40 km have been deduced from analysis of the nu1 and nu6 bands.

  18. Atmospheric carbonyl sulfide exchange in bog microcosms

    SciTech Connect

    Fried, A.; Klinger, L.F.; Erickson, D.J. III )

    1993-01-22

    Measurements of Carbonyl sulfide (OCS) fluxes were carried out on bog microcosms using chamber sampling and tunable diode laser analysis. Intact bog microcosms (vascular plants, mosses, and peat) removed ambient levels of OCS in the light and dark with rates from [minus]2.4 to [minus]8.1 ng S min[sup [minus]1] m[sup [minus]2]. Peat and peat plus mosses emitted OCS in the light with rates of 17.4 and 10.9 ng S min[sup [minus]1] m[sup [minus]2], respectively. In the dark, the mosses apparently removed OCS at a rate equivalent to the peat emissions. A 3-D numerical tracer model using this data indicated that boreal bog ecosystems remove at most 1% of ambient OCS, not sufficient to account for an observed OCS depletion in boreal air masses. 13 refs., 1 fig., 1 tab.

  19. Metal-free carbonylations by photoredox catalysis.

    PubMed

    Majek, Michal; Jacobi von Wangelin, Axel

    2015-02-01

    The synthesis of benzoates from aryl electrophiles and carbon monoxide is a prime example of a transition-metal-catalyzed carbonylation reaction which is widely applied in research and industrial processes. Such reactions proceed in the presence of Pd or Ni catalysts, suitable ligands, and stoichiometric bases. We have developed an alternative procedure that is free of any metal, ligand, and base. The method involves a redox reaction driven by visible light and catalyzed by eosin Y which affords alkyl benzoates from arene diazonium salts, carbon monoxide, and alcohols under mild conditions. Tertiary esters can also be prepared in high yields. DFT calculations and radical trapping experiments support a catalytic photoredox pathway without the requirement for sacrificial redox partners.

  20. Reductive carbonylation of aromatic nitro compounds

    SciTech Connect

    Wehman, P.; Kamer, P.C.J.; Leeuwen, P.W.N.M. van

    1995-12-31

    In the reductive carbonylation of aromatic nitro compounds carbamates and isocyanates are prepared through a direct reaction between the nitro group and CO under the influence of a catalyst. This route avoids the major disadvantages of the traditional process for the production of the industrially important isocyanates and carbamates. The authors have developed a stable, active, and rather selective homogeneous palladium catalyst for the reductive carbonylation of the nitro substrate. Best results were obtained with Pd-phenanthroline complexes in which the ligands bear moderately donating substituents. Noncoordinating anions in the catalyst complex are clearly preferable. The highest activity was reached with the Pd(4,7-Me{sub 2}-1,10-phen){sub 2}(OTf){sub 2} catalyst complex (t.o.f. = 311 mol/mol/h, selectivity toward the desired carbamate = 84%). With the Pd(1,10-phenanthroline){sub 2}(OTf){sub 2} catalyst complex, the authors studied the scope of the reaction in order to prepare a wide range of functionalized carbamates for the fine chemistry. During this study, it was found that a remarkable improvement of the catalytic activity and selectivity on addition of a benzoic acid (t.o.f. > 365 mol/mol/h, selectivity toward carbamate = 94%). In the presence of 4-chlorobenzoic acid even aromatic dinitro compounds could be converted easily, resulting in the best results reported ever for the conversion of 1,4-dinitrobenzene into the corresponding dicarbamate (t.o.f. = 73 mol/mol/h, selectivity toward the dicarbamate = 86%).

  1. Gas-phase chemistry of technetium carbonyl complexes.

    PubMed

    Wang, Yang; Qin, Zhi; Fan, Fang-Li; Haba, Hiromitsu; Komori, Yukiko; Cao, Shi-Wei; Wu, Xiao-Lei; Tan, Cun-Min

    2015-05-28

    Gas-phase chemical behaviors of short-lived technetium carbonyl complexes were studied using a low temperature isothermal chromatograph (IC) coupled with a (252)Cf spontaneous fission (SF) source. Fission products recoiled from the (252)Cf SF source were thermalized in a mixed gas containing CO, and then technetium carbonyl complexes were formed from reactions between CO gas and various technetium isotopes. A gas-jet system was employed to transport the volatile carbonyl complexes from a recoil chamber to the IC. Short IC columns made of Fluorinated Ethylene Propylene (FEP) Teflon and quartz were used to obtain chemical information about the technetium carbonyl complexes. The results for the (104)Tc-(106)Tc carbonyl complexes were found to be strongly influenced by the precursors, and showed the chemical behaviors of (104)Mo-(106)Mo carbonyl complexes, respectively. However, (107)Tc and (108)Tc could represent the chemical information of the element technetium due to their high independent yields and the very short half-lives of their precursors (107)Mo and (108)Mo. An adsorption enthalpy of about ΔHads = -43 kJ mol(-1) was determined for the Tc carbonyl complexes on both the Teflon and quartz surfaces by fitting the breakthrough curves of the (107)Tc and (108)Tc carbonyl complexes with a Monte Carlo simulation program. Chemical yields of around 25% were measured for the Tc carbonyl complexes relative to the transport yields obtained with the gas-jet transport of KCl aerosol particles with Ar carrier gas. Furthermore, the influence of a small amount of O2 gas on the yields of the Mo and Tc carbonyl complexes was studied.

  2. Carbonyl emissions from gasoline and diesel motor vehicles.

    PubMed

    Jakober, Chris A; Robert, Michael A; Riddle, Sarah G; Destaillats, Hugo; Charles, M Judith; Green, Peter G; Kleeman, Michael J

    2008-07-01

    Carbonyls from gasoline-powered light-duty vehicles (LDVs) and heavy-duty diesel-powered vehicles (HDDVs) operated on chassis dynamometers were measured by use of an annular denuder-quartz filter-polyurethane foam sampler with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine derivatization and chromatography-mass spectrometry analyses. Two internal standards were utilized based on carbonyl recovery: 4-fluorobenzaldehyde for < C8 carbonyls and 6-fluoro-4-chromanone for > or = C8 compounds. Gas- and particle-phase emissions for 39 aliphatic and 20 aromatic carbonyls ranged from 0.1 to 2000 microg/L of fuel for LDVs and from 1.8 to 27 000 microg/L of fuel for HDDVs. Gas-phase species accounted for 81-95% of the total carbonyls from LDVs and 86-88% from HDDVs. Particulate carbonyls emitted from a HDDV under realistic driving conditions were similar to concentrations measured in a diesel particulate matter (PM) standard reference material. Carbonyls accounted for 19% of particulate organic carbon (POC) emissions from low-emission LDVs and 37% of POC emissions from three-way catalyst-equipped LDVs. This identifies carbonyls as one of the largest classes of compounds in LDV PM emissions. The carbonyl fraction of HDDV POC was lower, 3.3-3.9% depending upon operational conditions. Partitioning analysis indicates the carbonyls had not achieved equilibrium between the gas and particle phases under the dilution factors of 126-584 used in the present study. PMID:18677993

  3. Gas-phase chemistry of technetium carbonyl complexes.

    PubMed

    Wang, Yang; Qin, Zhi; Fan, Fang-Li; Haba, Hiromitsu; Komori, Yukiko; Cao, Shi-Wei; Wu, Xiao-Lei; Tan, Cun-Min

    2015-05-28

    Gas-phase chemical behaviors of short-lived technetium carbonyl complexes were studied using a low temperature isothermal chromatograph (IC) coupled with a (252)Cf spontaneous fission (SF) source. Fission products recoiled from the (252)Cf SF source were thermalized in a mixed gas containing CO, and then technetium carbonyl complexes were formed from reactions between CO gas and various technetium isotopes. A gas-jet system was employed to transport the volatile carbonyl complexes from a recoil chamber to the IC. Short IC columns made of Fluorinated Ethylene Propylene (FEP) Teflon and quartz were used to obtain chemical information about the technetium carbonyl complexes. The results for the (104)Tc-(106)Tc carbonyl complexes were found to be strongly influenced by the precursors, and showed the chemical behaviors of (104)Mo-(106)Mo carbonyl complexes, respectively. However, (107)Tc and (108)Tc could represent the chemical information of the element technetium due to their high independent yields and the very short half-lives of their precursors (107)Mo and (108)Mo. An adsorption enthalpy of about ΔHads = -43 kJ mol(-1) was determined for the Tc carbonyl complexes on both the Teflon and quartz surfaces by fitting the breakthrough curves of the (107)Tc and (108)Tc carbonyl complexes with a Monte Carlo simulation program. Chemical yields of around 25% were measured for the Tc carbonyl complexes relative to the transport yields obtained with the gas-jet transport of KCl aerosol particles with Ar carrier gas. Furthermore, the influence of a small amount of O2 gas on the yields of the Mo and Tc carbonyl complexes was studied. PMID:25920667

  4. Carbonyl Emissions From Oil and Gas Production Facilities

    NASA Astrophysics Data System (ADS)

    Lyman, S. N.; O'Neil, T.; Tran, T.

    2015-12-01

    A number of recent studies have targeted emissions of methane and other hydrocarbons from oil and gas exploration and production activity. These measurements are greatly increasing understanding of the atmospheric impacts of oil and gas development. Very few measurements exist, however, of emissions of formaldehyde and other carbonyls from oil and gas equipment. Carbonyls are toxic and serve as important ozone precursors, especially during winter ozone episodes in places like Utah's Uintah Basin. Current air quality models are only able to reproduce observed high wintertime ozone if they incorporate emissions inventories with very high carbonyl emissions. We measured carbonyl emissions from oil and gas equipment and facilities—including glycol dehydrators, liquid storage tanks, raw gas leaks, raw gas-burning engines, and produced water surface impoundments—in Rocky Mountain oil and gas fields. Carbonyl emissions from raw gas were below detection, but emissions of formaldehyde, acetaldehyde, and other carbonyls were detected from liquid storage tanks, glycol dehydrators, and other oil and gas equipment. In some cases, carbonyls may be formed from the degradation of methanol and other chemicals used in oil and gas production, but the collected data provide evidence for other non-combustion formation pathways. Raw gas-burning engines also emitted carbonyls. Emissions from all measured sources were a small fraction of total volatile organic compound emissions. We incorporated our measurements into an emissions inventory, used that inventory in an air quality model (WRF-SMOKE-CAMx), and were unable to reproduce observed high wintertime ozone. This could be because (1) emission sources we have not yet measured, including compressors, gas processing plants, and others, are large; (2) non-carbonyl emissions, especially those that quickly degrade into carbonyls during photochemical processing, are underestimated in the inventory; or (3) the air quality model is unable

  5. Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors.

    PubMed

    Xu, Changqing; Cui, Changhai; Alkon, Daniel L

    2009-08-01

    Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24-26 months old) and young (2-4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline. PMID:19123252

  6. Age-dependent changes in material properties of the brain and braincase of the rat.

    PubMed

    Gefen, Amit; Gefen, Nurit; Zhu, Qiliang; Raghupathi, Ramesh; Margulies, Susan S

    2003-11-01

    Clinical and biomechanical evidence indicates that mechanisms and pathology of head injury in infants and young children may be different from those in adults. Biomechanical computer-based modeling, which can be used to provide insight into the thresholds for traumatic tissue injury, requires data on material properties of the brain, skull, and sutures that are specific for the pediatric population. In this study, brain material properties were determined for rats at postnatal days (PND) 13, 17, 43, and 90, and skull/suture composite (braincase) properties were determined at PND 13, 17, and 43. Controlled 1 mm indentation of a force probe into the brain was used to measure naive, non-preconditioned (NPC) and preconditioned (PC) instantaneous (G(i)) and long-term (G( infinity )) shear moduli of brain tissue both in situ and in vitro. Brains at 13 and 17 PND exhibited statistically indistinguishable shear moduli, as did brains at 43 and 90 PND. However, the immature (average of 13 and 17 PND) rat brain (G(i) = 3336 Pa NPC, 1754 Pa PC; G( infinity )= 786 Pa NPC, 626 Pa PC) was significantly stiffer (p < 0.05) than the mature (average of 43 and 90 PND) brains (G(i) = 1721 Pa NPC, 1232 Pa PC; G( infinity ) = 508 Pa NPC, 398 Pa PC). A "reverse engineering" finite element model approach, which simulated the indentation of the force probe into the intact braincase, was used to estimate the effective elastic moduli of the braincase. Although the skull of older rats was significantly thicker than that of the younger rats, there was no significant age-dependent change in the effective elastic modulus of the braincase (average value = 6.3 MPa). Thus, the increase in structural rigidity of the braincase with age (up to 43 PND) was due to an increase in skull thickness rather than stiffening of the tissue. These observations of a stiffer brain and more compliant braincase in the immature rat compared with the adult rat will aid in the development of age-specific experimental

  7. Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

    PubMed Central

    Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

    2015-01-01

    renal function. Free ASARM-peptide also effects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments. PMID:26051469

  8. From CIE 2006 physiological model to improved age-dependent and average colorimetric observers.

    PubMed

    Sarkar, Abhijit; Autrusseau, Florent; Viénot, Françoise; Le Callet, Patrick; Blondé, Laurent

    2011-10-01

    the source of these prediction errors at higher wavelengths. Correcting these errors in the model can lead to an improved age-dependent observer and can also help update the current CIE 10° standard colorimetric observer. Accordingly, it would reduce the discrepancies between color matches with broadband spectral primaries and color matches with narrowband spectral primaries.

  9. The short-term effects of soybean intake on oxidative and carbonyl stress in men and women.

    PubMed

    Celec, Peter; Hodosy, Július; Pálffy, Roland; Gardlík, Roman; Halčák, Lukáč; Ostatníková, Daniela

    2013-01-01

    Beyond other beneficial effects, a soy-rich diet has been shown to reduce the risk of cardiovascular diseases and diabetic complications. Reduction of oxidative and carbonyl stress has been proposed as the underlying mechanism, but the evidence for this is lacking. The aim of our study was to evaluate the effects of short-term increased soy intake on oxidative and carbonyl stress parameters in young volunteers. Young healthy probands (omnivores) of both genders (55 women, 33 men) were given soybeans (2 g/kg bodyweight daily) for one week. Markers of oxidative and carbonyl stress were measured in plasma at the beginning and at the end of one week soybean intake and after another week of a wash-out period. Total antioxidant capacity was increased by soybean intake in both genders. This led to decreased levels of advanced oxidation protein products in women, but not in men. On the contrary, in men, soybean intake increased lipoperoxidation. No effects on carbonyl stress markers (advanced glycation end products-specific fluorescence and fructosamine) were found. Soybean intake has gender-specific effects on oxidative stress in young healthy probands potentially due to divergent action and metabolism of phytoestrogens in men and women. Effects of soybean intake on carbonyl stress should be evaluated in longer studies.

  10. Synthesis and in vivo evaluation of the putative breast cancer resistance protein inhibitor [11C]methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl)phenyl)amino-carbonyl)-2-(quinoline-2-carbonylamino)benzoate

    PubMed Central

    Mairinger, Severin; Langer, Oliver; Kuntner, Claudia; Wanek, Thomas; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Dörner, Bernd; Bauer, Florian; Baumgartner, Christoph; Löscher, Wolfgang; Erker, Thomas; Müller, Markus

    2013-01-01

    Introduction The multidrug efflux transporter breast cancer resistance protein (BCRP) is highly expressed in the blood-brain barrier (BBB), where it limits brain entry of a broad range of endogenous and exogenous substrates. Methyl 4-((4-(2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl)phenyl)amino-carbonyl)-2-(quinoline-2-carbonylamino)benzoate (1) is a recently discovered BCRP-selective inhibitor, which is structurally derived from the potent P-glycoprotein (P-gp) inhibitor tariquidar. The aim of this study was to develop a new PET tracer based on 1 to map BCRP expression levels in vivo. Methods 1 was labelled with 11C in its methyl ester function by reaction of the corresponding carboxylic acid 2 with [11C]methyl triflate. PET imaging of [11C]-1 was performed in wild-type, Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice (n=3 per mouse type) and radiotracer metabolism was assessed in plasma and brain. Results Brain-to-plasma ratios of unchanged [11C]-1 were 4.8- and 10.3-fold higher in Mdr1a/b(−/−) and in Mdr1a/b(−/−)Bcrp1(−/−) mice, respectively, as compared to wild-type animals, but only modestly increased in Bcrp1(−/−) mice. [11C]-1 was rapidly metabolized in vivo giving rise to a polar radiometabolite which was taken up into brain tissue. Conclusion Our data suggest that [11C]-1 preferably interacts with P-gp rather than BCRP at the murine BBB which questions its reported in vitro BCRP selectivity. Consequently, [11C]-1 appears to be unsuitable as a PET tracer to map cerebral BCRP expression. PMID:20610168

  11. Seasonal and diurnal characteristics of atmospheric carbonyls in Nanning, China

    NASA Astrophysics Data System (ADS)

    Guo, Songjun; Chen, Mei; Tan, Jihua

    2016-03-01

    For the first time, atmospheric carbonyls were measured to identify seasonal and diurnal variations in Nanning from October 2011 to July 2012. Formaldehyde (6.79 ± 3.39 μg/m3), acetaldehyde (15.81 ± 10.48 μg/m3) and acetone (5.43 ± 6.91 μg/m3) were the three most abundant carbonyls, accounting for ~ 85% of the total carbonyls. The average total concentrations of carbonyls and three abundant carbonyls showed significant high levels in summer compared to those in winter. Diurnal variations suggested that photochemical conditions, combustion of charcoal and straw, and solvent usage are important for the distributions of atmospheric carbonyls. The highest average C1/C2 ratio was observed in summer (0.75) compared to those (0.31-0.70) in other seasons, implying the positive effect of photochemical activities on raising C1/C2 ratio, and the significant low C2/C3 ratio (12.01-18.23) in winter and autumn than those (95.83-24.49) in both spring and summer suggested the important anthropogenic emissions such as charcoal and biomass combustion. O3 formation potentials in summer and spring were significantly higher by ~ 2 times than those in autumn and winter. Formaldehyde and acetaldehyde are the top two carbonyls which contribute 82-97% to total O3 formation potentials.

  12. Protection against Photooxidative Injury of Tobacco Leaves by 2-Alkenal Reductase. Detoxication of Lipid Peroxide-Derived Reactive Carbonyls1

    PubMed Central

    Mano, Jun'ichi; Belles-Boix, Enric; Babiychuk, Elena; Inzé, Dirk; Torii, Yoshimitsu; Hiraoka, Eiji; Takimoto, Koichi; Slooten, Luit; Asada, Kozi; Kushnir, Sergei

    2005-01-01

    Degradation of lipid peroxides leads to the formation of cytotoxic 2-alkenals and oxenes (collectively designated reactive carbonyls). The novel NADPH-dependent oxidoreductase 2-alkenal reductase (AER; EC 1.3.1.74) from Arabidopsis (Arabidopsis thaliana), which is encoded by the gene At5g16970, catalyzes the reduction of the α,β-unsaturated bond of reactive carbonyls, and hence is presumed to function in antioxidative defense in plants. Here we show that Arabidopsis AER (At-AER) has a broad substrate spectrum to biologically relevant reactive carbonyls. Besides 2-alkenals, the enzyme recognized as substrates the lipid peroxide-derived oxenes 9-oxo-octadeca-(10E),(12Z)-dienoic acid and 13-oxo-octadeca-(9E),(11Z)-dienoic acid, as well as the potent genotoxin 4-oxo-(2E)-nonenal, altogether suggesting AER has a key role in the detoxification of reactive carbonyls. To validate this conclusion by in vivo studies, transgenic tobacco (Nicotiana tabacum) plants that had 100- to 250-fold higher AER activity levels than control plants were generated. The engineered plants exhibited significantly less damage from either (1) the exogenously administered 4-hydroxy-(2E)-nonenal, (2) treatment with methyl viologen plus light, or (3) intense light. We further show that the At-AER protein fused with the Aequorea victoria green fluorescent protein localizes in cytosol and the nucleus in Bright-Yellow 2 cells. These results indicate that reactive carbonyls mediate photooxidative injury in leaf cells, and At-AER in the cytosol protects the cells by reducing the α,β-unsaturated bond of the photoproduced reactive carbonyls. PMID:16299173

  13. [Age-dependent characteristics of nutritional status and resting metabolism in overweight and obese children].

    PubMed

    Pavlovskaia, E V; Strokova, T V; Surkov, A G; Bogdanov, A R; Borodina, G V; Kutyreva, E N; Sentsova, T B

    2014-01-01

    The age-dependent nutritional status and resting metabolism in overweight and obese children have been examined. The study included 625 children of 2.5-17 years old. Patients were divided into three groups: 1st--2.5-7 years old (n = 49), 2nd--8-12 years old (n = 204), 3rd--13-17 years old (n = 372). The diagnosis of overweight and obesity was based on CDC criteria: children with 85-94 BMI percentile according to age and gender had overweight, BMI 295 percentile--obesity. Anthropometry, bioelectric impedance analysis and indirect respiratory calorimetry were performed; lipid and carbohydrate parameters were measured. The fat mass percentages in children of studed groups were 41.3 ± 1.9, 39.8 ± 0.7 and 42.3 ± 0.4%, the mean percent of fat mass excess--163.6 ± 26.2, 113.7 ± 8.3 and 134.9 ± 8.2% respectively, p > 0.05. Prevalence of dyslipidemia in children increased with age: lipid metabolism disorders were revealed in 28.6, 49.0 u 53.2% children of the 1st, 2nd and 3rd groups respectively. The mean HDL level in the 1st and 2nd groups was significantly higher, and triglycerides--lower than in the 3rd group. The correlation of HDL level and breastfeeding duration (r1 = 0.94, p < 0.05) was found in the 1st group of children. Increased insulin level was revealed in 38.8% children in the 1st group (mean 12.8 ± 1.4 μIU/ml), 62.2% children in the 2nd group (21.1 ± 0.7 μIU/ml) and 64.8% children in the 3rd group (25.1 ± 0.9 μIU/ml); increased HOMA--in 36.7% (4.32 ± 0.6), 62.2% (4.65 ± 0.17) and 59.1% (5.56 ± 0.21) respectively. The negative correlation of insulin and HOMA level with breastfeeding duration (r1 = -0.38 and -0.37, respectively, p < 0.05) was found in the 1st group of children. Prevalence of hyperuricemia increased from 13% in the 1st group to 21.1% in the 2nd and 44.1% in the 3rd group. Prevalence and degree of resting metabolism changes increased with age and had tendency to the shift of proportion of energy-intensive substrates (fats and

  14. Interdisciplinary neurotoxicity inhalation studies: Carbon disulfide and carbonyl sulfide research in F344 rats

    SciTech Connect

    Sills, Robert C. . E-mail: sills@niehs.nih.gov; Harry, G. Jean; Valentine, William M.; Morgan, Daniel L.

    2005-09-01

    Inhalation studies were conducted on the hazardous air pollutants, carbon disulfide, which targets the central nervous system (spinal cord) and peripheral nervous system (distal portions of long myelinated axons), and carbonyl sulfide, which targets the central nervous system (brain). The objectives were to investigate the neurotoxicity of these compounds by a comprehensive evaluation of function, structure, and mechanisms of disease. Through interdisciplinary research, the major finding in the carbon disulfide inhalation studies was that carbon disulfide produced intra- and intermolecular protein cross-linking in vivo. The observation of dose-dependent covalent cross-linking in neurofilament proteins prior to the onset of lesions is consistent with this process contributing to the development of the neurofilamentous axonal swellings characteristic of carbon disulfide neurotoxicity. Of significance is that valine-lysine thiourea cross-linking on rat globin and lysine-lysine thiourea cross-linking on erythrocyte spectrin reflect cross-linking events occurring within the axon and could potentially serve as biomarkers of carbon disulfide exposure and effect. In the carbonyl sulfide studies, using magnetic resonance microscopy (MRM), we determined that carbonyl sulfide targets the auditory pathway in the brain. MRM allowed the examination of 200 brain slices and made it possible to identify the most vulnerable sites of neurotoxicity, which would have been missed in our traditional neuropathology evaluations. Electrophysiological studies were focused on the auditory system and demonstrated decreases in auditory brain stem evoked responses. Similarly, mechanistic studies focused on evaluating cytochrome oxidase activity in the posterior colliculus and parietal cortex. A decrease in cytochrome oxidase activity was considered to be a contributing factor to the pathogenesis of carbonyl sulfide neurotoxicity.

  15. Investigation of carbonyl compounds in bottled waters from Poland.

    PubMed

    Nawrocki, J; Dabrowska, A; Borcz, A

    2002-11-01

    Poly(ethylene terephtalate) (PET) bottles are commonly used for storing mineral water. The migration of carbonyl compounds from PET bottles into mineral water was observed. Carbonation of water, sunlight and high temperature enhance the process of migration. Formaldehyde, acetaldehyde and acetone were the most important carbonyls identified in series of bottled water samples. The concentration of carbonyls can change depending on the time of storage as well as storage conditions. It was identified particularly high concentration of acetaldehyde (more than 100 microg 1(-1)) in samples of mineral water saturated with CO2 gas. PMID:12448533

  16. Age-dependent capacity to accelerate protein synthesis dictates the extent of compensatory growth in skeletal muscle following undernutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In both humans and animals, impaired growth during early life compromises adult lean body mass and muscle strength despite skeletal muscle’s large regenerative capacity. To identify the significance of developmental age on skeletal muscle’s capacity for catch-up growth following an episode of under ...

  17. Assignment of congested NMR spectra: Carbonyl backbone enrichment via the Entner Doudoroff pathway

    NASA Astrophysics Data System (ADS)

    Goldbourt, Amir; Day, Loren A.; McDermott, Ann E.

    2007-12-01

    In NMR spectra of complex proteins, sparse isotope enrichment can be important, in that the removal of many 13C- 13C homonuclear J-couplings can narrow the lines and thereby facilitate the process of spectral assignment and structure elucidation. We present a simple scheme for selective yet extensive isotopic enrichment applicable for production of proteins in organisms utilizing the Entner-Doudoroff (ED) metabolic pathway. An enrichment scheme so derived is demonstrated in the context of a magic-angle spinning solid-state NMR (MAS SSNMR) study of Pf1 bacteriophage, the host of which is Pseudomonas aeruginosa, strain K (PAK), an organism that uses the ED pathway for glucose catabolism. The intact and infectious Pf1 phage in this study was produced by infected PAK cells grown on a minimal medium containing 1- 13C D-glucose ( 13C in position 1) as the sole carbon source, as well as 15NH 4Cl as the only nitrogen source. The 37 MDa Pf1 phage consists of about 93% major coat protein, 1% minor coat proteins, and 6% single-stranded, circular DNA. As a consequence of this composition and the enrichment scheme, the resonances in the MAS SSNMR spectra of the Pf1 sample were almost exclusively due to carbonyl carbons in the major coat protein. Moreover, 3D heteronuclear NCOCX correlation experiments also show that the amino acids leucine, serine, glycine, and tyrosine were not isotopically enriched in their carbonyl positions (although most other amino acids were), which is as expected based upon considerations of the ED metabolic pathway. 3D NCOCX NMR data and 2D 15N- 15N data provided strong verification of many previous assignments of 15N amide and 13C carbonyl shifts in this highly congested spectrum; both the semi-selective enrichment patterns and the narrowed linewidths allowed for greater certainty in the assignments as compared with use of uniformly enriched samples alone.

  18. Deposition of carbonyl sulphide to soils

    NASA Astrophysics Data System (ADS)

    Kluczewski, S. M.; Brown, K. A.; Bel, J. N. B.

    Carbonyl sulphide (COS) is a trace constituent of the atmosphere and is also the main form in which 35S is released from CO 2-cooled nuclear reactors. Measurements of its deposition velocity ( Vg) are therefore important for validating radiological dose models and for interpreting the role of COS in the global S cycle. The Vg of [ 35S]COS to thin layers of several contrasting soils was measured in a through-flow fumigation system. Deposition velocity was not significantly affected by soil type, although deposition to moist soil was significantly greater ( P < 0.001) than for air-dried soils, mean values being 5.71 × 10 -6 ms -1 and 3.06 × 10 -6 ms -1, respectively. The results obtained are about three orders of magnitude smaller than published Vg values for SO 2 to similar soils, which suggests that uptake by soils is not a major sink for atmospheric COS. The results are consistent with the hypothesis that deposition to soil of [ 35S]COS from nuclear reactors is unlikely to contribute significantly to radiation dose from the food chain pathway. The reduction in Vg observed in heat-treated soils indicates a microbial involvement in uptake. However, it seems unlikely that microbial metabolism is the rate-controlling step, since stimulation of the microflora by the addition of nutrients did not increase COS deposition.

  19. Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

    PubMed Central

    Singh, Mahavir; Kapoor, Aniruddh; Bhatnagar, Aruni

    2015-01-01

    Extensive research has shown that increased production of reactive oxygen species (ROS) results in tissue injury under a variety of pathological conditions and chronic degenerative diseases. While ROS are highly reactive and can incite significant injury, polyunsaturated lipids in membranes and lipoproteins are their main targets. ROS-triggered lipid peroxidation reactions generate a range of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2-nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and phospholipid aldehydes have been shown to be produced under conditions of oxidative stress and contribute to tissue injury and dysfunction by depleting glutathione and other reductants leading to the modification of proteins, lipids, and DNA. To prevent tissue injury, these RCS are metabolized by several oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily, aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism via these enzymes results in RCS inactivation and detoxification, although under some conditions, it can also lead to the generation of signaling molecules that trigger adaptive responses. Metabolic transformation and detoxification of RCS by oxidoreductases prevent indiscriminate ROS toxicity, while at the same time, preserving ROS signaling. A better understanding of RCS metabolism by oxidoreductases could lead to the development of novel therapeutic interventions to decrease oxidative injury in several disease states and to enhance resistance to ROS-induced toxicity. PMID:25559856

  20. The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model.

    PubMed

    Chiba, Yoichi; Shimada, Atsuyoshi; Kumagai, Naoko; Yoshikawa, Keisuke; Ishii, Sanae; Furukawa, Ayako; Takei, Shiro; Sakura, Masaaki; Kawamura, Noriko; Hosokawa, Masanori

    2009-04-01

    The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions. PMID:18688709

  1. Growth activity in human septal cartilage: age-dependent incorporation of labeled sulfate in different anatomic locations

    SciTech Connect

    Vetter, U.; Pirsig, W.; Heinze, E.

    1983-02-01

    Growth activity in different areas of human septal cartilage was measured by the in vitro incorporation of /sup 35/S-labeled NaSO/sub 4/ into chondroitin sulfate. Septal cartilage without perichondrium was obtained during rhinoplasty from 36 patients aged 6 to 35 years. It could be shown that the anterior free end of the septum displays high growth activity in all age groups. The supra-premaxillary area displayed its highest growth activity during prepuberty, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in growth activity was found in the caudal prolongation of the septal cartilage. No age-dependent variations could be detected in the posterior area of the septal cartilage.

  2. 31P{1H}NMR and carbonyl force constants of unsymmetrical bidentate phosphine complexes of group (VI) metal carbonyls

    NASA Astrophysics Data System (ADS)

    Jesu Raj, Joe Gerald; Pathak, Devendra Deo; Kapoor, Pramesh N.

    2015-05-01

    In our present work we report synthesis of an unsymmetrical diphos ligand, 1-diphenylphosphino-2-di-m-tolylphosphinoethane and its coordinate complexes with group (VI) metal carbonyls such as Cr(CO)6 Mo(CO)6 and W(CO)6. The synthesized ligand and its complexes have been completely characterized by elemental analyses, FTIR, 1HNMR, 31P{1H}NMR and FAB mass spectrometry methods. Special emphasis has been given to calculations of carbonyl force constants. Based on the spectroscopic evidences it has been confirmed that these metal carbonyl complexes with the ditertiary phosphine ligand showed cis geometry in their molecular structure.

  3. Microsurgeons do better--tactile training might prevent the age-dependent decline of the sensibility of the hand.

    PubMed

    Schmauss, Daniel; Megerle, Kai; Weinzierl, Andrea; Agua, Kariem; Cerny, Michael; Schmauss, Verena; Lohmeyer, Joern A; Machens, Hans-Guenther; Erne, Holger

    2015-12-01

    Recent data demonstrate that the normal sensibility of the hand seems to be age-dependent with the best values in the third decade and a consecutive deterioration afterwards. However, it is not clear if long-term tactile training might prevent this age-dependent decline. We evaluated sensibility of the hand in 125 surgeons aged between 26 and 75 years who perform microsurgical operations, thereby undergoing regular tactile training. We examined sensibility of the radial digital nerve of the index finger (N3) and the ulnar digital nerve of the small finger (N10) using static and moving two-point discrimination (2PD) tests and compared the results to 154 age-matched individuals without specific long-term tactile training. We found significantly lower static and moving 2PD values for the sixth, seventh, and eighth decade of life in the microsurgery group compared to the control group (p < 0.05). This study demonstrates that long-term tactile training might prevent the known age-dependent decline of the sensibility of the hand.

  4. Evidence for age-dependent changes in Sertoli cell androgen receptor concentration.

    PubMed

    Buzek, S W; Caston, L A; Sanborn, B M

    1987-01-01

    Cytosol and nuclear receptor concentrations in Sertoli cells isolated from the testes of 15-, 25-, and 35-day-old rats were measured using hydroxylapatite separation procedures. In these cells the mean Kd of the cytosol receptor for methyltrienolone (3H-R1881) ranged between 2.3 and 2.9 nM, and the concentration of cytosol androgen receptor per mg Sertoli cell DNA increased over the 15-to 35-day age interval. However, when the data were expressed per mg cytosol protein, no increase was observed. The increase in receptor concentration per mg DNA paralleled the increase in cytosol protein/DNA ratio. The concentration of androgen receptor per mg DNA in nuclear extracts also increased with age. Consequently, total Sertoli cell androgen receptor increases over the time interval in which meiosis is first completed in the testis.

  5. Carbonyl-Olefin Exchange Reaction and Related Chemistry

    NASA Astrophysics Data System (ADS)

    Jossifov, Christo; Kalinova, Radostina

    A new carbon—carbon double bond forming reaction (carbonyl olefin exchange reaction) mediated by transition metal catalytic systems has been discovered. The catalytic systems used (transition metal halides or oxohalides alone or in combination with Lewis acids) are active only in the case when the two reacting groups are in one molecules and are conjugated. In addition these systems accelerate other reactions which run simultaneously with the carbonyl olefin metathesis rendering a detailed investigation of the process very complicated.

  6. [Defects in TOR regulatory complexes retard aging and carbonyl/oxidative stress development in yeast Saccharomyces cerevisiae].

    PubMed

    Homza, B V; Vasyl'kovs'ka, R A; Semchyshyn, H M

    2014-01-01

    TOR signaling pathway first described in yeast S. cerevisiae is the highly conserved regulator of eukaryotic cell growth, aging and stress resistance. The effect of nitrogen sources, in particular amino acids, on the activity of TOR signaling pathway is well studied, however its relation to carbohydrates is poor understood. The aim of the present study is expanding of our understanding of potential role of TOR regulatory complexes in development of carbonyl/oxidative stress that can result from yeast cultivation on glucose and fructose. It has been shown that the level of alpha-dicarbonyl compounds and protein carbonyl groups increased with time of yeast cultivation and was higher in cells grown on fructose that demonstrated their accelerated aging and carbonyl/oxidative stress development as compared with cells grown on glucose. The strains defective in TOR proteins cultivated in the presence of glucose as well as fructose demonstrated lower markers of the stress and aging than parental strain. Thus these data confirmed the previous conclusion on fructose more potent ability to cause carbonyl/oxidative stress and accelerated aging in S. cerevisiae as compared with glucose. However, defects in TOR regulatory complexes retard aging and development of the stress in yeast independent on the type of carbohydrate in the cultivation medium.

  7. [Defects in TOR regulatory complexes retard aging and carbonyl/oxidative stress development in yeast Saccharomyces cerevisiae].

    PubMed

    Homza, B V; Vasyl'kovs'ka, R A; Semchyshyn, H M

    2014-01-01

    TOR signaling pathway first described in yeast S. cerevisiae is the highly conserved regulator of eukaryotic cell growth, aging and stress resistance. The effect of nitrogen sources, in particular amino acids, on the activity of TOR signaling pathway is well studied, however its relation to carbohydrates is poor understood. The aim of the present study is expanding of our understanding of potential role of TOR regulatory complexes in development of carbonyl/oxidative stress that can result from yeast cultivation on glucose and fructose. It has been shown that the level of alpha-dicarbonyl compounds and protein carbonyl groups increased with time of yeast cultivation and was higher in cells grown on fructose that demonstrated their accelerated aging and carbonyl/oxidative stress development as compared with cells grown on glucose. The strains defective in TOR proteins cultivated in the presence of glucose as well as fructose demonstrated lower markers of the stress and aging than parental strain. Thus these data confirmed the previous conclusion on fructose more potent ability to cause carbonyl/oxidative stress and accelerated aging in S. cerevisiae as compared with glucose. However, defects in TOR regulatory complexes retard aging and development of the stress in yeast independent on the type of carbohydrate in the cultivation medium. PMID:24834721

  8. Ecosystem photosynthesis inferred from measurements of carbonyl sulphide flux

    NASA Astrophysics Data System (ADS)

    Asaf, David; Rotenberg, Eyal; Tatarinov, Fyodor; Dicken, Uri; Montzka, Stephen A.; Yakir, Dan

    2013-03-01

    Limited understanding of carbon dioxide sinks and sources on land is often linked to the inability to distinguish between the carbon dioxide taken up by photosynthesis, and that released by respiration. Carbonyl sulphide, a sulphur-containing analogue of carbon dioxide, is also taken up by plants, and could potentially serve as a powerful proxy for photosynthetic carbon dioxide uptake, which cannot be directly measured above the leaf scale. Indeed, variations in atmospheric concentrations of carbonyl sulphide are closely related to those of carbon dioxide at regional, local and leaf scales. Here, we use eddy covariance and laser spectroscopy to estimate the net exchange of carbon dioxide and carbonyl sulphide across three pine forests, a cotton field and a wheat field in Israel. We estimate gross primary productivity--a measure of ecosystem photosynthesis--directly from the carbonyl sulphide fluxes, and indirectly from carbon dioxide fluxes. The two estimates agree within an error of +/-15%. The ratio of carbonyl sulphide to carbon dioxide flux at the ecosystem scale was consistent with the variability in mixing ratios observed on seasonal timescales in the background atmosphere. We suggest that atmospheric measurements of carbonyl sulphide flux could provide an independent constraint on estimates of gross primary productivity, key to projecting the response of the land biosphere to climate change.

  9. Carbonyl species characteristics during the evaporation of essential oils

    NASA Astrophysics Data System (ADS)

    Chiang, Hsiu-Mei; Chiu, Hua-Hsien; Lai, Yen-Ming; Chen, Ching-Yen; Chiang, Hung-Lung

    2010-06-01

    Carbonyls emitted from essential oils can affect the air quality when they are used in indoors, especially under poor ventilation conditions. Lavender, lemon, rose, rosemary, and tea tree oils were selected as typical and popular essential oils to investigate in terms of composition, thermal characteristics and fifteen carbonyl constituents. Based on thermogravimetric (TG) analysis, the activation energy was 7.6-8.3 kcal mol -1, the reaction order was in the range of 0.6-0.7 and the frequency factor was 360-2838 min -1. Formaldehyde, acetaldehyde, acetone, and propionaldehyde were the dominant carbonyl compounds, and their concentrations were 0.034-0.170 ppm. The emission factors of carbonyl compounds were 2.10-3.70 mg g -1, and acetone, propionaldehyde, acetaldehyde, and formaldehyde accounted for a high portion of the emission factor of carbonyl compounds in essential oil exhaust. Some unhealthy carbonyl species such as formaldehyde and valeraldehyde, were measured at low-temperature during the vaporization of essential oils, indicating a potential effect on indoor air quality and human health.

  10. Aldehyde dehydrogenase 2 activation in aged heart improves the autophagy by reducing the carbonyl modification on SIRT1

    PubMed Central

    Li, Chen; Yin, Yue; Yang, Jingrun; Wang, Zhifa; Zheng, Qiangsun; Ma, Heng

    2016-01-01

    Cardiac aging is characterized by accumulation of damaged proteins and decline of autophagic efficiency. Here, by forestalling SIRT1 carbonylated inactivation in aged heart, we determined the benefits of activation of aldehyde dehydrogenase 2 (ALDH2) on the autophagy. In this study, the ALDH2 KO mice progressively developed age-related heart dysfunction and showed reduction in the life span, which strongly suggests that ALDH2 ablation leads to cardiac aging. What's more, aged hearts displayed a significant decrease ALDH2 activity, resulting in accumulation of 4-HNE-protein adducts and protein carbonyls, impairment in the autophagy flux, and, consequently, deteriorated cardiac function after starvation. Sustained Alda-1 (selective ALDH2 activator) treatment increased cardiac ALDH2 activity and abrogated these effects. Using SIRT1 deficient heterozygous (Sirt1+/−) mice, we found that SIRT1 was necessary for ALDH2 activation-induced autophagy. We further demonstrated that ALDH2 activation attenuated SIRT1 carbonylation and improved SIRT1 activity, thereby increasing the deacetylation of nuclear LC3 and FoxO1. Sequentially, ALDH2 enhanced SIRT1 regulates LC3-Atg7 interaction and FoxO1 increased Rab7 expression, which were both necessary and sufficient for restoring autophagy flux. These results highlight that both accumulation of proteotoxic carbonyl stress linkage with autophagy decline contribute to heart senescence. ALDH2 activation is adequate to improve the autophagy flux by reducing the carbonyl modification on SIRT1, which in turn plays an important role in maintaining cardiac health during aging. PMID:26741505

  11. Age-dependent changes in expression of alpha/sub 1/-adrenergic receptors in rat myocardium

    SciTech Connect

    Schaffer, W.; Williams, R.S.

    1986-07-16

    The expression of alpha/sub 1/-adrenergic receptors within ventricular myocardium of rats ranging in age from 21 days of fetal life to 24 months after birth was measured from (/sup 125/I) 2-(..beta.. hydroxy phenyl) ethylaminomethyl tetralone binding isotherms. No difference was observed in binding affinity between any of the age groups studied. The number of alpha/sub 1/-adrenergic receptors was found to be 60-120% higher in membranes from fetal or immature rats up to 25 days of age when compared with adult animals. The increased expression of alpha/sub 1/-adrenergic receptors in the developing heart relative to that observed in adult heart is consistent with the hypothesis that alpha/sub 1/-adrenergic receptor stimulation may modulate protein synthesis and growth in mammalian myocardium.

  12. Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

    PubMed

    Andrews, Melissa R; Soleman, Sara; Cheah, Menghon; Tumbarello, David A; Mason, Matthew R J; Moloney, Elizabeth; Verhaagen, Joost; Bensadoun, Jean-Charles; Schneider, Bernard; Aebischer, Patrick; Fawcett, James W

    2016-01-01

    The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype. PMID:27570822

  13. Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent

    PubMed Central

    Soleman, Sara; Mason, Matthew R. J.; Verhaagen, Joost; Bensadoun, Jean-Charles; Aebischer, Patrick

    2016-01-01

    The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype. PMID:27570822

  14. Carbonyl emissions from vehicular exhausts sources in Hong Kong.

    PubMed

    Ho, Steven Sai Hang; Ho, Kin Fai; Lee, Shun Cheng; Cheng, Yan; Yu, Jian Zhen; Lam, Ka Man; Feng, Natale Sin Yau; Huang, Yu

    2012-02-01

    Vehicular emission (VE) is one of the important anthropogenic sources for airborne carbonyls in urban area. Six types of VE-dominated samples were collected at representative locations in Hong Kong where polluted by a particular fueled type of vehicles, including (i) a gas refilling taxis station (liquefied petroleum gas [LPG] emission); (ii) a light-duty passenger car park (gasoline emission); (iii) a minibus station (diesel emission); (iv) a single-deck-bus depot (diesel emission); (v) a double-deck-bus depot (diesel emission); and (vi) a whole-food market entrance for light- and heavy-duty vehicles (diesel emission). A total of 15 carbonyls in the samples were quantified. Formaldehyde was the most abundant carbonyl among the VE-dominated samples, and its contribution to the total quantified amount on a molar basis ranged from 54.8% to 60.8%. Acetaldehyde and acetone were the next two abundant carbonyls. The carbonyls were quantified at three roadside locations in Hong Kong. The highest concentrations of formaldehyde and acetaldehyde, 22.7 +/- 8.4 and 6.0 +/- 2.8 microg/m3, respectively, were determined in the samples collected at a main transportation gate for goods between Hong Kong and Mainland China. The total quantified carbonyl concentration, 37.9 +/- 9.3 microg/m3, was the highest at an entrance of a cross-harbor tunnel in downtown area. The theoretical carbonyls compositions of the three roadside locations were estimated according to the VE-dominated sample profiles and the statistics on vehicle numbers and types during the sampling period. The measured compositions of formaldehyde were much higher than the theoretical compositions in summer, demonstrating that photochemical reactions significantly contributed to the formaldehyde production in the roadsides. PMID:22442938

  15. Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice

    PubMed Central

    Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong

    2014-01-01

    Post-operative cognitive dysfunction (POCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain β-amyloid (Aβ) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The Aβ accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2α. γ-Secretase inhibitor compound E ameliorated the surgery-induced brain Aβ accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging- or Alzheimer gene mutation-associated Aβ accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD. PMID:24441878

  16. Age-dependent B cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis

    PubMed Central

    McLaughlin, Katherine A.; Chitnis, Tanuja; Newcombe, Jia; Franz, Bettina; Kennedy, Julia; McArdel, Shannon; Kuhle, Jens; Kappos, Ludwig; Rostasy, Kevin; Pohl, Daniela; Gagne, Donald; Ness, Jayne M.; Tenembaum, Silvia; O'Connor, Kevin C.; Viglietta, Vissia; Wong, Susan J.; Tavakoli, Norma P.; de Seze, Jerome; Khoury, Samia J.; Bar-Or, Amit; Hafler, David A.; Banwell, Brenda; Wucherpfennig, Kai W.

    2009-01-01

    Multiple sclerosis (MS) typically manifests in early to mid adulthood, but there is increasing recognition of pediatric-onset MS, aided by improvements in imaging techniques. The immunological mechanisms of disease are largely unexplored in pediatric-onset MS, in part because studies have historically focused on adult-onset disease. We investigated autoantibodies to myelin surface antigens in a large cohort of pediatric MS cases by flow cytometric labeling of transfectants that expressed different myelin proteins. While antibodies to native myelin oligodendrocyte glycoprotein (MOG) were uncommon among adult-onset patients, a subset of pediatric patients had serum antibodies that brightly labeled the MOG transfectant. Antibodies to two other myelin surface antigens were largely absent. Affinity purification of MOG antibodies as well as competition of binding with soluble MOG documented their binding specificity. The prevalence of such autoantibodies was highest among patients with a very early onset of MS: 38.7% of patients less than 10 years of age at disease onset had MOG antibodies, compared to 14.7% of patients in the 10–18 year age group. B cell autoimmunity to this myelin surface antigen is therefore most common in patients with a very early onset of MS. PMID:19687098

  17. Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice

    NASA Astrophysics Data System (ADS)

    Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong

    2014-01-01

    Post-operative cognitive dysfunction (POCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain β-amyloid (Aβ) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The Aβ accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2α. γ-Secretase inhibitor compound E ameliorated the surgery-induced brain Aβ accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging- or Alzheimer gene mutation-associated Aβ accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD.

  18. Age-dependent effects on social interaction of NMDA GluN2A receptor subtype-selective antagonism.

    PubMed

    Green, Torrian L; Burket, Jessica A; Deutsch, Stephen I

    2016-07-01

    NMDA receptor-mediated neurotransmission is implicated in the regulation of normal sociability in mice. The heterotetrameric NMDA receptor is composed of two obligatory GluN1 and either two "modulatory" GluN2A or GluN2B receptor subunits. GluN2A and GluN2B-containing receptors differ in terms of their developmental expression, distribution between synaptic and extrasynaptic locations, and channel kinetic properties, among other differences. Because age-dependent differences in disruptive effects of GluN2A and GluN2B subtype-selective antagonists on sociability and locomotor activity have been reported in rats, the current investigation explored age-dependent effects of PEAQX, a GluN2A subtype-selective antagonist, on sociability, stereotypic behaviors emerging during social interaction, and spatial working memory in 4- and 8-week old male Swiss Webster mice. The data implicate an age-dependent contribution of GluN2A-containing NMDA receptors to the regulation of normal social interaction in mice. Specifically, at a dose of PEAQX devoid of any effect on locomotor activity and mouse rotarod performance, the social interaction of 8-week old mice was disrupted without any effect on the social salience of a stimulus mouse. Moreover, PEAQX attenuated stereotypic behavior emerging during social interaction in 4- and 8-week old mice. However, PEAQX had no effect on spontaneous alternations, a measure of spatial working memory, suggesting that neural circuits mediating sociability and spatial working memory may be discrete and dissociable from each other. Also, the data suggest that the regulation of stereotypic behaviors and sociability may occur independently of each other. Because expression of GluN2A-containing NMDA receptors occurs at a later developmental stage, they may be more involved in mediating the pathogenesis of ASDs in patients with histories of "regression" after a period of normal development than GluN2B receptors.

  19. Predicting plasticity: acute context-dependent changes to vocal performance predict long-term age-dependent changes.

    PubMed

    James, Logan S; Sakata, Jon T

    2015-10-01

    Understanding the factors that predict and guide variation in behavioral change can lend insight into mechanisms of motor plasticity and individual differences in behavior. The performance of adult birdsong changes with age in a manner that is similar to rapid context-dependent changes to song. To reveal mechanisms of vocal plasticity, we analyzed the degree to which variation in the direction and magnitude of age-dependent changes to Bengalese finch song could be predicted by variation in context-dependent changes. Using a repeated-measures design, we found that variation in age-dependent changes to the timing, sequencing, and structure of vocal elements ("syllables") was significantly predicted by variation in context-dependent changes. In particular, the degree to which the duration of intersyllable gaps, syllable sequencing at branch points, and fundamental frequency of syllables within spontaneous [undirected (UD)] songs changed over time was correlated with the degree to which these features changed from UD song to female-directed (FD) song in young-adult finches (FDyoung). As such, the structure of some temporal features of UD songs converged over time onto the structure of FDyoung songs. This convergence suggested that the FDyoung song could serve as a stable target for vocal motor plasticity. Consequently, we analyzed the stability of FD song and found that the temporal structure of FD song changed significantly over time in a manner similar to UD song. Because FD song is considered a state of heightened performance, these data suggest that age-dependent changes could reflect practice-related improvements in vocal motor performance. PMID:26311186

  20. Increased age of transformed mouse neural progenitor/stem cells recapitulates age-dependent clinical features of human glioma malignancy

    PubMed Central

    Mikheev, Andrei M.; Ramakrishna, Rohan; Stoll, Elizabeth A.; Mikheeva, Svetlana A.; Beyer, Richard P.; Plotnik, David A.; Schwartz, Jeffrey L.; Rockhill, Jason K.; Silber, John R.; Born, Donald E.; Kosai, Yoshito; Horner, Philip J.; Rostomily, Robert C.

    2012-01-01

    Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3 and 18month old mice into 3 and 20-month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (p ≤ 0.0001) median survival in both 3month (37.5 vs 83 days) and 20-month (38 vs 67 days) hosts, indicating that age-dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF-1 promoter reporter activity and hypoxia response gene (HRG) expression, mirror the upregulation of HRGs in cohorts of older vs younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age-dependent differences in invasion, genomic instability and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age-dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas. PMID:22958206

  1. Leaf age dependent changes in within-canopy variation in leaf functional traits: a meta-analysis.

    PubMed

    Niinemets, Ülo

    2016-05-01

    Within-canopy variation in leaf structural and photosynthetic characteristics is a major means by which whole canopy photosynthesis is maximized at given total canopy nitrogen. As key acclimatory modifications, leaf nitrogen content (N A) and photosynthetic capacity (A A) per unit area increase with increasing light availability in the canopy and these increases are associated with increases in leaf dry mass per unit area (M A) and/or nitrogen content per dry mass and/or allocation. However, leaf functional characteristics change with increasing leaf age during leaf development and aging, but the importance of these alterations for within-canopy trait gradients is unknown. I conducted a meta-analysis based on 71 canopies that were sampled at different time periods or, in evergreens, included measurements for different-aged leaves to understand how within-canopy variations in leaf traits (trait plasticity) depend on leaf age. The analysis demonstrated that in evergreen woody species, M A and N A plasticity decreased with increasing leaf age, but the change in A A plasticity was less suggesting a certain re-acclimation of A A to altered light. In deciduous woody species, M A and N A gradients in flush-type species increased during leaf development and were almost invariable through the rest of the season, while in continuously leaf-forming species, the trait gradients increased constantly with increasing leaf age. In forbs, N A plasticity increased, while in grasses, N A plasticity decreased with increasing leaf age, reflecting life form differences in age-dependent changes in light availability and in nitrogen resorption for growth of generative organs. Although more work is needed to improve the coverage of age-dependent plasticity changes in some plant life forms, I argue that the age-dependent variation in trait plasticity uncovered in this study is large enough to warrant incorporation in simulations of canopy photosynthesis through the growing period.

  2. Predicting plasticity: acute context-dependent changes to vocal performance predict long-term age-dependent changes

    PubMed Central

    James, Logan S.

    2015-01-01

    Understanding the factors that predict and guide variation in behavioral change can lend insight into mechanisms of motor plasticity and individual differences in behavior. The performance of adult birdsong changes with age in a manner that is similar to rapid context-dependent changes to song. To reveal mechanisms of vocal plasticity, we analyzed the degree to which variation in the direction and magnitude of age-dependent changes to Bengalese finch song could be predicted by variation in context-dependent changes. Using a repeated-measures design, we found that variation in age-dependent changes to the timing, sequencing, and structure of vocal elements (“syllables”) was significantly predicted by variation in context-dependent changes. In particular, the degree to which the duration of intersyllable gaps, syllable sequencing at branch points, and fundamental frequency of syllables within spontaneous [undirected (UD)] songs changed over time was correlated with the degree to which these features changed from UD song to female-directed (FD) song in young-adult finches (FDyoung). As such, the structure of some temporal features of UD songs converged over time onto the structure of FDyoung songs. This convergence suggested that the FDyoung song could serve as a stable target for vocal motor plasticity. Consequently, we analyzed the stability of FD song and found that the temporal structure of FD song changed significantly over time in a manner similar to UD song. Because FD song is considered a state of heightened performance, these data suggest that age-dependent changes could reflect practice-related improvements in vocal motor performance. PMID:26311186

  3. Emissions of carbonyl compounds from various cookstoves in China

    SciTech Connect

    Zhang, J. . Environmental and Occupational Health Sciences Inst. East-West Center, Honolulu, HI ); Smith, K.R. Univ. of California, Berkeley, CA . Center for Occupational and Environmental Health)

    1999-07-15

    This paper presents a new database of carbonyl emission factors for commonly used cookstoves in China. The emission factors, reported both on a fuel-mass basis (mg/kg) and on a defined cooking-task basis (mg/task), were determined using a carbon balance approach for 22 types of fuel/stove combinations. These include various stoves using different species of crop residues and wood, kerosene, and several types of coals and gases. The results show that all the tested cookstoves produced formaldehyde and acetaldehyde and that the vast majority of the biomass stoves produced additional carbonyl compounds such as acetone, acrolein, propionaldehyde, crotonaldehyde, 2-butanone, isobutyraldehyde, butyraldehyde, isovaleraldehyde, valeraldehyde, hexaldehyde, benzaldehyde, o-tolualdehyde, m,p-tolualdehyde, and 2,4-dimethylbenzaldehyde. Carbonyls other than formaldehyde and acetaldehyde, however, were rarely generated by burning coal, coal gas, and natural gas. Kerosene and LPG stoves generated more carbonyl compounds than coal, coal gas, and natural gas stoves, but less than biomass stoves. Indoor levels of carbonyl compounds for typical village houses during cooking hours, estimated using a mass balance model and the measured emission factors, can be high enough to cause acute health effects documented for formaldehyde exposure, depending upon house parameters and individuals' susceptibility.

  4. Age-dependent increases in tau phosphorylation in the brains of type 2 diabetic rats correlate with a reduced expression of p62.

    PubMed

    Jung, Hyun-Jung; Kim, Yoon-Jeong; Eggert, Simone; Chung, Kwang Chul; Choi, Kyeong Sook; Park, Sun Ah

    2013-10-01

    Aging increases the co-incidence of Alzheimer's disease (AD) and type 2 diabetes (T2DM). However, the critical factors that contribute to the age-related increase in AD-T2DM comorbidity have yet to be clarified. In this study, aging effects and their relationship to AD-related pathology and T2DM as well as the underlying mechanisms of this process were investigated using obese rats with chronic T2DM. Tau pathology and its associated signaling pathways in the brain were compared between Otsuka Long-Evans Tokushima Fatty (OLETF) rats and corresponding non-diabetic controls at various ages. Tau phosphorylation at AD-related epitopes, including Thr212, Thr231, Ser262, and Ser396, increased with age in the soluble brain extracts of chronic OLETF rats and were accompanied by synaptic protein loss. There was also a marked age-dependent accumulation of polyubiquitinated substances in diabetic rats. Accordingly, tau proteins were highly polyubiquitinated in aged OLETF rats and a strong degree of co-localization existed between p-tau and ubiquitin in these neurons. In addition, the mRNA and protein levels of p62, a known cargo molecule that transports polyubiquitinated tau to proteasomal and autophagic degradation systems, decreased robustly with age in OLETF rats and there was an inverse correlation between protein levels of p62 and p-tau. The impaired degradation of polyubiquitinated p-tau due to age- and T2DM-dependent decreases in p62 transcription is a primary mechanism underlying increased AD-like pathology in a T2DM rat model as age increases. These results provide novel insight into the mechanisms supporting the age-related increase in AD-T2DM comorbidity.

  5. Reactive Carbonyl Species Derived from Omega-3 and Omega-6 Fatty Acids.

    PubMed

    Wang, Yu; Cui, Ping

    2015-07-22

    Inflammation-related reactive oxygen species (ROS) and reactive nitrogen species (RNS) are associated with the development of cancer. ROS and RNS can directly damage biomacromolecules such as proteins, DNA, and lipids. Lipid peroxidation, however, can result in reactive carbonyl species (RCS) that can also modify proteins and DNA. In contrast to an extensive literature on the modification of proteins and DNA from omega-6 fatty acids, there are few studies on RCS generation from other fatty acids, particularly omega-3 fatty acids, which are frequently consumed from the diet and diet supplements. Therefore, a comparison between omega-3 and omega-6 fatty acids has been conducted. LC-MS/MS analysis of carbonyl-dinitrophenylhydrazine (DNPH) standards yielded characteristic fragment ions. Autoxidation products of α-linolenic acid and linoleic acid were then derivatized with DNPH and analyzed by LC-MS/MS. The results showed that α-linolenic acid, an omega-3 fatty acid, generated more acrolein and crotonaldehyde than did linoleic acid, an omega-6 fatty acid. Omega-3 fatty acids might be easily degraded to smaller monoaldehydes or dicarbonyls. Omega-3 fatty acids have been considered as health improvement components for a long time. However, on the basis of the results presented here, use of omega-3 fatty acids should be re-evaluated in vivo for safety purposes.

  6. Temperature dependence of fast carbonyl backbone dynamics in chicken villin headpiece subdomain.

    PubMed

    Vugmeyster, Liliya; Ostrovsky, Dmitry

    2011-06-01

    Temperature-dependence of protein dynamics can provide information on details of the free energy landscape by probing the characteristics of the potential responsible for the fluctuations. We have investigated the temperature-dependence of picosecond to nanosecond backbone dynamics at carbonyl carbon sites in chicken villin headpiece subdomain protein using a combination of three NMR relaxation rates: (13)C' longitudinal rate, and two cross-correlated rates involving dipolar and chemical shift anisotropy (CSA) relaxation mechanisms, (13)C'/(13)C'-(13)C(α) CSA/dipolar and (13)C'/(13)C'-(15)N CSA/dipolar. Order parameters have been extracted using the Lipari-Szabo model-free approach assuming a separation of the time scales of internal and molecular motions in the 2-16°C temperature range. There is a gradual deviation from this assumption from lower to higher temperatures, such that above 16°C the separation of the time scales is inconsistent with the experimental data and, thus, the Lipari-Szabo formalism can not be applied. While there are variations among the residues, on the average the order parameters indicate a markedly steeper temperature dependence at backbone carbonyl carbons compared to that probed at amide nitrogens in an earlier study. This strongly advocates for probing sites other than amide nitrogen for accurate characterization of the potential and other thermodynamics characteristics of protein backbone.

  7. Electron and bromine transfer reactions between metal carbonyl anions and metal carbonyl bromides. Crystal and molecular structure of dimeric indenyl molybdenum tricarbonyl

    SciTech Connect

    Striejewske, W.S.; See, R.F.; Churchill, M.R.; Atwood, J.D. )

    1993-11-01

    Reactions of metal carbonyl anions with metal carbonyl halides proceed by two separate paths. When the reactant anion is a strong nucleophile, the halogen is transferred, resulting in a new metal carbonyl halide and a new metal carbonyl anion as intermediates. The ultimate products, in this case, are the homobimetallic complexes. In cases where the reactant metal carbonyl anion is a poor nucleophile, a single electron transfer occurs, leading to the two homobimetallic complexes and to the heterobimetallic complex. Halide effects and possible indenyl effects are examined. The complex [Mo(indenyl)(CO)[sub 3

  8. Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment

    PubMed Central

    LeBlanc, A C; Ramcharitar, J; Afonso, V; Hamel, E; Bennett, D A; Pakavathkumar, P; Albrecht, S

    2014-01-01

    Active Caspase-6 is abundant in the neuropil threads, neuritic plaques and neurofibrillary tangles of Alzheimer disease brains. However, its contribution to the pathophysiology of Alzheimer disease is unclear. Here, we show that higher levels of Caspase-6 activity in the CA1 region of aged human hippocampi correlate with lower cognitive performance. To determine whether Caspase-6 activity, in the absence of plaques and tangles, is sufficient to cause memory deficits, we generated a transgenic knock-in mouse that expresses a self-activated form of human Caspase-6 in the CA1. This Caspase-6 mouse develops age-dependent spatial and episodic memory impairment. Caspase-6 induces neuronal degeneration and inflammation. We conclude that Caspase-6 activation in mouse CA1 neurons is sufficient to induce neuronal degeneration and age-dependent memory impairment. These results indicate that Caspase-6 activity in CA1 could be responsible for the lower cognitive performance of aged humans. Consequently, preventing or inhibiting Caspase-6 activity in the aged may provide an efficient novel therapeutic approach against Alzheimer disease. PMID:24413155

  9. Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

    PubMed

    Babenko, Nataliya A; Garkavenko, Vladimir V; Storozhenko, Galina V; Timofiychuk, Olga A

    2016-04-01

    Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID:26830134

  10. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    PubMed

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

  11. Age-dependent decline in learning and memory performances of WAG/Rij rat model of absence epilepsy

    PubMed Central

    2012-01-01

    Recent clinical studies revealed emotional and cognitive impairments associated with absence epilepsy. Preclinical research with genetic models of absence epilepsy however have primarily focused on dysfunctional emotional processes and paid relatively less attention to cognitive impairment. In order to bridge this gap, we investigated age-dependent changes in learning and memory performance, anxiety-like behavior, and locomotor activity of WAG/Rij rats (a valid model of generalized absence epilepsy) using passive avoidance, Morris water maze, elevated plus maze, and locomotor activity cage. We tested 5 month-old and 13 month-old WAG/Rij rats and compared their performance to age-matched Wistar rats. Results revealed a decline in emotional and spatial memory of WAG/Rij rats compared to age-matched Wistar rats only at 13 months of age. Importantly, there were no significant differences between WAG/Rij and Wistar rats in terms of anxiety-like behavior and locomotor activity at either age. Results pointed at age-dependent learning and memory deficits in the WAG/Rij rat model of absence epilepsy. PMID:22998946

  12. Age-dependent development of the splenic marginal zone in human infants is associated with different causes of death.

    PubMed

    Kruschinski, Carsten; Zidan, Mohamed; Debertin, Anette S; von Hörsten, Stephan; Pabst, Reinhard

    2004-01-01

    Infants are more susceptible to infections caused by T cell- independent type 2 (TI-2) polysaccharide antigens of certain encapsulated bacteria. Immune responses against this type of antigen are related to the splenic marginal zone (MZ). However, only few data exist on the age-dependent developmental stages of the human spleen in early childhood and on their association with different diseases. Therefore, the present study aimed to investigate spleens of a large number of children at very young ages (12 days to 32 months), derived from autopsy cases. Immunohistochemical labeling was performed on paraffin sections of 34 spleens using a panel of monoclonal antibodies. The shape and size of the white pulp compartments were examined and correlated to the cause of death of the children. Results show that the development of the different compartments was statistically age-dependent, but no clear-cut time point for the maturity of each compartment was seen. Furthermore, the MZ was significantly more often missing when sudden infant death (SID) and/or infection were the cause of death, compared with other violent or traumatic reasons that served as controls. This association supports the concept that an immature state of the spleen and especially of the MZ might contribute to the increased susceptibility to bacterial infections in young infants.

  13. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences.

    PubMed

    Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

    2015-03-01

    NAD is an essential metabolite that exists in NAD(+) or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD(+)/NADH redox state and modulating cellular signaling processes through the activity of the NAD(+)-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD(+) and NADH contents and the NAD(+)/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.

  14. Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus.

    PubMed

    Chakraborty, Goutam; Thumpayil, Sherin; Lafontant, David-Erick; Woubneh, Wolde; Toney, Jeffrey H

    2009-11-01

    Yellow KK mice carrying the 'yellow obese' gene Ay are a well established polygenic model for human non-insulin dependent diabetes mellitus. These animals develop marked adiposity and decreased glucose tolerance relative to their control littermates, KK mice. The authors monitored glucose tolerance in KK-Ay mice over time and observed a significant (Page-dependent improvement (13.3% by 175 d of age and 36.4% by 212 d of age, relative to 85 d of age). During the same time period, body weight and food and water consumption were relatively constant. The authors also measured plasma levels of endocrine hormones that are important in diabetes. Levels of insulin were approximately 8 times higher and levels of amylin 3 times higher in 220-d-old KK-Ay mice than in 180-d-old mice, whereas levels of glucagon-like peptide 1, glucagon and leptin remained relatively constant. These findings suggest that KK-Ay mice undergo an age-dependent improvement of glucose tolerance when maintained on a normal diet for 25 weeks or longer, due in part to increases in plasma levels of insulin and amylin.

  15. Catalytic production of metal carbonyls from metal oxides

    DOEpatents

    Sapienza, R.S.; Slegeir, W.A.; Foran, M.T.

    1984-01-06

    This invention relates to the formation of metal carbonyls from metal oxides and specially the formation of molybdenum carbonyl and iron carbonyl from their respective oxides. Copper is used here in admixed form or used in chemically combined form as copper molybdate. The copper/metal oxide combination or combined copper is utilized with a solvent, such as toluene and subjected to carbon monoxide pressure of 25 atmospheres or greater at about 150 to 260/sup 0/C. The reducing metal copper is employed in catalytic concentrations or combined concentrations as CuMoO/sub 4/ and both hydrogen and water present serve as promoters. It has been found that the yields by this process have been salutary and that additionally the catalytic metal may be reused in the process to good effect. 3 tables.

  16. Catalytic production of metal carbonyls from metal oxides

    DOEpatents

    Sapienza, Richard S.; Slegeir, William A.; Foran, Michael T.

    1984-01-01

    This invention relates to the formation of metal carbonyls from metal oxides and specially the formation of molybdenum carbonyl and iron carbonyl from their respective oxides. Copper is used here in admixed form or used in chemically combined form as copper molybdate. The copper/metal oxide combination or combined copper is utilized with a solvent, such as toluene and subjected to carbon monoxide pressure of 25 atmospheres or greater at about 150.degree.-260.degree. C. The reducing metal copper is employed in catalytic concentrations or combined concentrations as CuMoO.sub.4 and both hydrogen and water present serve as promoters. It has been found that the yields by this process have been salutary and that additionally the catalytic metal may be reused in the process to good effect.

  17. Comparison of antimicrobial properties of monoterpenes and their carbonylated products.

    PubMed

    Naigre, R; Kalck, P; Roques, C; Roux, I; Michel, G

    1996-06-01

    Some monoterpenes and their carbonylated products were evaluated for their antibacterial and antifungal properties. The carbonylation of tested monoterpenes was shown to increase the bacteriostatic and fungistatic activities specifically by the contact method. Concerning the killing effects, only (1R,2S,5R)-isopulegol, its carbonylated products, and (R)-carvone showed significant bactericidal activities, particularly against Enterococcus faecium and Escherichia coli above a concentration of 10 microliters/ml. A fungicidal efficiency of (1R,2S,5R)-isopulegol and (R)-carvone against Aspergillus niger was also noted. It seems that the presence of an oxygenated function in the framework increases the antimicrobial properties. However, monoterpenes were more active using a micro-atmosphere method. PMID:8693045

  18. Hydrocarboxylation of olefins in presence of carbonyl forms of cobalt

    SciTech Connect

    Gvozdovskii, G.N.; Gavrilova, V.M.; Rybakov, V.A.; Blanshtein, I.B.

    1987-09-10

    The increasing shortage of plant and animal fats for the production of the higher carboxylic acids has necessitated the development of methods for the production of these acids from petroleum. This paper studies the hydrocarboxylation of petroleum olefins in the presence of cobalt carbonyls and the effect of three promoters--pyridine, acetone, and cyclohexanone--on the hydrolysis rate and catalytic behavior of the carbonyls and the subsequent rate of hydrocarboxylation of the olefines. Ethylene is used as the sample olefin. The role of water in the reactions is also assessed.

  19. Magnetorheological Fluids with Carbonyl and Water Atomized Iron Powders

    NASA Astrophysics Data System (ADS)

    Bombard, Antonio J. F.; Teodoro, João Victor R.

    Our aim in this work was to propose the use of a ternary blend of two carbonyl iron powder CIP, mixed with water atomized iron powder (WAIP), to reduce the off-state viscosity, without prejudice of MRF performance in terms of yield stress and torque output. The idea of mix water atomized iron powder with carbonyl iron powder is not new. The US Pat. # 5,900,184 by Weiss et al. (1999) describes that a binary blend, half-to-half, can reduces the viscosity of MRF in the absence of magnetic field, and increase the torque output under field.

  20. Age-dependent changes in lipid peroxide levels in peripheral organs, but not in brain, in senescence-accelerated mice.

    PubMed

    Matsugo, S; Kitagawa, T; Minami, S; Esashi, Y; Oomura, Y; Tokumaru, S; Kojo, S; Matsushima, K; Sasaki, K

    2000-01-01

    The tissue concentration of lipid peroxides was determined in the brain, heart, liver, lung and kidney of accelerated senescence-prone (SAMP-8) and -resistant (SAMR-1) mice at 3, 6 and 9 months of age by a method involving chemical derivatization and high performance liquid chromatography. The level of lipid peroxides in the brain did not show an age-dependent change, but at each age the brain level of lipid peroxides was significantly higher in SAMP-8 than in SAMR-1. In contrast, the lipid peroxide levels in the peripheral organs showed increases with aging in both strains, and they were significantly higher in SAMP-8 than in SAMR-1 at both 3 and 6 months of age (except at 3 months of age in the kidney). These results suggest that increased oxidative stress in the brain and peripheral organs is a cause of the senescence-related degeneration and impairments seen in SAMP-8. PMID:10643812

  1. The structure of optimal time- and age-dependent harvesting in the Lotka-McKendrik population model.

    PubMed

    Hritonenko, Natali; Yatsenko, Yuri

    2007-07-01

    The paper analyzes optimal harvesting of age-structured populations described by the Lotka-McKendrik model. It is shown that the optimal time- and age-dependent harvesting control involves only one age at natural conditions. This result leads to a new optimization problem with the time-dependent harvesting age as an unknown control. The integral Lotka model is employed to explicitly describe the time-varying age of harvesting. It is proven that in the case of the exponential discounting and infinite horizon the optimal strategy is a stationary solution with a constant harvesting age. A numeric example on optimal forest management illustrates the theoretical findings. Discussion and interpretation of the results are provided.

  2. [ROLE OF NEUTRAL SPHINGOMYELINASE IN AGE-DEPENDENT MUSCLE INSULIN RESISTANCE DEVELOPMENT AND ITS IMPROVEMENT WITH N-ACETYLCYSTEINE].

    PubMed

    Babenko, N A; Timofiĭchuk, O A; Belyĭ, A N

    2015-01-01

    In the present study, we evaluated the role of ceramide in age-dependent and etoposide-induced insulin resistance. A significant increase in the level of ceramide and decrease of gluthatione (GSH) content and tissue sensitivity to insulin has been observed in 24-month-old rats as compared with 3-month-old animals. Etoposide imitates ageing-like changes in muscle tissue of young rats. N-acetylcysteine as well as specific neutral sphingomyelinase (nSMase) inhibitor--GW4869, decreases ceramide content and increases GSH level, and enhances the insulin-induced [3H-D-glucose uptake in the "aged" tissue. These data indicate that nSMase play important role in the age- and drug-induced ceramide-dependent insuline resistance. PMID:26390620

  3. Age-dependent susceptibilities of Bulinus truncatus snails to an aqueous extract of Pulicaria crispa (Forssk.) Oliv. (Asteraceae) leaves.

    PubMed

    Ali, Elnour A; Bushara, Hamid O; Ali, Faisal S; Hussein, Mansour F

    2009-05-01

    This study was carried out to investigate the potential use of the herb Pulicaria crispa in the biological control of different developmental stages of Bulinus truncatus, a major snail intermediate host of urinary schistosomiasis. Age-dependent susceptibilities of mature adult snails, immature snails, juveniles, and one-day old egg masses to aqueous extracts of Pulicaria crispa leaves collected from Khartoum (Sudan) and Riyadh (Saudi Arabia) was determined and compared. The results show the juvenile snails are the most susceptible, followed in descending order by one-day old egg masses, immature snails, and mature adult snails. The P. crispa sample collected from Riyadh was significantly more potent against B. truncatus than that collected from Khartoum, as indicated by the least (LC50) and (LC90) values for all B. truncatus ages.

  4. Functional aging in the nervous system contributes to age-dependent motor activity decline in C. elegans.

    PubMed

    Liu, Jie; Zhang, Bi; Lei, Haoyun; Feng, Zhaoyang; Liu, Jianfeng; Hsu, Ao-Lin; Xu, X Z Shawn

    2013-09-01

    Aging is characterized by a progressive decline in multiple physiological functions (i.e., functional aging). As animals age, they exhibit a gradual loss in motor activity, but the underlying mechanisms remain unclear. Here we approach this question in C. elegans by functionally characterizing its aging nervous system and muscles. We find that motor neurons exhibit a progressive functional decline, beginning in early life. Surprisingly, body-wall muscles, which were previously thought to undergo functional aging, do not manifest such a decline until mid-late life. Notably, motor neurons first develop a deficit in synaptic vesicle fusion followed by that in quantal size and vesicle docking/priming, revealing specific functional deteriorations in synaptic transmission. Pharmacological stimulation of synaptic transmission can improve motor activity in aged animals. These results uncover a critical role for the nervous system in age-dependent motor activity decline in C. elegans and provide insights into how functional aging occurs in this organism.

  5. TIEG1-null tenocytes display age-dependent differences in their gene expression, adhesion, spreading and proliferation properties

    SciTech Connect

    Haddad, Oualid; Gumez, Laurie; Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Bensamoun, Sabine F.

    2011-07-15

    The remodeling of extracellular matrix is a crucial mechanism in tendon development and the proliferation of fibroblasts is a key factor in this process. The purpose of this study was to further elucidate the role of TIEG1 in mediating important tenocyte properties throughout the aging process. Wildtype and TIEG1 knockout tenocytes adhesion, spreading and proliferation were characterized on different substrates (fibronectin, collagen type I, gelatin and laminin) and the expression levels of various genes known to be involved with tendon development were analyzed by RT-PCR. The experiments revealed age-dependent and substrate-dependent properties for both wildtype and TIEG1 knockout tenocytes. Taken together, our results indicate an important role for TIEG1 in regulating tenocytes adhesion, spreading, and proliferation throughout the aging process. Understanding the basic mechanisms of TIEG1 in tenocytes may provide valuable information for treating multiple tendon disorders.

  6. Age-dependent HLA profiles of the Israeli population: impact on hematopoietic cell donor recruitment and availability.

    PubMed

    Israeli, Moshe; Oudshoorn, Machteld; Haasnoot, Geert W; Klein, Tirza; Zisser, Bracha; Bach, Gideon; Claas, Frans H J

    2014-10-01

    Approximately three million people have immigrated to the state of Israel since it was founded. Consequently, the immunogenetic profile of the younger generation may consist of a genetic mixture of formerly distinct population groups. We aimed to investigate whether HLA profiles in the Israeli population are age dependent and how this influences representation of various age groups in local donor registries. We determined HLA-A*, HLA-B*, and HLA-DRB1* low-resolution phenotypes of three age groups (n = 4,169 in each): (1) cord blood units collected between 2009 and 2013 (BABIES) and adult registry donors (2) aged 18-28 years (YOUNG) and (3) aged 49-60 years (OLD). We compared the results with virtual groups that simulate the offspring of the actual study groups. None of the three actual age groups were in Hardy-Weinberg equilibrium. The YOUNG presented four HLA-B alleles that were absent in the OLD and BABIES. A significantly higher percentage among the OLD and BABIES had a "matched" individual within their group in comparison to the YOUNG. In the YOUNG, the 10 most common haplotypes account for 16.7 % of the population, in comparison to 18.2 % in the OLD or 19.8 % in the BABIES group. The BABIES group was genetically remote from all other groups. Further disparities were found between the actual and the corresponding virtual groups. We conclude that discrete age groups in Israel present distinct immunogenetic profiles, where the younger generation is more heterogeneous. The population dynamics of the age-dependent HLA profile is multifactorial: gradual intersubgroup admixture, nonrandom mating, and entry of new alleles.

  7. Cell cycle age dependence for radiation-induced G/sub 2/ arrest: evidence for time-dependent repair

    SciTech Connect

    Rowley, R.

    1985-09-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G/sub 2/. The sensitivity of Chinese hamster ovary cells to G/sub 2/ arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G/sub 2/. This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G/sub 2/ arrest and/or by changes in capability for postirradiation recovery from G/sub 2/ arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G/sub 2/ arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G/sub 2/ arrest, while inhibiting repair of G/sub 2/ arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G/sub 2/ arrest was expressed. The duration of G/sub 2/ arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G/sub 2/ arrest induction is present throughout the cell cycle and that the level of G/sub 2/ arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G/sub 2/ arrest.

  8. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    SciTech Connect

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  9. Age-dependent microRNA control of synaptic plasticity in 22q11 deletion syndrome and schizophrenia

    PubMed Central

    Earls, Laurie R.; Fricke, R. Gaines; Yu, Jing; Berry, Raymond B.; Baldwin, Lisa T.; Zakharenko, Stanislav S.

    2012-01-01

    The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5–3Mb region of chromosome 22. 22q11DS constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2), which is responsible for loading Ca2+ into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca2+ load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency of Dgcr8, a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP in Dgcr8+/− mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia. PMID:23055483

  10. Inverse U-shaped curve for age dependency of torsional eye movement responses to galvanic vestibular stimulation.

    PubMed

    Jahn, Klaus; Naessl, Andrea; Schneider, Erich; Strupp, Michael; Brandt, Thomas; Dieterich, Marianne

    2003-07-01

    To investigate age dependent changes we analysed torsional eye movement responses to binaural and monaural galvanic vestibular stimulation (GVS) in 57 healthy subjects (20-69 years old). GVS (1-3 mA) induced torsional eye movements consisting of static torsion toward the anode (amplitude 1-6 degrees ) and superimposed torsional nystagmus (slow phase velocity 0.5-3 degrees /s, quick phase amplitude 0.5-2 degrees, nystagmus frequency 0.75-1.5 s-1). Static ocular torsion and torsional nystagmus increased from the third to the sixth decade and decreased in older subjects, e.g. slow phase velocity increased from 1.5 degrees /s (20-29 years) to 2.9 degrees /s (50-59 years) and decreased to 2.5 degrees /s for the seventh decade (60-69 years). Thus, an inverse U-shaped curve was found for the dependence of torsional eye movement responses on age. All structures relevant for vestibular function degenerate with age, but at varying times. Since hair cell loss precedes those seen in the vestibular nerve and Scarpa's ganglion, the decrease in hair cell counts could be compensated for by increased sensitivity of afferent nerve fibres or central mechanisms. Increased sensitivity could thus maintain normal function despite reduced peripheral input. As GVS acts at the vestibular nerve (thereby bypassing the hair cells), electrical stimulation should be more efficient in subjects with the beginning of hair cell degeneration, as seen in our data up to the sixth decade. The degeneration of nerve fibres, ganglion cells and central neurons becomes evident at older ages. Thus, the compensatory increase in sensitivity breaks down and GVS-induced eye movements decline-a finding that is reflected by the inverse U-shaped curve for age dependency presented in this study.

  11. Carbonyl atmospheric reaction products of aromatic hydrocarbons in ambient air

    NASA Astrophysics Data System (ADS)

    Obermeyer, Genevieve; Aschmann, Sara M.; Atkinson, Roger; Arey, Janet

    To convert gaseous carbonyls to oximes during sampling, an XAD-4 resin denuder system pre-coated with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine and followed by analysis with methane positive chemical ionization gas chromatography/mass spectrometry was used to measure carbonyls in ambient air samples in Riverside, CA. In conjunction with similar analyses of environmental chamber OH radical-initiated reactions of o- and p-xylene, 1,2,4-trimethylbenzene, ethylbenzene, 4-hydroxy-2-butanone and 1,4-butanediol, we identified benzaldehyde, o-, m- and p-tolualdehyde and acetophenone and the dicarbonyls glyoxal, methylglyoxal, biacetyl, ethylglyoxal, 1,4-butenedial, 3-hexene-2,5-dione, 3-oxo-butanal, 1,4-butanedial and malonaldehyde in the ambient air samples. As discussed, these carbonyls and dicarbonyls can be formed from the OH radical-initiated reactions of aromatic hydrocarbons and other volatile organic compounds emitted into the atmosphere, and we conclude that in situ atmospheric formation is a major source of these carbonyls in our Riverside, CA, ambient air samples.

  12. Metal-Diazo Radicals of α-Carbonyl Diazomethanes.

    PubMed

    Li, Feifei; Xiao, Longqiang; Liu, Lijian

    2016-01-01

    Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [Rh(I)Cl(cod)]2, [Co(II)(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [Rh(I)Cl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N∙ (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C∙, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C∙, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals. PMID:26960916

  13. CARBONYLATION OF MYOSIN HEAVY CHAINS IN RAT HEARTS DURING DIABETES

    PubMed Central

    Shao, Chun-Hong; Rozanski, George J.; Nagai, Ryoji; Stockdale, Frank E.; Patel, Kaushik P.; Wang, Mu; Singh, Jaipaul; Mayhan, William G.; Bidasee, Keshore R.

    2010-01-01

    Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for six weeks, while the other group received no treatment. After eight weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca2+- and Mg2+-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-α to MHC-β ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-α and MHC-β. Aminoguandine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca2+-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes. PMID:20359464

  14. Carbonylation of myosin heavy chains in rat heart during diabetes.

    PubMed

    Shao, Chun-Hong; Rozanski, George J; Nagai, Ryoji; Stockdale, Frank E; Patel, Kaushik P; Wang, Mu; Singh, Jaipaul; Mayhan, William G; Bidasee, Keshore R

    2010-07-15

    Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later the animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for 6 weeks, while the other group received no treatment. After 8 weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca(2+)- and Mg(2+)-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-alpha to MHC-beta ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-alpha and MHC-beta. Aminoguanidine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca(2+)-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes.

  15. Iron-Sulfur-Carbonyl and -Nitrosyl Complexes: A Laboratory Experiment.

    ERIC Educational Resources Information Center

    Glidewell, Christopher; And Others

    1985-01-01

    Background information, materials needed, procedures used, and typical results obtained, are provided for an experiment on iron-sulfur-carbonyl and -nitrosyl complexes. The experiment involved (1) use of inert atmospheric techniques and thin-layer and flexible-column chromatography and (2) interpretation of infrared, hydrogen and carbon-13 nuclear…

  16. Methyl substituted polyimides containing carbonyl and ether connecting groups

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Havens, Stephen J. (Inventor)

    1992-01-01

    Polyimides were prepared from the reaction of aromatic dianhydrides with novel aromatic diamines having carbonyl and ether groups connecting aromatic rings containing pendant methyl groups. The methyl substituent polyimides exhibit good solubility and form tough, strong films. Upon exposure to ultraviolet irradiation and/or heat, the methyl substituted polyimides crosslink to become insoluble.

  17. Cobalt carbonyl catalyzed olefin hydroformylation in supercritical carbon dioxide

    DOEpatents

    Rathke, J.W.; Klingler, R.J.

    1993-03-30

    A method of olefin hydroformylation is provided wherein an olefin reacts with a carbonyl catalyst and with reaction gases such as hydrogen and carbon monoxide in the presence of a supercritical reaction solvent, such as carbon dioxide. The invention provides higher yields of n-isomer product without the gas-liquid mixing rate limitation seen in conventional Oxo processes using liquid media.

  18. Cobalt carbonyl catalyzed olefin hydroformylation in supercritical carbon dioxide

    DOEpatents

    Rathke, Jerome W.; Klingler, Robert J.

    1993-01-01

    A method of olefin hydroformylation is provided wherein an olefin reacts with a carbonyl catalyst and with reaction gases such as hydrogen and carbon monoxide in the presence of a supercritical reaction solvent, such as carbon dioxide. The invention provides higher yields of n-isomer product without the gas-liquid mixing rate limitation seen in conventional Oxo processes using liquid media.

  19. Comparing Carbonyl Chemistry in Comprehensive Introductory Organic Chemistry Textbooks

    ERIC Educational Resources Information Center

    Nelson, Donna J.; Kumar, Ravi; Ramasamy, Saravanan

    2015-01-01

    Learning the chemistry of compounds containing carbonyl groups is difficult for undergraduate students partly because of a convolution of multiple possible reaction sites, competitive reactions taking place at those sites, different criteria needed to discern between the mechanisms of these reactions, and no straightforward selection method…

  20. Metal-Diazo Radicals of α-Carbonyl Diazomethanes

    PubMed Central

    Li, Feifei; Xiao, Longqiang; Liu, Lijian

    2016-01-01

    Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [RhICl(cod)]2, [CoII(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [RhICl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N∙ (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C∙, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C∙, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals. PMID:26960916

  1. Metal-Diazo Radicals of α-Carbonyl Diazomethanes

    NASA Astrophysics Data System (ADS)

    Li, Feifei; Xiao, Longqiang; Liu, Lijian

    2016-03-01

    Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [RhICl(cod)]2, [CoII(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [RhICl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N• (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C•, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C•, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals.

  2. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS...

  3. Oral treatment with the herbal formula B401 protects against aging-dependent neurodegeneration by attenuating oxidative stress and apoptosis in the brain of R6/2 mice

    PubMed Central

    Wang, Sheue-Er; Lin, Ching-Lung; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Background Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington’s disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice. Objective To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients. Methods The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques. Results R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue. Conclusion Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration. PMID:26609226

  4. A correlation of reactive oxygen species accumulation by depletion of superoxide dismutases with age-dependent impairment in the nervous system and muscles of Drosophila adults.

    PubMed

    Oka, Saori; Hirai, Jun; Yasukawa, Takashi; Nakahara, Yasuyuki; Inoue, Yoshihiro H

    2015-08-01

    The theory that accumulation of reactive oxygen species (ROS) in internal organs is a major promoter of aging has been considered negatively. However, it is still controversial whether overexpression of superoxide dismutases (SODs), which remove ROS, extends the lifespan in Drosophila adults. We examined whether ROS accumulation by depletion of Cu/Zn-SOD (SOD1) or Mn-SOD (SOD2) influenced age-related impairment of the nervous system and muscles in Drosophila. We confirmed the efficient depletion of Sod1 and Sod2 through RNAi and ROS accumulation by monitoring of ROS-inducible gene expression. Both RNAi flies displayed accelerated impairment of locomotor activity with age and shortened lifespan. Similarly, adults with nervous system-specific depletion of Sod1 or Sod2 also showed reduced lifespan. We then found an accelerated loss of dopaminergic neurons in the flies with suppressed SOD expression. A half-dose reduction of three pro-apoptotic genes resulted in a significant suppression of the neuronal loss, suggesting that apoptosis was involved in the neuronal loss caused by SOD silencing. In addition, depletion of Sod1 or Sod2 in musculature is also associated with enhancement of age-related locomotion impairment. In indirect flight muscles from SOD-depleted adults, abnormal protein aggregates containing poly-ubiquitin accumulated at an early adult stage and continued to increase as the flies aged. Most of these protein aggregates were observed between myofibril layers. Moreover, immuno-electron microscopy indicated that the aggregates were predominantly localized in damaged mitochondria. These findings suggest that muscular and neuronal ROS accumulation may have a significant effect on age-dependent impairment of the Drosophila adults.

  5. 40 CFR 721.10409 - Poly(oxyalkylenediyl), .alpha. - [ [ [methyl - 3 - [ [ [ (polyfluoroalkyl)oxy]carbonyl ] amino...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Poly(oxyalkylenediyl), .alpha... Poly(oxyalkylenediyl), .alpha. - carbonyl ] amino] phenyl]amino]carbonyl] - .omega. - methoxy... identified generically as poly(oxyalkylenediyl), .alpha.- carbonyl]amino]phenyl]amino]...

  6. Measuring Electrostatic Fields in Both Hydrogen Bonding and non-Hydrogen Bonding Environments using Carbonyl Vibrational Probes

    PubMed Central

    Fried, Stephen D.; Bagchi, Sayan; Boxer, Steven G.

    2013-01-01

    Vibrational probes can provide a direct read-out of the local electrostatic field in complex molecular environments, such as protein binding sites and enzyme active sites. This information provides an experimental method to explore the underlying physical causes of important biomolecular processes such as binding and catalysis. However, specific chemical interactions such as hydrogen bonds can have complicated effects on vibrational probes and confound simple electrostatic interpretations of their frequency shifts. We employ vibrational Stark spectroscopy along with infrared spectroscopy of carbonyl probes in different solvent environments and in Ribonuclease S to understand the sensitivity of carbonyl frequencies to electrostatic fields, including those due to hydrogen bonds. Additionally, we carried out molecular dynamics simulations to calculate ensemble-averaged electric fields in solvents and in Ribonuclease S, and found excellent correlation between calculated fields and vibrational frequencies. These data enabled the construction of a robust field-frequency calibration curve for the C=O vibration. The present results suggest that carbonyl probes are capable of quantitatively assessing the electrostatics of hydrogen bonding, making them promising for future study of protein function. PMID:23808481

  7. Free backbone carbonyls mediate rhodopsin activation.

    PubMed

    Kimata, Naoki; Pope, Andreyah; Sanchez-Reyes, Omar B; Eilers, Markus; Opefi, Chikwado A; Ziliox, Martine; Reeves, Philip J; Smith, Steven O

    2016-08-01

    Conserved prolines in the transmembrane helices of G-protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilization of the receptor structure. To address the role of conserved prolines in family A GPCRs through solid-state NMR spectroscopy, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily. The free backbone C=O groups on helices H5 and H7 stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released, thus facilitating repacking of H5 and H7 onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles of prolines in membrane proteins. PMID:27376589

  8. Properties of M31 . I. Dust. Basic properties and a discussion about age-dependent dust heating

    NASA Astrophysics Data System (ADS)

    Montalto, M.; Seitz, S.; Riffeser, A.; Hopp, U.; Lee, C.-H.; Schönrich, R.

    2009-11-01

    Aims: Observations acquired by the Spitzer Space Telescope and improvements to theoretical modeling of dust emission properties are used to discuss the distribution of dust and its characteristics in the closest neighbor spiral galaxy M31. These data are then used with GALEX FUV, NUV, and SDSS images to study the age dependence of the dust heating process. Methods: Spitzer IRAC/MIPS maps of M31 were matched together and compared to dust emission models allowing us to constrain the dust mass, the intensity of the mean radiation field, the abundance of polycyclic aromatic hydrocarbon (PAH) particles. The total infrared emission (TIR) was analyzed as a function of UV and optical colors and compared to predictions of models that consider age-dependent dust heating. Results: We demonstrate that cold-dust component emission dominates the infrared spectral energy distribution of M31. The mean intensity of the radiation field heating the dust is low (typically U < 2, where U = 1 is the value in the solar neighborhood). Because of a lack of submillimeter observations, the dust mass (M_dust) is only weakly constrained by the infrared spectrum, but we derived a lower limit of M_dust ≳ 1.1 × 107 M⊙ with a best-fit model value of M_dust = 7.6 × 107 M⊙, in good agreement with expectations from CO and HI measurements. Across the spiral-ring structure of M31, we show that a fraction >3% of the total dust mass is in PAHs. UV and optical colors are correlated with the total infrared to far ultraviolet (TIR/FUV) ratios in ~670 pc-sized regions over the disk of M31, although deviating from the relationship between infrared excess and ultraviolet spectral slope (referred as IRX-β relationship) for starburst galaxies. In particular, redder regions have lower values of the TIR/FUV ratio for a fixed color. Considering the predictions of models that account for the dust-heating age dependence, we found that in 83% of the regions analyzed across the 10 kpc ring, more than 50% of

  9. Shift from depolarizing to hyperpolarizing glycine action in rat auditory neurones is due to age-dependent Cl− regulation

    PubMed Central

    Ehrlich, Ingrid; Löhrke, Stefan; Friauf, Eckhard

    1999-01-01

    The inhibitory neurotransmitter glycine can elicit depolarizing responses in immature neurones. We investigated the changes in glycine responses and their ionic mechanism in developing neurones of the rat lateral superior olive (LSO), an auditory brainstem nucleus involved in sound localization. Whole-cell and gramicidin perforated-patch recordings were performed from visually identified LSO neurones in brain slices and glycine was pressure applied for 3–100 ms to the soma. Glycine-evoked currents were reversibly blocked by strychnine. They were mostly monophasic, but biphasic responses occurred in ∼30% of P8-11 neurones in perforated-patch recordings. In whole-cell recordings from P2-11 neurones, the reversal potential of glycine-evoked currents (EGly) was determined by the transmembranous Cl− gradient and corresponded closely to the Nernst potential for Cl−, regardless of age. This indicates that Cl− is the principle ion permeating glycine receptors, but is also consistent with a low relative (10–20%) permeability for HCO3−. The Cl− gradient also determined the polarity and amplitude of glycine-evoked membrane potential changes. Leaving the native intracellular [Cl−] undisturbed with gramicidin perforated-patch recordings, we found a highly significant, age-dependent change of EGly from −46.8 ± 1.8 mV (P1-4, n = 28) to −67.6 ± 3.3 mV (P5-8, n = 10) to −82.2 ± 4.1 mV (P9–11, n = 18). The majority of P1–4 neurones were depolarized by glycine (∼80%) and spikes were evoked in ∼30%. In contrast, P9–11 neurones were hyperpolarized. In perforated-patch recordings, EGly was influenced by the voltage protocol and the glycine application interval; it could be shifted in the positive and negative direction. For a given application interval, these shifts were always larger in P1–4 than in P8–11 neurones, pointing to less effective Cl− regulation mechanisms in younger neurones. Furosemide (frusemide), a blocker of cation

  10. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    SciTech Connect

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2006-03-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  11. Carbonyl traps as potential protective agents against methimazole-induced liver injury.

    PubMed

    Heidari, Reza; Niknahad, Hossein; Jamshidzadeh, Akram; Azarpira, Negar; Bazyari, Mandana; Najibi, Asma

    2015-04-01

    Liver injury is a deleterious adverse effect associated with methimazole administration, and reactive intermediates are suspected to be involved in this complication. Glyoxal is an expected reactive intermediate produced during methimazole metabolism. Current investigation was undertaken to evaluate the role of carnosine, metformin, and N-acetyl cysteine as putative glyoxal (carbonyl) traps, against methimazole-induced hepatotoxicity. Methimazole (100 mg/kg, intraperitoneally) was administered to intact and/or glutathione (GSH)-depleted mice and the role of glyoxal trapping agents was investigated. Methimazole caused liver injury as revealed by an increase in serum alanine aminotransferase and aspartate aminotransferase. Moreover, lipid peroxidation and protein carbonylation occurred significantly in methimazole-treated animals' liver. Hepatic GSH reservoirs were decreased, and inflammatory cells infiltration was observed in liver histopathology. Methimazole-induced hepatotoxicity was severe in GSH-depleted mice and accompanied with interstitial hemorrhage and necrosis of the liver. Glyoxal trapping agents effectively diminished methimazole-induced liver injury both in intact and/or GSH-depleted animals. PMID:25545158

  12. The chemistry of carbonyl compounds in the atmosphere—A review

    NASA Astrophysics Data System (ADS)

    Carlier, P.; Hannachi, H.; Mouvier, G.

    Carbonyl compounds are very important for the trophospheric physico-chemistry because they are the result of the first photo-oxidation stage of almost all organic compounds and they are the essential originators of the free radicals. In the present review we make a synthesis of the studies on the carbonyl compounds chemistry in the trophosphere by successively examining: measurement methods in the trophosphere, sources of primary carbonyl compounds, formation of secondary carbonyl compounds in the atmosphere, reactivity of carbonyl compounds in the atmosphere.

  13. Phenolic carbonyls undergo rapid aqueous photodegradation to form low-volatility, light-absorbing products

    NASA Astrophysics Data System (ADS)

    Smith, Jeremy D.; Kinney, Haley; Anastasio, Cort

    2016-02-01

    We investigated the aqueous photochemistry of six phenolic carbonyls - vanillin, acetovanillone, guaiacyl acetone, syringaldehyde, acetosyringone, and coniferyl aldehyde - that are emitted from wood combustion. The phenolic carbonyls absorb significant amounts of solar radiation and decay rapidly via direct photodegradation, with lifetimes (τ) of 13-140 min under Davis, CA winter solstice sunlight at midday (solar zenith angle = 62°). The one exception is guaiacyl acetone, where the carbonyl group is not directly connected to the aromatic ring: This species absorbs very little sunlight and undergoes direct photodegradation very slowly (τ > 103 min). We also found that the triplet excited states (3C*) of the phenolic carbonyls rapidly oxidize syringol (a methoxyphenol without a carbonyl group), on timescales of 1-5 h for solutions containing 5 μM phenolic carbonyl. The direct photodegradation of the phenolic carbonyls, and the oxidation of syringol by 3C*, both efficiently produce low volatility products, with SOA mass yields ranging from 80 to 140%. Contrary to most aliphatic carbonyls, under typical fog conditions we find that the primary sink for the aromatic phenolic carbonyls is direct photodegradation in the aqueous phase. In areas of significant wood combustion, phenolic carbonyls appear to be small but significant sources of aqueous SOA: over the course of a few hours, nearly all of the phenolic carbonyls will be converted to SOA via direct photodegradation, enhancing the POA mass from wood combustion by approximately 3-5%.

  14. Slow age-dependent decline of doublecortin expression and BrdU labeling in the forebrain from lesser hedgehog tenrecs.

    PubMed

    Alpár, Alán; Künzle, Heinz; Gärtner, Ulrich; Popkova, Yulia; Bauer, Ute; Grosche, Jens; Reichenbach, Andreas; Härtig, Wolfgang

    2010-05-12

    In addition to synaptic remodeling, formation of new neurons is increasingly acknowledged as an important cue for plastic changes in the central nervous system. Whereas all vertebrates retain a moderate neuroproliferative capacity, phylogenetically younger mammals become dramatically impaired in this potential during aging. The present study shows that the lesser hedgehog tenrec, an insectivore with a low encephalization index, preserves its neurogenic potential surprisingly well during aging. This was shown by quantitative analysis of 5-bromo-2'-deoxyuridine (BrdU) immunolabeling in the olfactory bulb, paleo-, archi-, and neocortices from 2- to 7-year-old animals. In addition to these newly born cells, a large number of previously formed immature neurons are present throughout adulthood as shown by doublecortin (DCX) immunostaining in various forebrain regions including archicortex, paleocortex, nucleus accumbens, and amygdala. Several ventricle-associated cells in olfactory bulb and hippocampus were double-labeled by BrdU and DCX immunoreactivity. However, most DCX cells in the paleocortex can be considered as persisting immature neurons that obviously do not enter a differentiation program since double fluorescence labeling does not reveal their co-occurrence with numerous neuronal markers, whereas only a small portion coexpresses the pan-neuronal marker HuC/D. Finally, the present study reveals tenrecs as suitable laboratory animals to study age-dependent brain alterations (e.g., of neurogenesis) or slow degenerative processes, particularly due to the at least doubled longevity of tenrecs in comparison to mice and rats.

  15. Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin.

    PubMed

    Kinn, Patrick M; Holdren, Grant O; Westermeyer, Brittney A; Abuissa, Mousa; Fischer, Carol L; Fairley, Janet A; Brogden, Kim A; Brogden, Nicole K

    2015-06-02

    In the skin, aging is associated with overall epidermal thinning, decreased barrier function, and gradual deterioration of the epidermal immune response. However, the presence and role of cytokines, chemokines, and biologic analytes (CCBAs) in immunosenescence are not known. Here we identified age-related changes in skin properties and CCBAs from stratum corneum of healthy human subjects, providing a means to utilize CCBAs as benchmarks for aging skin health. Transepidermal water loss and a(*) (skin redness) decreased in an age-dependent manner, and were significantly lower (p < 0.05) in Groups 2 (56.6 ± 4.6 years) and 3 (72.9 ± 3.0 years) vs. Group 1 (24.3 ± 2.8 years). In skin wash fluid, 48 CCBAs were detected; seven were significantly lower (p < 0.05) in Groups 2 and 3: EGF, FGF-2, IFNα2, IL-1RA, HSA, keratin-6, and involucrin; cortisol was significantly higher (p < 0.05) in Groups 2 and 3. Our results correspond with the pro-inflammatory shift that occurs with immunosenescence and also provides basis for understanding the inflammatory changes in normal aging skin.

  16. Polyphenols decreased liver NADPH oxidase activity, increased muscle mitochondrial biogenesis and decreased gastrocnemius age-dependent autophagy in aged rats.

    PubMed

    Laurent, Caroline; Chabi, Beatrice; Fouret, Gilles; Py, Guillaume; Sairafi, Badie; Elong, Cecile; Gaillet, Sylvie; Cristol, Jean Paul; Coudray, Charles; Feillet-Coudray, Christine

    2012-09-01

    This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

  17. Age-Dependent Morphologic Alterations in the Outer Retinal and Choroidal Thicknesses Using Swept Source Optical Coherence Tomography

    PubMed Central

    2016-01-01

    Purpose To evaluate the age-dependent morphologic alterations in the outer retina and choroid at the macula using swept-source optical coherence tomography (OCT). Methods Thirty eyes (30 normal subjects; average age, 49 years) were examined; five (age range, third-eighth decades of life) had refractive errors of ±2 diopters or less and no fundus abnormalities. An Early Treatment Diabetic Retinopathy Study (ETDRS) map of the outer retinal and choroidal thickness was constructed using swept-source OCT. The outer retinal and choroidal segmentation lines were drawn automatically, partially manually, within 6 millimeters of the macula. Results The mean outer retinal and choroidal thicknesses in the 6-millimeter-diameter circle were 145±13 and 236±68 microns, respectively. The choroidal thickness and age were negatively (r = -0.66, P<0.01) correlated; the outer retinal thickness and age were not correlated (r = -0.16, P = 0.39). The outer retinal and choroidal thicknesses in the ETDRS map were not correlated (r = -0.13, P = 0.49) within 1 millimeter but correlated (r = 0.32, P<0.01) within 6 millimeters. Conclusions The choroid thins with aging. The outer retina remains stable. Outer retina and choroid are correlated in the entire macula except for the center. ETDRS map can be useful for evaluation of the morphologic relationship between the outer retina and choroid. PMID:27467879

  18. Potato Tuber Blight Resistance Phenotypes Correlate with RB Transgene Transcript Levels in an Age-Dependent Manner.

    PubMed

    Millett, Benjamin P; Gao, Liangliang; Iorizzo, Massimo; Carputo, Domenico; Bradeen, James M

    2015-08-01

    Plants have evolved strategies and mechanisms to detect and respond to pathogen attack. Different organs of the same plant may be subjected to different environments (e.g., aboveground versus belowground) and pathogens with different lifestyles. Accordingly, plants commonly need to tailor defense strategies in an organ-specific manner. Phytophthora infestans, causal agent of potato late blight disease, infects both aboveground foliage and belowground tubers. We examined the efficacy of transgene RB (known for conferring foliar late blight resistance) in defending against tuber late blight disease. Our results indicate that the presence of the transgene has a positive yet only marginally significant effect on tuber disease resistance on average. However, a significant association between transgene transcript levels and tuber resistance was established for specific transformed lines in an age-dependent manner, with higher transcript levels indicating enhanced tuber resistance. Thus, RB has potential to function in both foliage and tuber to impart late blight resistance. Our data suggest that organ-specific resistance might result directly from transcriptional regulation of the resistance gene itself.

  19. Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy.

    PubMed

    McCampbell, Alexander; Truong, David; Broom, Daniel C; Allchorne, Andrew; Gable, Ken; Cutler, Roy G; Mattson, Mark P; Woolf, Clifford J; Frosch, Matthew P; Harmon, Jeffrey M; Dunn, Teresa M; Brown, Robert H

    2005-11-15

    Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. SPTLC1 encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in SPTLC1 cause hereditary sensory and autonomic neuropathy (type I) (HSAN1), an adult onset, autosomal dominant neuropathy. HSAN1 patients have reduced SPT activity. Expression of mutant SPTLC1 in yeast and mammalian cell cultures dominantly inhibits SPT activity. We created transgenic mouse lines that ubiquitously overexpress either wild-type (SPTLC1(WT)) or mutant SPTLC1 (SPTLC1(C133W)). We report here that SPTLC1(C133W) mice develop age-dependent weight loss and mild sensory and motor impairments. Aged SPTLC1(C133W) mice lose large myelinated axons in the ventral root of the spinal cord and demonstrate myelin thinning. There is also a loss of large myelinated axons in the dorsal roots, although the unmyelinated fibers are preserved. In the dorsal root ganglia, IB4 staining is diminished, whereas expression of the injury-induced transcription factor ATF3 is increased. These mice represent a novel mouse model of peripheral neuropathy and confirm the link between mutant SPT and neuronal dysfunction. PMID:16210380

  20. Survival Prediction Score: A Simple but Age-Dependent Method Predicting Prognosis in Patients Undergoing Palliative Radiotherapy

    PubMed Central

    Dalhaug, Astrid; Pawinski, Adam; Haukland, Ellinor

    2014-01-01

    Purpose. Validation of a Canadian three-tiered prognostic model (survival prediction score, SPS) in Norwegian cancer patients referred for palliative radiotherapy (PRT), and evaluation of age-dependent performance of the model. Patients and Methods. We analyzed all 579 PRT courses administered at a dedicated PRT facility between 20.06.07 and 31.12.2009. SPS was assigned as originally described, That is, by taking into consideration three variables: primary cancer type, site of metastases, and performance status. Results. Patients with poor prognosis (non-breast cancer, metastases other than bone, and Karnofsky performance status (KPS) ≤ 60) had median survival of 13 weeks. Those with intermediate prognosis (two of these parameters) survived for a median of 29 weeks, and patients with good prognosis for a median of 114 weeks, P < 0.001. While this model performed well in patients who were 60 years or older, it was less satisfactory in younger patients (no significant difference between the good and intermediate prognosis groups). Conclusion. SPS should mainly be used to predict survival of elderly cancer patients. However, even in this group accuracy is limited because the good prognosis group contained patients with short survival, while the poor prognosis group contained long-term survivors. Thus, improved models should be developed. PMID:25006508

  1. Age-dependent occurrence of an ascending axon on the omega neuron of the cricket, Teleogryllus oceanicus.

    PubMed

    Atkins, G; Pollack, G S

    1986-01-22

    The omega neurons (ON1s) are a mirror-symmetrical pair of identified prothoracic auditory interneurons of crickets which have been previously described as intraganglionic. Using intracellular techniques we stained ON1s of female Teleogryllus oceanicus and found that many ON1s have axons which project anteriorly out of the prothoracic ganglion. The ascending axon arises contralateral to the soma at the most anteriolateral bend of the bow-shaped process of an otherwise "archetypical" ON1 and travels up the neck connective in a ventral position just inside the connective tissue sheath. The occurrence of the ascending axon is age-dependent. Seventy-five percent of ON1s stained in late nymphal stages and in young adults had an ascending axon while only 30% of ON1s in older adults had an ascending axon. Evidence is presented to show that ON1s having ascending axons are developmental variants of the "archetypical" ON1 and do not represent a separate neuron type. The two morphological types of ON1s are not distinguishable on the basis of their responses to sound stimuli having carrier frequencies of 3.5-60 kHz. Although we know that the ascending axon conducts action potentials, its target and terminal morphology are not yet known.

  2. FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.

    PubMed

    Lublin, Alex; Isoda, Fumiko; Patel, Harshil; Yen, Kelvin; Nguyen, Linda; Hajje, Daher; Schwartz, Marc; Mobbs, Charles

    2011-01-01

    Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.

  3. Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples.

    PubMed

    Gillespie, Anna K; Jones, Emily A; Lin, Yuan-Hung; Karlsson, Mattias P; Kay, Kenneth; Yoon, Seo Yeon; Tong, Leslie M; Nova, Philip; Carr, Jessie S; Frank, Loren M; Huang, Yadong

    2016-05-18

    Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), but the mechanism by which it causes cognitive decline is unclear. In knockin (KI) mice, human apoE4 causes age-dependent learning and memory impairments and degeneration of GABAergic interneurons in the hippocampal dentate gyrus. Here we report two functional apoE4-KI phenotypes involving sharp-wave ripples (SWRs), hippocampal network events critical for memory processes. Aged apoE4-KI mice had fewer SWRs than apoE3-KI mice and significantly reduced slow gamma activity during SWRs. Elimination of apoE4 in GABAergic interneurons, which prevents learning and memory impairments, rescued SWR-associated slow gamma activity but not SWR abundance in aged mice. SWR abundance was reduced similarly in young and aged apoE4-KI mice; however, the full SWR-associated slow gamma deficit emerged only in aged apoE4-KI mice. These results suggest that progressive decline of interneuron-enabled slow gamma activity during SWRs critically contributes to apoE4-mediated learning and memory impairments. VIDEO ABSTRACT.

  4. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

    PubMed

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-07-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  5. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    PubMed Central

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

  6. Nuclear chemistry. Synthesis and detection of a seaborgium carbonyl complex.

    PubMed

    Even, J; Yakushev, A; Düllmann, Ch E; Haba, H; Asai, M; Sato, T K; Brand, H; Di Nitto, A; Eichler, R; Fan, F L; Hartmann, W; Huang, M; Jäger, E; Kaji, D; Kanaya, J; Kaneya, Y; Khuyagbaatar, J; Kindler, B; Kratz, J V; Krier, J; Kudou, Y; Kurz, N; Lommel, B; Miyashita, S; Morimoto, K; Morita, K; Murakami, M; Nagame, Y; Nitsche, H; Ooe, K; Qin, Z; Schädel, M; Steiner, J; Sumita, T; Takeyama, M; Tanaka, K; Toyoshima, A; Tsukada, K; Türler, A; Usoltsev, I; Wakabayashi, Y; Wang, Y; Wiehl, N; Yamaki, S

    2014-09-19

    Experimental investigations of transactinoide elements provide benchmark results for chemical theory and probe the predictive power of trends in the periodic table. So far, in gas-phase chemical reactions, simple inorganic compounds with the transactinoide in its highest oxidation state have been synthesized. Single-atom production rates, short half-lives, and harsh experimental conditions limited the number of experimentally accessible compounds. We applied a gas-phase carbonylation technique previously tested on short-lived molybdenum (Mo) and tungsten (W) isotopes to the preparation of a carbonyl complex of seaborgium, the 106th element. The volatile seaborgium complex showed the same volatility and reactivity with a silicon dioxide surface as those of the hexacarbonyl complexes of the lighter homologs Mo and W. Comparison of the product's adsorption enthalpy with theoretical predictions and data for the lighter congeners supported a Sg(CO)6 formulation.

  7. Nuclear chemistry. Synthesis and detection of a seaborgium carbonyl complex.

    PubMed

    Even, J; Yakushev, A; Düllmann, Ch E; Haba, H; Asai, M; Sato, T K; Brand, H; Di Nitto, A; Eichler, R; Fan, F L; Hartmann, W; Huang, M; Jäger, E; Kaji, D; Kanaya, J; Kaneya, Y; Khuyagbaatar, J; Kindler, B; Kratz, J V; Krier, J; Kudou, Y; Kurz, N; Lommel, B; Miyashita, S; Morimoto, K; Morita, K; Murakami, M; Nagame, Y; Nitsche, H; Ooe, K; Qin, Z; Schädel, M; Steiner, J; Sumita, T; Takeyama, M; Tanaka, K; Toyoshima, A; Tsukada, K; Türler, A; Usoltsev, I; Wakabayashi, Y; Wang, Y; Wiehl, N; Yamaki, S

    2014-09-19

    Experimental investigations of transactinoide elements provide benchmark results for chemical theory and probe the predictive power of trends in the periodic table. So far, in gas-phase chemical reactions, simple inorganic compounds with the transactinoide in its highest oxidation state have been synthesized. Single-atom production rates, short half-lives, and harsh experimental conditions limited the number of experimentally accessible compounds. We applied a gas-phase carbonylation technique previously tested on short-lived molybdenum (Mo) and tungsten (W) isotopes to the preparation of a carbonyl complex of seaborgium, the 106th element. The volatile seaborgium complex showed the same volatility and reactivity with a silicon dioxide surface as those of the hexacarbonyl complexes of the lighter homologs Mo and W. Comparison of the product's adsorption enthalpy with theoretical predictions and data for the lighter congeners supported a Sg(CO)6 formulation. PMID:25237098

  8. Metal Carbonyl-Hydrosilane Reactions and Hydrosilation Catalysis

    SciTech Connect

    Cutler, A. R.

    2001-04-14

    Manganese carbonyl complexes serve as hydrosilation precatalysts for selectively transforming a carbonyl group into a siloxy methylene or a fully reduced methylene group. Substrates of interest include (1) aldehydes, ketones, carboxylic acids, silyl esters, and esters, and (2) their organometallic acyl counterparts. Three relevant catalytic reactions are shown. Two types of manganese precatalysts have been reported: (a) alkyl and acyl complexes (L)(C0){sub 4}MnR [L = CO, PPh{sub 3}; R = COCH{sub 3}, COPh, CH{sub 3}] and (b) halides (CO){sub 5}MnX and [(CO){sub 4}MnX]{sub 2} (X = Br, I). The former promote hydrosilation and deoxygenation catalysis; the latter promote dehydrogenative silation of alcohols and carboxylic acids as well as hydrosilation and deoxygenation of some metallocarboxylic acid derivatives. In every case studied, these Mn precatalysts are far more reactive or selective than traditional Rh(I) precatalysts.

  9. Round Robin analysis of alcolol and carbonyl synthetic exhaust samples

    SciTech Connect

    Clark, W.L.; Biller, W.F.; Tejada, S.B.; Siegl, W.O.; Jensen, T.E.

    1994-07-25

    Recent changes in regulatory practices have brought about a need for speciated analysis of the volatile organic components of vehicle exhaust. The purpose of the study was to allow interested laboratories to participate in a Round Robin so that each could assess their speciation methodologies. 'Synthetic exhaust' samples were prepared of mixed DN-carbonyl standards deposited on DNPH-coated cartridges, and solutions of alcohol in water. The fifteen participating laboratories included automotive, contract, petroleum, and regulatory organizations. The results described in this paper consider only variability asociated with the analytical measurement of the samples that have already been collected in impingers or on cartridges. In general, alochols (methanol and ethanol) were quantified without difficulty. With the exception of acrolein and crotonaldehyde, the quantitation of the carbonyl samples was fairly good considering the variety of analytical methods that were employed.

  10. Round robin analysis of alcohol and carbonyl synthetic exhaust samples

    SciTech Connect

    Clark, W.L.; Biller, W.F.; Tejada, S.B.; Siegl, W.O.; Rosenhamer, D.; Newkirk, M.S.; Crowley, R.J.

    1994-10-01

    Recent changes in regulatory practices have brought about a need for speciated analysis of the volatile organic components of vehicle exhaust. The purpose of this study was to allow interested laboratories to participate in a Round Robin so that each could assess their speciation methodologies. `Synthetic exhaust` samples were prepared of mixed DNPH-carbonyl standards deposited on DNPH cartridges, and solutions of alcohol in water. The fifteen participating laboratories included automotive, contract, petroleum and regulatory organizations. The results described in this paper consider only variability associated with the analyltical measurement of samples that have already been collected in impingers or on cartridges. In general, alcohols (methanol and ethanol) were quantified without difficulty. With the exception of acrolein and crotonaldehyde, the quantitation of the carbonyl samples was very good considering the variety of analytical methods that were used. 9 refs., 4 figs., 12 tabs.

  11. Hydrogenation of coal liquid utilizing a metal carbonyl catalyst

    DOEpatents

    Feder, Harold M.; Rathke, Jerome W.

    1979-01-01

    Coal liquid having a dissolved transition metal, catalyst as a carbonyl complex such as Co.sub.2 (CO.sub.8) is hydrogenated with hydrogen gas or a hydrogen donor. A dissociating solvent contacts the coal liquid during hydrogenation to form an immiscible liquid mixture at a high carbon monoxide pressure. The dissociating solvent, e.g. ethylene glycol, is of moderate coordinating ability, while sufficiently polar to solvate the transition metal as a complex cation along with a transition metal, carbonyl anion in solution at a decreased carbon monoxide pressure. The carbon monoxide pressure is reduced and the liquids are separated to recover the hydrogenated coal liquid as product. The dissociating solvent with the catalyst in ionized form is recycled to the hydrogenation step at the elevated carbon monoxide pressure for reforming the catalyst complex within fresh coal liquid.

  12. Synthetic and mechanistic aspects of titanium-mediated carbonyl olefinations

    SciTech Connect

    Petasis, N.A.; Staszewski, J.P.; Hu, Yong-Han; Lu, Shao-Po

    1995-12-31

    A new method for the olefination of carbonyl compounds with dimethyl titanocene, and other related bishydrocarbyl titanocene derivatives has been recently developed in the author`s laboratories. This process is experimentally convenient and works with various types of carbonyl compounds, including aldehydes, ketones, esters, lactones, carbonates, anhydrides, amides, imides, lactams, thioesters, selenoesters, and acylsilanes. More recent studies have focused on the scope and utility of this reaction, including mechanistic studies and synthetic applications. In addition to varying the reaction conditions, the authors have examined several mixed titanocene derivatives and have found ways for carrying out this type of olefination at room temperature, such as the use of tris(trimethylsilyl) titanacyclobutene. The authors have also employed this reaction in the modification of carbohydrates and cyclobutenediones. This olefination was also followed-up with subsequent transformations to produce carbocycles and heterocycles, including tetrahydrofurans and tetrahydropyrans.

  13. The modulation of carbonyl reductase 1 by polyphenols.

    PubMed

    Boušová, Iva; Skálová, Lenka; Souček, Pavel; Matoušková, Petra

    2015-01-01

    Carbonyl reductase 1 (CBR1), an enzyme belonging to the short-chain dehydrogenases/reductases family, has been detected in all human tissues. CBR1 catalyzes the reduction of many xenobiotics, including important drugs (e.g. anthracyclines, nabumetone, bupropion, dolasetron) and harmful carbonyls and quinones. Moreover, it participates in the metabolism of a number of endogenous compounds and it may play a role in certain pathologies. Plant polyphenols are not only present in many human food sources, but are also a component of many popular dietary supplements and herbal medicines. Many studies reviewed herein have demonstrated the potency of certain flavonoids, stilbenes and curcuminoids in the inhibition of the activity of CBR1. Interactions of these polyphenols with transcriptional factors, which regulate CBR1 expression, have also been reported in several studies. As CBR1 plays an important role in drug metabolism as well as in the protection of the organism against potentially harmful carbonyls, the modulation of its expression/activity may have significant pharmacological and/or toxicological consequences. Some polyphenols (e.g. luteolin, apigenin and curcumin) have been shown to be very potent CBR1 inhibitors. The inhibition of CBR1 seems useful regarding the increased efficacy of anthracycline therapy, but it may cause the worse detoxification of reactive carbonyls. Nevertheless, all known information about the interactions of polyphenols with CBR1 have only been based on the results of in vitro studies. With respect to the high importance of CBR1 and the frequent consumption of polyphenols, in vivo studies would be very helpful for the evaluation of risks/benefits of polyphenol interactions with CBR1.

  14. Strongly driven quantum pendulum of the carbonyl sulfide molecule

    NASA Astrophysics Data System (ADS)

    Trippel, Sebastian; Mullins, Terry; Müller, Nele L. M.; Kienitz, Jens S.; Omiste, Juan J.; Stapelfeldt, Henrik; González-Férez, Rosario; Küpper, Jochen

    2014-05-01

    We demonstrate and analyze a strongly driven quantum pendulum in the angular motion of state-selected and laser-aligned carbonyl sulfide molecules. Raman couplings during the rising edge of a 50-ps laser pulse create a wave packet of pendular states, which propagates in the confining potential formed by the polarizability interaction between the molecule and the laser field. This wave-packet dynamics manifests itself as pronounced oscillations in the degree of alignment with a laser-intensity-dependent period.

  15. Iron(III)-catalysed carbonyl-olefin metathesis.

    PubMed

    Ludwig, Jacob R; Zimmerman, Paul M; Gianino, Joseph B; Schindler, Corinna S

    2016-04-27

    The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.

  16. Iron(III)-catalysed carbonyl-olefin metathesis

    NASA Astrophysics Data System (ADS)

    Ludwig, Jacob R.; Zimmerman, Paul M.; Gianino, Joseph B.; Schindler, Corinna S.

    2016-05-01

    The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.

  17. Method for determination of some soluble atmospheric carbonyl compounds

    SciTech Connect

    Lee, Y.N.; Zhou, X. )

    1993-04-01

    A technique was developed for the measurement of soluble atmospheric carbonyl compounds, which uses a pyrex coil gas-liquid scrubber sampler in conjunction with a high-performance liquid chromatograph equipped with a UV-visible detector for separation and identification following derivatization with 2,4-dinitrophenylhydrazine. Carbonyls exhibiting a Henry's law solubility similar to or greater than that of formaldehyde (FA) can be determined by this method; these include FA, glycolaldehyde (GA), glyoxal (GL), and methylglyoxal (MG). Based on liquid standards and field-developed chromatographic characteristics, the limits of detection are about 0.005 ppb (in the gas phase) for MG, about 0.01 ppb for GL, and about 0.02 ppb for FA and GA. Because of the short air-liquid contact time in the coil sampler (smaller than 10 s), interferences from aqueous-phase reactions of ozone are insignificant. Also, at the low pH of the scrubbing solution, interference resulting from reactions of carbonyls with S(IV) is unimportant. 43 refs., 7 figs., 3 tabs.

  18. Iron(III)-catalysed carbonyl-olefin metathesis.

    PubMed

    Ludwig, Jacob R; Zimmerman, Paul M; Gianino, Joseph B; Schindler, Corinna S

    2016-05-19

    The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis. PMID:27120158

  19. 40 CFR 721.10409 - Poly(oxyalkylenediyl), .alpha.-[[[methyl-3-[[[(polyfluoroalkyl)oxy]carbonyl] amino]phenyl]amino...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Poly(oxyalkylenediyl), .alpha...(oxyalkylenediyl), .alpha.- carbonyl] amino]phenyl]amino]carbonyl]- .omega.-methoxy-(generic). (a) Chemical... as poly(oxyalkylenediyl), .alpha.- carbonyl]amino]phenyl]amino] carbonyl]-.omega.-methoxy- (PMN...

  20. 40 CFR 721.10409 - Poly(oxyalkylenediyl), .alpha.-[[[methyl-3-[[[(polyfluoroalkyl) oxy]carbonyl]amino]phenyl]amino...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Poly(oxyalkylenediyl), .alpha...(oxyalkylenediyl), .alpha.- carbonyl]amino]phenyl]amino] carbonyl]-.omega.-methoxy- (generic). (a) Chemical... as poly(oxyalkylenediyl), .alpha.- carbonyl]amino]phenyl]amino] carbonyl]-.omega.-methoxy- (PMN...

  1. Unilateral whisker clipping exacerbates ethanol-induced social and somatosensory behavioral deficits in a sex- and age-dependent manner.

    PubMed

    Wellmann, Kristen A; Mooney, Sandra M

    2015-09-01

    Prenatal exposure to ethanol results in sensory deficits and altered social interactions in animal and clinical populations. Sensory stimuli serve as important cues and shape sensory development; developmental exposure to ethanol or sensory impoverishment can impair somatosensory development, but their combined effects on behavioral outcomes are unknown. We hypothesized 1) that chronic prenatal ethanol exposure would disrupt social interaction and somatosensory performance during adolescence, 2) that a mild sensory impoverishment (neonatal unilateral whisker clipping; WC) would have a mildly impairing to sub-threshold effect on these behavioral outcomes, and 3) that the effect of ethanol would be exacerbated by WC. Long-Evans dams were fed a liquid diet containing ethanol or pair-fed with a non-ethanol diet on gestational days (G) 6-G21. Chow-fed control animals were also included. One male and female pup per litter underwent WC on postnatal day (P)1, P3, and P5. Controls were unclipped. Offspring underwent social interaction on P28 or P42, and gap-crossing (GC) on P31 or P42. Ethanol-exposed pups played less and crossed shorter gaps than control pups regardless of age or sex. WC further exacerbated ethanol-induced play fighting and GC deficits in all males but only in 28-day-old females. WC alone reduced sniffing in all males and in younger females. Thus, prenatal ethanol exposure induced deficits in social interaction and somatosensory performance during adolescence. Sensory impoverishment exacerbates ethanol's effect in 28-day-old male and female animals and in 42-day-old males, suggesting sex- and age-dependent changes in outcomes in ethanol-exposed offspring.

  2. Age-dependent survival of island vs. mainland populations of two avian scavengers: delving into migration costs.

    PubMed

    Sanz-Aguilar, Ana; De Pablo, Félix; Donázar, José Antonio

    2015-10-01

    Large terrestrial long-lived birds (including raptors) are typically sedentary on islands, even when they are migratory on the mainland. Density-dependent variation in the age at first breeding has been described as responsible for the long-term persistence of long-lived bird populations on islands. However, sedentary island populations may also benefit from higher survival rates derived from the absence of migration costs, especially for young individuals. Thus, sedentary island populations can mimic a natural experiment to study migration costs. We estimated the age-dependent survival of two sedentary raptors on the island of Menorca (Egyptian vultures Neophron percnopterus and red kites Milvus milvus) and compared these estimates with those reported for other migratory and sedentary populations. In Menorca, Egyptian vultures, but not red kites, showed low levels of human-related mortality resulting in extremely high survival probabilities, probably due to different diet choices and behavioral patterns. Juvenile Egyptian vultures and red kites in the studied population had lower survival probabilities than adults. This difference, however, was smaller than those reported for mainland migrant populations, which showed a lower juvenile survival rate. In fact, between-population comparisons suggested that survival of the young in migrant populations may be triggered by mortality factors in wintering areas. In contrast, adult survival may respond to mortality factors in breeding areas. Our results suggest that raptor species that become sedentary on islands may benefit from higher pre-breeder survival prospects in comparison with their mainland migrant counterparts. This fact, in combination with an earlier age at first reproduction, may facilitate their persistence. PMID:26013875

  3. Age-dependent survival of island vs. mainland populations of two avian scavengers: delving into migration costs.

    PubMed

    Sanz-Aguilar, Ana; De Pablo, Félix; Donázar, José Antonio

    2015-10-01

    Large terrestrial long-lived birds (including raptors) are typically sedentary on islands, even when they are migratory on the mainland. Density-dependent variation in the age at first breeding has been described as responsible for the long-term persistence of long-lived bird populations on islands. However, sedentary island populations may also benefit from higher survival rates derived from the absence of migration costs, especially for young individuals. Thus, sedentary island populations can mimic a natural experiment to study migration costs. We estimated the age-dependent survival of two sedentary raptors on the island of Menorca (Egyptian vultures Neophron percnopterus and red kites Milvus milvus) and compared these estimates with those reported for other migratory and sedentary populations. In Menorca, Egyptian vultures, but not red kites, showed low levels of human-related mortality resulting in extremely high survival probabilities, probably due to different diet choices and behavioral patterns. Juvenile Egyptian vultures and red kites in the studied population had lower survival probabilities than adults. This difference, however, was smaller than those reported for mainland migrant populations, which showed a lower juvenile survival rate. In fact, between-population comparisons suggested that survival of the young in migrant populations may be triggered by mortality factors in wintering areas. In contrast, adult survival may respond to mortality factors in breeding areas. Our results suggest that raptor species that become sedentary on islands may benefit from higher pre-breeder survival prospects in comparison with their mainland migrant counterparts. This fact, in combination with an earlier age at first reproduction, may facilitate their persistence.

  4. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  5. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  6. Persistent changes of corticostriatal plasticity in dt(sz) mutant hamsters after age-dependent remission of dystonia.

    PubMed

    Avchalumov, Y; Volkmann, C E; Rückborn, K; Hamann, M; Kirschstein, T; Richter, A; Köhling, R

    2013-10-10

    Abnormal plasticity in the cortico-basal ganglia-thalamocortical loop has been suggested to represent a key factor in the pathophysiology of dystonia. In a model of primary paroxysmal dystonia, the dt(sz) mutant hamster, previous experiments have shown a strongly increased long-term potentiation (LTP) in comparison to non-dystonic control hamsters. These basal changes, i.e. in the absence of dystonia, were found in young animals at an age of 5 weeks, when the age-dependent dystonia in dt(sz) mutant reaches highest severity. In the present study we examined in corticostriatal slices (1) whether the increases in synaptic plasticity can be modulated by stressful stimuli which induce dystonic episodes in young mutant hamsters, and (2) whether increases of LTP persist after spontaneous remission of dystonia in animals older than 10 weeks. The present data show that in slices of young mutant hamsters the extent of LTP was not influenced by the presence of dystonia: In comparison to age-matched control hamsters, LTP was increased in mutant hamsters independent of preceding stressful stimulation. After remission of dystonia, i.e., in older dt(sz) mutant hamsters >10 weeks, only LTP could be elicited, while in preparations from age-matched control hamsters, either LTP or long-term depression developed, depending on previous behavioral challenge. We conclude that in mature brain, corticostriatal connections have the potential for changes in metaplasticity, while in dt(sz) mutant hamsters this metaplasticity is persistently infringed even though stress-inducible dystonic symptoms are lost.

  7. Age Dependency of GLI Reference Values Compared with Paediatric Lung Function Data in Two German Studies (GINIplus and LUNOKID)

    PubMed Central

    Hüls, Anke; Krämer, Ursula; Gappa, Monika; Müller-Brandes, Christine; Schikowski, Tamara; von Berg, Andrea; Hoffmann, Barbara; Schuster, Antje; Wisbauer, Matthias; Flexeder, Claudia; Heinrich, Joachim; Schulz, Holger; Berdel, Dietrich

    2016-01-01

    A hallmark of the newly published GLI (Global Lungs Initiative) spirometric reference values is their "all-age" (3-95yr) predictive power, accomplished by incorporating non-linear age dependencies into modelling parameters. This modelling strategy is especially promising for the age range of puberty; however, the performance of GLI-values for adolescents is currently unknown. We calculated GLI-based z-scores for children/adolescents without apparent respiratory diseases from two different German studies, LUNOKID (N = 1943, 4–19 years) and GINIplus (N = 1042, 15 years) and determined the goodness of fit for specific age groups. We defined fit sufficient if the absolute mean of z-scores was <0.5. For children (<10yr) the mean GLI-based z-scores for FEV1 and FVC reached a good fit with mean z-scores for FEV1 between -0.11 and 0.01 and mean z-scores for FVC between 0.01 and 0.16, but larger deviations were observed in adolescents, especially boys (mean z-score -0.58 for FEV1 and -0.57 for FVC in GINIplus). The fit for FEV1/FVC was sufficient. GLI reference values provided reasonable estimates for the individuals enrolled in our studies, which span the age range of lung growth and development. However, we found that GLI-predictions overestimated lung volumes, especially those for German adolescent boys, which may, left unrecognised, lead to erroneous diagnosis of lung disease. Caution should be taken when applying these reference values to epidemiologic studies. PMID:27438002

  8. Glucolipotoxicity age-dependently impairs beta cell function in rats despite a marked increase in beta cell mass

    PubMed Central

    Fontés, G.; Zarrouki, B.; Hagman, D. K.; Latour, M. G.; Semache, M.; Roskens, V.; Moore, P. C.; Prentki, M.; Rhodes, C. J.; Jetton, T. L.

    2010-01-01

    Aims/hypothesis Prolonged exposure of pancreatic beta cells to excessive levels of glucose and fatty acids, referred to as glucolipotoxicity, is postulated to contribute to impaired glucose homeostasis in patients with type 2 diabetes. However, the relative contribution of defective beta cell function vs diminished beta cell mass under glucolipotoxic conditions in vivo remains a subject of debate. We therefore sought to determine whether glucolipotoxicity in rats is due to impaired beta cell function and/or reduced beta cell mass, and whether older animals are more susceptible to glucolipotoxic condition. Methods Wistar rats (2 and 6 months old) received a 72 h infusion of glucose + intravenous fat emulsion or saline control. In vivo insulin secretion and sensitivity were assessed by hyperglycaemic clamps. Ex vivo insulin secretion, insulin biosynthesis and gene expression were measured in isolated islets. Beta cell mass and proliferation were examined by immunohistochemistry. Results A 72 h infusion of glucose + intravenous fat emulsion in 2-month-old Wistar rats did not affect insulin sensitivity, insulin secretion or beta cell mass. In 6-month-old rats by contrast it led to insulin resistance and reduced insulin secretion in vivo, despite an increase in beta cell mass and proliferation. This was associated with: (1) diminished glucose-stimulated second-phase insulin secretion and proinsulin biosynthesis; (2) lower insulin content; and (3) reduced expression of beta cell genes in isolated islets. Conclusions/interpretation In this in vivo model, glucolipotoxicity is characterised by an age-dependent impairment of glucose-regulated beta cell function despite a marked increase in beta cell mass. PMID:20628728

  9. Age-Dependent Biochemical Dysfunction in Skeletal Muscle of Triple-Transgenic Mouse Model of Alzheimer`s Disease

    PubMed Central

    Monteiro-Cardoso, Vera F.; Castro, Marisa; Oliveira, M.M.; Moreira, Paula I.; Peixoto, Francisco; A.Videira, Romeu

    2015-01-01

    The emergence of Alzheimer`s disease as a systemic pathology shifted the research paradigm toward a better understanding of the molecular basis of the disease considering the pathophysiological changes in both brain and peripheral tissues. In the present study, we evaluated the impact of disease progression on physiological relevant features of skeletal muscle obtained from 3, 6 and 12 month-old 3xTg-AD mice, a model of Alzheimer`s disease, and respective agematched nonTg mice. Our results showed that skeletal muscle functionality is already affected in 3-month-old 3xTg-AD mice as evidenced by deficient acetylcholinesterase and catalase activities as well as by alterations in fatty acid composition of mitochondrial membranes. Additionally, an age-dependent accumulation of amyloid-β1-40 peptide occurred in skeletal muscle of 3xTg-AD mice, an effect that preceded bioenergetics mitochondrial dysfunction, which was only detected at 12 months of age, characterized by decreased respiratory control ratio and ADP/O index and by an impairment of complex I activity. HPLC-MS/MS analyses revealed significant changes in phospholipid composition of skeletal muscle tissues from 3xTg-AD mice with 12 months of age when compared with age-matched nonTg mice. Increased levels of lyso-phosphatidylcholine associated with a decrease of phosphatidylcholine molecular species containing arachidonic acid were detected in 3xTg-AD mice, indicating an enhancement of phospholipase A2 activity and skeletal muscle inflammation. Additionally, a decrease of phosphatidylethanolamine plasmalogens content and an increase in phosphatidylinositol levels was observed in 3xTg-AD mice when compared with age-matched nonTg mice. Altogether, these observations suggest that the skeletal muscle of 3xTg-AD mice are more prone to oxidative and inflammatory events. PMID:25654504

  10. BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication.

    PubMed

    Schmidt, T; Adam, C; Hirsch, H H; Janssen, M W W; Wolf, M; Dirks, J; Kardas, P; Ahlenstiel-Grunow, T; Pape, L; Rohrer, T; Fliser, D; Sester, M; Sester, U

    2014-06-01

    BK polyomavirus (BKPyV) infection is widespread and typically asymptomatic during childhood, but may cause nephropathy in kidney transplant recipients. However, there is only limited knowledge on BKPyV-specific immunity in children and adults, and its role in BKPyV-replication and disease posttransplant. We therefore characterized BKPyV-specific immunity from 122 immunocompetent individuals (1-84 years), 38 adult kidney recipients with (n = 14) and without BKPyV-associated complications (n = 24), and 25 hemodialysis (HD) patients. Blood samples were stimulated with overlapping peptides of BKPyV large-T antigen and VP1 followed by flow-cytometric analysis of activated CD4 T cells expressing interferon-γ, IL-2 and tumor necrosis factor-α. Antibody-levels were determined using enzyme-linked immunosorbent assay. Both BKPyV-IgG levels and BKPyV-specific CD4 T cell frequencies were age-dependent (p = 0.0059) with maximum levels between 20 and 30 years (0.042%, interquartile range 0.05%). Transplant recipients showed a significantly higher BKPyV-specific T cell prevalence (57.9%) compared to age-matched controls (21.7%) or HD patients (28%, p = 0.017). Clinically relevant BKPyV-replication was associated with elevated frequencies of BKPyV-specific T cells (p = 0.0002), but decreased percentage of cells expressing multiple cytokines (p = 0.009). In conclusion, BKPyV-specific cellular immunity reflects phases of active BKPyV-replication either after primary infection in childhood or during reactivation after transplantation. Combined analysis of BKPyV-specific T cell functionality and viral loads may improve individual risk assessment.

  11. Highly carbonylated cellulose nanofibrous membranes utilizing maleic anhydride grafting for efficient lysozyme adsorption.

    PubMed

    Ma, Juncheng; Wang, Xueqin; Fu, Qiuxia; Si, Yang; Yu, Jianyong; Ding, Bin

    2015-07-22

    Construction of adsorptive materials for simple, efficient, and high-throughput adsorption of proteins is critical to meet the great demands of highly purified proteins in biotechnological and biopharmaceutical industry; however, it has proven extremely challenging. Here, we report a cost-effective strategy to create carbonyl groups surface-functionalized nanofibrous membranes under mild conditions for positively charged protein adsorption. Our approach allows maleic anhydride to in situ graft on cellulose nanofibrous membranes (CMA) to construct adsorptive membranes with large surface area and tortuous porous structure. Thereby, the resultant CMA membranes exhibited high adsorption capacity of 160 mg g(-1), fast equilibrium within 12 h, and good reversibility to lysozyme. Moreover, the dynamic adsorption was performed under low pressure-drops (750 Pa), with a relatively high saturation adsorption amount of 118 mg g(-1), which matched well with the requirements for proteins purification. Considering the excellent adsorption performance of the as-prepared adsorptive membranes, this simple and intriguing approach may pave a way for the design and development of robust and cost-effective adsorption membranes to meet the great demands for fast and efficient adsorption of positively charged proteins.

  12. Ambient levels of carbonyl compounds and their sources in Guangzhou, China

    NASA Astrophysics Data System (ADS)

    Feng, Yanli; Wen, Sheng; Chen, Yingjun; Wang, Xinming; Lü, Huixiong; Bi, Xinhui; Sheng, Guoying; Fu, Jiamo

    Ambient levels of carbonyl compounds and their possible sources, vehicular exhaust and cooking exhaust, were studied at seven places in Guangzhou, including five districts (a residential area, an industrial area, a botanical garden, a downtown area and a semi-rural area), a bus station and a restaurant during the period of June-September 2003. Nineteen carbonyl compounds were identified in the ambient air, of which acetone was the most abundant carbonyl, followed by formaldehyde and acetaldehyde. Only little changes were found in carbonyl concentration levels in the five different districts because of their dispersion and mixture in the atmosphere in summer. The lower correlations between the carbonyls' concentrations might result from the mixture of carbonyls derived from different sources, including strong photochemical reactions at noon in summer. Formaldehyde and acetaldehyde were the main carbonyls in bus station, while straight-chain carbonyls were comparatively abundant in cooking exhaust. Besides vehicular exhaust, cooking might be another major source of carbonyl compounds in Guangzhou City, especially for high molecular weight carbonyls.

  13. [Chemical Characteristics and Sources of Atmospheric Carbonyls During the 2014 Beijing APEC].

    PubMed

    He, Xiao-lang; Tan, Ji-hua; Guo, Song-jun; Ma, Yong-liang; He, Ke-bin

    2016-03-15

    Pollution characteristic and variation trend of atmospheric carbonyls were investigated in November during the 2014 Beijing APEC. Formaldehyde, acetaldehyde and acetone were the dominant carbonyls, accounting for 82.66% of total carbonyls, and especially, formaldehyde accounted for 40.12% of total carbonyls. Atmospheric concentrations of total carbonyls decreased by around 64.10% after the clean air policy was carried out during the Beijing APEC, and the variation trend of carbonyls showed a similar pattern to those of other pollutants like PM₂.₅ during the APEC. Strong correlations (R² of 0.67-0.98) were observed among formaldehyde, acetaldehyde, acetone and total carbonyls during and after the APEC, indicating that they had similar sources; however, poor correlations (R² of -0.11-0.42 and 0.16-0.94, respectively) were observed before the APEC, implying different emission sources for ambient carbonyls. The calculated ratios of C1/C2, C2/C3 and OC/EC indicated that both vehicles and coal emissions were responsible for atmospheric carbonyls before the APEC, and emissions from coal burning were the major contributor to atmospheric carbonyls during and after the APEC, especially after the APEC. PMID:27337869

  14. On-road measurement of carbonyls in California light-duty vehicle emissions.

    PubMed

    Kean, A J; Grosjean, E; Grosjean, D; Harley, R A

    2001-11-01

    Emissions of carbonyls by motor vehicles are of concern because these species can be hazardous to human health and highly reactive in the atmosphere. The objective of this research was to measure carbonyl emission factors for California light-duty motor vehicles. Measurements were made at the entrance and exit of a San Francisco Bay area highway tunnel, in the center bore where heavy-duty trucks are not allowed. During summer 1999, approximately 100 carbonyls were identified, including saturated aliphatic aldehydes and ketones, unsaturated aliphatic carbonyls, aliphatic dicarbonyls, and aromatic carbonyls. Concentrations were measured for 32 carbonyls and were combined with NMOC, CO, and CO2 concentrations to calculate by carbon balance emission factors per unit of fuel burned. The measured carbonyl mass emitted from light-duty vehicles was 68 +/- 4 mg L(-1). Formaldehyde accounted for 45% of the measured mass emissions, acetaldehyde 12%, tolualdehydes 10%, benzaldehyde 7.2%, and acetone 5.9%. The ozone forming potential of the carbonyl emissions was dominated by formaldehyde (70%) and acetaldehyde (14%). Between 1994 and 1999, emission factors measured at the same tunnel for formaldehyde, acetaldehyde, and benzaldehyde decreased by 45-70%. Carbonyls constituted 3.9% of total NMOC mass emissions and 5.2% of NMOC reactivity. A comparison of carbonyl emissions with gasoline composition supports previous findings that aromatic aldehyde emissions are related to aromatics in gasoline. Carbonyl concentrations in liquid gasoline were also measured. Acetone and MEK were the most abundant carbonyls in unburned gasoline; eight other carbonyls were detected and quantified.

  15. Carbonyl Stress in Aging Process: Role of Vitamins and Phytochemicals as Redox Regulators

    PubMed Central

    Ergin, Volkan; Hariry, Reza Ebrahimi; Karasu, Çimen

    2013-01-01

    There is a growing scientific agreement that the cellular redox regulators such as antioxidants, particularly the natural polyphenolic forms, may help lower the incidence of some pathologies, including metabolic diseases like diabetes and diabesity, cardiovascular and neurodegenerative abnormalities, and certain cancers or even have anti-aging properties. The recent researches indicate that the degree of metabolic modulation and adaptation response of cells to reductants as well as oxidants establish their survival and homeostasis, which is linked with very critical balance in imbalances in cellular redox capacity and signaling, and that might be an answer the questions why some antioxidants or phytochemicals potentially could do more harm than good, or why some proteins lose their function by increase interactions with glyco- and lipo-oxidation mediates in the cells (carbonyl stress). Nonetheless, pursue of healthy aging has led the use of antioxidants as a means to disrupt age-associated physiological dysfunctions, dysregulated metabolic processes or prevention of many age-related diseases. Although it is still early to define their exact clinical benefits for treating age-related disease, a diet rich in polyphenolic or other forms of antioxidants does seem to offer hope in delaying the onset of age-related disorders. It is now clear that any deficiency in antioxidant vitamins, inadequate enzymatic antioxidant defenses can distinctive for many age-related disease, and protein carbonylation can used as an indicator of oxidative stress associated diseases and aging status. This review examines antioxidant compounds and plant polyphenols as redox regulators in health, disease and aging processes with hope that a better understanding of the many mechanisms involved with these distinct compounds, which may lead to better health and novel treatment approaches for age-related diseases. PMID:24124633

  16. Age-dependent changes in the sphingolipid composition of CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sphingolipid (SL4) composition can influence the biophysical properties of cell membranes. Additionally, specific SL modulate signaling pathways involved in proliferation, senescence, and apoptosis. We investigated age-dependent changes in the SL composition of CD4+ T cells, and the impact of these ...

  17. Age-dependent impacts of peatland restoration on the net ecosystem CO2 exchange of blanket bogs in Northern Scotland

    NASA Astrophysics Data System (ADS)

    Hambley, Graham; Hill, Timothy; Saunders, Matthew; Arn Teh, Yit

    2015-04-01

    The Flow Country of Northern Scotland is the largest area of contiguous blanket bog in the UK covering an area in excess of 400 km2. This region is the single largest peat and soil C repository in the UK, and plays a key role in mediating regional atmospheric exchanges of greenhouse gases (GHGs) such as carbon dioxide (CO2), methane (CH4) and water vapour (H2O). However, these peatlands were subject to significant afforestation in the 1980s, where large areas of blanket bog were drained and planted with Sitka spruce (Picea sitchensis) and Lodgepole Pine (Pinus contorta), resulting in modifications to micro-topographic features, vegetation composition and soil properties such as bulk density and water holding capacity, all of which are known to influence the production and emission of key GHGs. Since the late 1990s restoration work has been undertaken to remove forest plantations and to restore the peatland areas by raising the water table, predominantly by drain and furrow blocking, in order to encourage the recolonisation of Sphagnum species. Here we report findings from an eddy covariance study of CO2 and H2O exchange from an unmanaged peatland and a chronosequence of restored peatland sites, which were felled in 1998 and 2004. Located within the Forsinard Flows National Nature Reserve in Northern Scotland, these sites are being studied to better understand the key drivers of carbon dynamics in these ecosystems and also assess the age-dependent impacts of peatland restoration on the net CO2 sink strength. Preliminary data show rates of CO2 uptake increased with time since restoration, with peak assimilation rates of -9.9 and -14.4 micro mol CO2 m-2 s-1 measured at the 10 and 16 year old restoration sites, respectively. Carbon losses through ecosystem respiration followed a similar pattern. The data collected to date indicates that while peatland restoration is actively increasing CO2 uptake at each of the sites, more long-term observational data is required to

  18. Optimization of forest age-dependent light-use efficiency and its implications on climate-vegetation interactions in china

    NASA Astrophysics Data System (ADS)

    Li, Z.; Zhou, T.

    2015-04-01

    Forest's net primary productivity (NPP) is a key index in studying interactions of climate and vegetation, and accurate prediction of NPP is essential to understand the forests' response to climate change. The magnitude and trends of forest NPP not only depend on climate factors (e.g., temperature and precipitation), but also on the succession stages (i.e., forest stand age). Although forest stand age plays a significant role on NPP, it is usually ignored by remote sensing-based models. In this study, we used remote sensing data and meteorological data to estimate forest NPP in China based on CASA model, and then employed field observations to inversely estimate the parameter of maximum light-use efficiency (ɛmax) of forests in different stand ages. We further developed functions to describe the relationship between maximum light-use efficiency (ɛmax) and forest stand age, and estimated forest age-dependent NPP based on these functions. The results showed that ɛmax has changed according to forest types and the forest stand age. For deciduous broadleaf forest, the average ɛmax of young, middle-aged and mature forest are 0.68, 0.65 and 0.60 gC MJ-1. For evergreen broadleaf forest, the average ɛmax of young, middle-aged and mature forests are 1.05, 1.01 and 0.99 gC MJ-1. For evergreen needleleaf forest, the average ɛmax of young, middle-aged and mature forests are 0.72, 0.57 and 0.52 gC MJ-1.The NPP of young and middle-aged forests were underestimated based on a constant ɛmax. Young forests and middle-aged forests had higher ɛmax, and they were more sensitive to trends and fluctuations of climate change, so they led to greater annual fluctuations of NPP. These findings confirm the importance of considering forest stand age to the estimation of NPP and they are significant to study the response of forests to climate change.

  19. Simultaneous age-dependent and age-independent sexual selection in the lekking black grouse (Lyrurus tetrix).

    PubMed

    Kervinen, Matti; Lebigre, Christophe; Soulsbury, Carl D

    2016-05-01

    Individuals' reproductive success is often strongly associated with their age, with typical patterns of early-life reproductive improvement and late-life senescence. These age-related patterns are due to the inherent trade-offs between life-history traits competing for a limited amount of resources available to the organisms. In males, such trade-offs are exacerbated by the resource requirements associated with the expression of costly sexual traits, leading to dynamic changes in trait expression throughout their life span. Due to the age dependency of male phenotypes, the relationship between the expression of male traits and mating success can also vary with male age. Hence, using longitudinal data in a lekking species with strong sexual selection - the black grouse Lyrurus tetrix - we quantified the effects of age, life span and age of first lek attendance (AFL) on male annual mating success (AMS) to separate the effects of within-individual improvement and senescence on AMS from selective (dis)appearance of certain phenotypes. Then, we used male AMS to quantify univariate and multivariate sexual selection gradients on male morphological and behavioural traits with and without accounting for age and age-related effects of other traits. Male AMS increased with age, and there was no significant reproductive senescence. Most males never copulated, and of the ones that did, the majority had only one successful year. Life span was unrelated to AMS, but early AFL tended to lead to higher AMS at ages 1-3. AMS was related to most morphological and behavioural traits when male age was ignored. Accounting for age and age-specific trait effects (i.e. the interaction between a trait and age) reduced the magnitude of the selection gradients and revealed that behavioural traits are under consistent sexual selection, while sexual selection on morphological traits is stronger in old males. Therefore, sexual selection in black grouse operates primarily on male behaviour and

  20. Age-dependent inhalation doses to members of the public from indoor short-lived radon progeny.

    PubMed

    Brudecki, K; Li, W B; Meisenberg, O; Tschiersch, J; Hoeschen, C; Oeh, U

    2014-08-01

    The main contribution of radiation dose to the human lungs from natural exposure originates from short-lived radon progeny. In the present work, the inhalation doses from indoor short-lived radon progeny, i.e., (218)Po, (214)Pb, (214)Bi, and (214)Po, to different age groups of members of the public were calculated. In the calculations, the age-dependent systemic biokinetic models of polonium, bismuth, and lead published by the International Commission on Radiological Protection (ICRP) were adopted. In addition, the ICRP human respiratory tract and gastrointestinal tract models were applied to determine the deposition fractions in different regions of the lungs during inhalation and exhalation, and the absorption fractions of radon progeny in the alimentary tract. Based on the calculated contribution of each progeny to equivalent dose and effective dose, the dose conversion factor was estimated, taking into account the unattached fraction of aerosols, attached aerosols in the nucleation, accumulation and coarse modes, and the potential alpha energy concentration fraction in indoor air. It turned out that for each progeny, the equivalent doses to extrathoracic airways and the lungs are greater than those to other organs. The contribution of (214)Po to effective dose is much smaller compared to that of the other short-lived radon progeny and can thus be neglected in the dose assessment. In fact, 90 % of the effective dose from short-lived radon progeny arises from (214)Pb and (214)Bi, while the rest is from (218)Po. The dose conversion factors obtained in the present study are 17 and 18 mSv per working level month (WLM) for adult female and male, respectively. This compares to values ranging from 6 to 20 mSv WLM(-1) calculated by other investigators. The dose coefficients of each radon progeny calculated in the present study can be used to estimate the radiation doses for the population, especially for small children and women, in specific regions of the world

  1. Simultaneous age-dependent and age-independent sexual selection in the lekking black grouse (Lyrurus tetrix).

    PubMed

    Kervinen, Matti; Lebigre, Christophe; Soulsbury, Carl D

    2016-05-01

    Individuals' reproductive success is often strongly associated with their age, with typical patterns of early-life reproductive improvement and late-life senescence. These age-related patterns are due to the inherent trade-offs between life-history traits competing for a limited amount of resources available to the organisms. In males, such trade-offs are exacerbated by the resource requirements associated with the expression of costly sexual traits, leading to dynamic changes in trait expression throughout their life span. Due to the age dependency of male phenotypes, the relationship between the expression of male traits and mating success can also vary with male age. Hence, using longitudinal data in a lekking species with strong sexual selection - the black grouse Lyrurus tetrix - we quantified the effects of age, life span and age of first lek attendance (AFL) on male annual mating success (AMS) to separate the effects of within-individual improvement and senescence on AMS from selective (dis)appearance of certain phenotypes. Then, we used male AMS to quantify univariate and multivariate sexual selection gradients on male morphological and behavioural traits with and without accounting for age and age-related effects of other traits. Male AMS increased with age, and there was no significant reproductive senescence. Most males never copulated, and of the ones that did, the majority had only one successful year. Life span was unrelated to AMS, but early AFL tended to lead to higher AMS at ages 1-3. AMS was related to most morphological and behavioural traits when male age was ignored. Accounting for age and age-specific trait effects (i.e. the interaction between a trait and age) reduced the magnitude of the selection gradients and revealed that behavioural traits are under consistent sexual selection, while sexual selection on morphological traits is stronger in old males. Therefore, sexual selection in black grouse operates primarily on male behaviour and

  2. Age-dependent role for Ras-GRF1 in the late stages of adult neurogenesis in the dentate gyrus.

    PubMed

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-03-01

    The dentate gyrus of the hippocampus plays a pivotal role in pattern separation, a process required for the behavioral task of contextual discrimination. One unique feature of the dentate gyrus that contributes to pattern separation is adult neurogenesis, where newly born neurons play a distinct role in neuronal circuitry. Moreover,the function of neurogenesis in this brain region differs in adolescent and adult mice. The signaling mechanisms that differentially regulate the distinct steps of adult neurogenesis in adolescence and adulthood remain poorly understood. We used mice lacking RASGRF1(GRF1), a calcium-dependent exchange factor that regulates synaptic plasticity and participates in contextual discrimination performed by mice, to test whether GRF1 plays a role in adult neurogenesis.We show Grf1 knockout mice begin to display a defect in neurogenesis at the onset of adulthood (~2 months of age), when wild-type mice first acquire the ability to distinguish between closely related contexts. At this age, young hippocampal neurons in Grf1 knockout mice display severely reduced dendritic arborization. By 3 months of age, new neuron survival is also impaired. BrdU labeling of new neurons in 2-month-old Grf1 knockout mice shows they begin to display reduced survival between 2 and 3 weeks after birth, just as new neurons begin to develop complex dendritic morphology and transition into using glutamatergic excitatory input. Interestingly, GRF1 expression appears in new neurons at the developmental stage when GRF1 loss begins to effect neuronal function. In addition, we induced a similar loss of new hippocampal neurons by knocking down expression of GRF1 solely in new neurons by injecting retrovirus that express shRNA against GRF1 into the dentate gyrus. Together, these findings show that GRF1 expressed in new neurons promotes late stages of adult neurogenesis. Overall our findings show GRF1 to be an age-dependent regulator of adult hippocampal neurogenesis, which

  3. Refinements on the age-dependent half-life model for estimating child body burdens of polychlorodibenzodioxins and dibenzofurans.

    PubMed

    Kerger, Brent D; Leung, Hon-Wing; Scott, Paul K; Paustenbach, Dennis J

    2007-04-01

    We modified our prior age-dependent half-life model to characterize the range of child (ages 0-7) body burdens associated with dietary and environmental exposure to polychlorodibenzodioxins and furans (PCDD/Fs). Several exposure scenarios were evaluated. Infants were assumed to be either breast-fed or formula-fed from birth to 6 months of age. They then received intakes of PCDD/Fs through age 7 from foods based on weighted means estimates [JECFA, 2001. Joint FAO/WHO Committee on Food Additives. Fifty-seventh meeting, Rome, June 5-14 , 2001, pp. 24-40], and with or without exposures (ingestion and dermal) to urban residential soils at 1ppb TCDD toxic equivalents (TEQ). A one-compartment (adipose volume) toxicokinetic model for TCDD described by Kreuzer [Kreuzer, P.F., Csanady, Gy.A., et al., 1997. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition. Arch. Toxicol. 71, 383-400] was expanded to include the key non-TCDD congeners in human breast milk and adipose tissues, and two model parameter refinements were examined: (1) use of updated and more detailed age-correlated body fat mass data [CDC, 2000. Centers for Disease Control. CDC Growth Charts: United States. Advance Data from Vital and Health Statistics of the Centers for Disease Control and Prevention, National Center for Health Statistics, Number 314, December 2000]; (2) use of breast milk PCDD/F concentration data from sampling completed in 2000-2003 [Wittsiepe, J., Fürst, P., et al., 2004. PCDD/F and dioxin-like PCB in human blood and milk from German mothers. Organohalogen Compd. 66, 2865-2872]. The updated body fat mass data nearly halved the predicted peak body burden for breast-feeding and lowered the time-weighted average (TWA) body burdens from ages 0-7 by 30-40% for breast-fed and formula-fed infants. Combined use of the updated breast milk PCDD/F concentration and body fat

  4. Integrated production of superconductor insulation for chemical vapor deposition of nickel carbonyl

    SciTech Connect

    Snyder, T.S.; Stoltz, R.A.; Wagner, G.R.

    1991-06-04

    This paper describes a process for use in fabrication of nickel suboxide insulation on a superconductor. It comprises: reacting essentially oxygen-free nickel powder with essentially oxygen-free carbon monoxide at a temperature of at least 50{degrees} C. to produce a nickel carbonyl; separating the nickel carbonyl from reaction by-products and excess reagents by cooling the carbonyl to 10{degrees}-43{degrees} C and decanting the nickel carbonyl liquor to produce a purified carbonyl; and at least periodically contacting the purified carbonyl to a surface of a wire containing superconductor or superconductor precursors in an atmosphere at least periodically containing a controlled amount of oxygen, with the wire being at a temperature of 50{degrees}-800{degrees}C to produce nickel suboxide insulation on the wire.

  5. Levels, sources, and health risks of carbonyls in residential indoor air in Hangzhou, China.

    PubMed

    Weng, Mili; Zhu, Lizhong; Yang, Kun; Chen, Shuguang

    2010-04-01

    Concentrations of formaldehyde, acetaldehyde, acetone, propionaldehyde, i-pentanal, and butyraldehyde in residential indoor air in Hangzhou were determined. The mean concentration of the total carbonyl compounds in summer was 222.6 microg/m(3), higher than that in winter (68.5 microg/m(3)). The concentration of a specific carbonyl in indoor air was higher than the outdoor air measurement, indicating the release of carbonyls from the indoor sources. Formaldehyde and acetone were the most abundant carbonyls detected in summer and winter, respectively. Multiple regression analysis indicated that carbonyl concentrations in residential indoor air depended on the age of decoration and furniture, as well as their concentrations in outdoor air. In addition, a primary estimation showed that the health risks of carbonyls in summer were higher than those in winter.

  6. The age dependence of T2 relaxation times of N-acetyl aspartate, creatine and choline in the human brain at 3 and 4T.

    PubMed

    Jiru, F; Skoch, A; Wagnerova, D; Dezortova, M; Viskova, J; Profant, O; Syka, J; Hajek, M

    2016-03-01

    Knowledge of the T2 age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T2 values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T2 values of N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (TE = 30-540 ms, 9 young and 11 elderly subjects) and 4T (TE = 10-180 ms, 18 young and 14 elderly subjects) using single-voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion-recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different TE range. Individual estimated T2 values were statistically analyzed using the R programming language for the age dependence of T2 values as well as the influence of the MM baseline handling. A significant decrease of T2 values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T2 values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T2 values, we confirmed the age dependence of T2 values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26752593

  7. Analysis of the uncertainties associated with the age-dependent thyroid doses and risk of thyroid cancer due to exposure to {sup 131}I

    SciTech Connect

    Hoffman, F.O.; Apostoaei, A.I.; Nair, S.K.

    1996-06-01

    Effects on the thyroid gland due to exposure to {sup 131}I are currently of interest for ongoing retrospective studies of historical releases in Oak Ridge, Tennessee, and Hanford, Washington. Most of the work to date has been limited to dose estimation. This work focuses on estimating both dose and risk of thyroid cancer to an exposed individual. The age-dependent thyroid dose is calculated using a standard metabolic model for iodine. Updated information on thyroid mass from measurements using modem ultrasound techniques was used. The age-dependent risk is calculated using a linear excess relative risk model. An analysis of uncertainties in dose and risk estimates was performed for an individual in a population characterized by the mass of thyroid, by the iodine metabolic parameters, by the background incidence of thyroid cancer and by the excess relative risk per Gy of absorbed dose. The uncertainty analysis was performed using Monte-Carlo simulation, by considering the age-dependent parameters as random functions. The correlation between the metabolic age-dependent parameters was considered explicitly. Special attention is given to a modifying factor that accounts for the effectiveness of {sup 131}I in inducing thyroid cancer as compared to gamma irradiation, for which most of the excess risk factors are derived. This factor is based on review of recent literature and on informal interviews with outside experts, and thus, the expressed uncertainty is subjective in nature. The paper summarizes the age-dependent dose conversion factors (Sv Bq{sup -1}) and slope factors (risk Bq{sup -1}) as well as the uncertainty associated with them. An analysis that identifies the parameters of dominant importance by their contributions to the overall uncertainty is also included.

  8. Selective transformation of carbonyl ligands to organic molecules

    SciTech Connect

    Cutler, A.R.

    1992-05-12

    Studies on the carbonylation of ({eta}{sup 5}-indenyl)(L)(CO)Ru-R complexes (L = CO, PPh{sub 3}; R = CH{sub 2}OMe, CH{sub 3}) have been completed. Particularly noteworthy is that the methoxymethyl complexes readily transform to their acyl derivatives under mild conditions that leave their iron congeners inert towards CO. Surprisingly, even ({eta}{sup 5}-indenyl)(PPh{sub 3}){sub 2}Ru-CH{sub 3} carbonylates and gives ({eta}{sup 5}-indenyl)(PPh{sub 3})(CO)Ru-C(O)CH{sub 3}. Mechanistic studies on the non catalyzed'' hydrosilation of the manganese acyls (CO){sub 5}Mn-C(O)CH{sub 2}R (R = H, OCH{sub 3}, CH{sub 3}) with Et{sub 3}SiH and of cobalt acetyls (CO){sub 3}(PR{sub 3})CoC(O)CH{sub 3} with several monohydrosilanes have been completed. The cobalt acetyls cleanly give ethoxysilanes (not acetaldehyde), and the manganese acyls provide {alpha}-siloxyvinyl complexes Z-(CO){sub 5}Mn-C(OSiEt{sub 3})=CHR (R = H, CH{sub 3}, OCH{sub 3}). Carbonylation and protolytic cleavage of the latter generate pyruvoyl complexes (CO){sub 5}Mn-COCOR (R = CH{sub 3}, CH{sub 2}CH{sub 3}), formally the products of net double carbonylation'' sequences. Studies in progress are concerned with how manganese complexes as diverse as (CO){sub 5}Mn-Y (Y = C(O)R, R, BR - but not SiMe{sub 3} or Mn(CO){sub 5}) and ({eta}{sup 3}-C{sub 3}H{sub 5})Mn(CO){sub 2}L (but not CpMn(CO){sub 3} or CpMn(CO){sub 2}({eta}{sup 2}HSiR{sub 3})) function as efficient hydrosilation catalysts towards Cp(CO){sub 2}FeC(O)CH{sub 3}, for example. These reactions cleanly afford fully characterized {alpha}-siloxyethyl complexes Fp-CH(OSiR{sub 3})CH{sub 3} under conditions where typically Rh(1) hydrosilation catalysts are inactive. Several of these manganese complexes also catalytically hydrosilate organic esters, including lactones, to their ethers R-CH{sub 2}OR; these novel ester reductions occur quantitatively at room temperature and appear to be general in scope.

  9. Palladium-Catalyzed Regioselective Difluoroalkylation and Carbonylation of Alkynes.

    PubMed

    Wang, Qiang; He, Yu-Tao; Zhao, Jia-Hui; Qiu, Yi-Feng; Zheng, Lan; Hu, Jing-Yuan; Yang, Yu-Chen; Liu, Xue-Yuan; Liang, Yong-Min

    2016-06-01

    A novel, four-component synthetic strategy to synthesize a series of β-difluoroalkyl unsaturated esters/amides with high regioslectivity is described. This Pd-catalyzed difluoroalkylation and carbonylation reaction can be carried out with simple starting materials. Through this protocol, two new C-C bonds (including one C-CF2 bond) and one C-O(N) bond are constructed simultaneously in a single step. The synthetic utility of this reaction system has been certified by the applicability to a wide scope of alkynes and nucleophiles. Preliminary mechanistic studies suggest that the difluoroalkyl radical pathway is involved in this reaction. PMID:27191858

  10. AGE-DEPENDENT EFFECTS OF AROCLOR 1254 ON CALCIUM UPTAKE BY SUBCELLULAR ORGANELLES IN SELECTED BRAIN REGIONS OF RATS.

    EPA Science Inventory

    Earlier reports from our laboratory have indicated that polychlorinated biphenyls (PCBs) affect signal transduction mechanisms in brain, including Ca2+ homeostasis, phosphoinositol hydrolysis, and protein kinase C (PKC) translocation in mature neurons and adult brain homogenate p...

  11. Levels and health risks of carbonyl compounds in selected public places in Hangzhou, China.

    PubMed

    Weng, Mili; Zhu, Lizhong; Yang, Kun; Chen, Shuguang

    2009-05-30

    The concentrations of six carbonyl compounds in indoor air were measured for selected public places in Hangzhou, including shopping centers, supermarkets, furniture store, inter-city bus stations, railway stations and cinemas. In indoor air of the public places, the mean concentration was 146.5 microg/m(3) for total carbonyls, in which formaldehyde was found to be the most abundant carbonyls with an average value of 90.6 microg/m(3) and followed by acetone and acetaldehyde. Among the selected public places, the furniture store presented the highest carbonyl concentrations in the indoor air, followed by shopping centers, supermarkets, cinemas, while the railway stations and inter-city bus stations presented relatively lower carbonyl concentrations. Carbonyl concentrations in indoor air for the different areas of shopping centers and supermarkets were also investigated. The results showed that the highest carbonyl concentrations were found in restaurant and bedclothes areas for shopping centers and in the cooked food areas for supermarkets. The average ratios of the indoor/outdoor (I/O) for carbonyl concentrations were greater than 1, which indicated that the indoor sources significantly contributed to carbonyls, such as indoor materials and anthropogenic activities. Preliminary estimate of the health risk for staffs, customers and passengers in public places was discussed.

  12. Borane-Catalyzed Reductive α-Silylation of Conjugated Esters and Amides Leaving Carbonyl Groups Intact.

    PubMed

    Kim, Youngchan; Chang, Sukbok

    2016-01-01

    Described herein is the development of the B(C6F5)3-catalyzed hydrosilylation of α,β-unsaturated esters and amides to afford synthetically valuable α-silyl carbonyl products. The α-silylation occurs chemoselectively, thus leaving the labile carbonyl groups intact. The reaction features a broad scope of both acyclic and cyclic substrates, and the synthetic utility of the obtained α-silyl carbonyl products is also demonstrated. Mechanistic studies revealed two operative steps: fast 1,4-hydrosilylation of conjugated carbonyls and then slow silyl group migration of a silyl ether intermediate. PMID:26549843

  13. Deuterium enrichment by selective photo-induced dissociation of an organic carbonyl compound

    DOEpatents

    Marling, John B.

    1981-01-01

    A method for producing a deuterium enriched material by photoinduced dissociation which uses as the working material a gas phase photolytically dissociable organic carbonyl compound containing at least one hydrogen atom bonded to an atom which is adjacent to a carbonyl group and consisting of molecules wherein said hydrogen atom is present as deuterium and molecules wherein said hydrogen atom is present as another isotope of hydrogen. The organic carbonyl compound is subjected to intense infrared radiation at a preselected wavelength to selectively excite and thereby induce dissociation of the deuterium containing species to yield a deuterium enriched stable molecular product. Undissociated carbonyl compound, depleted in deuterium, is preferably redeuterated for reuse.

  14. Age dependency of the metabolic conversion of polyamines into amino acids in IMR-90 human embryonic lung diploid fibroblasts

    SciTech Connect

    Chen, K.Y.; Chang, Z.

    1986-07-01

    When radioactive polyamines (putrescine or spermidine) were incubated with mammalian cells in tissue culture, the radioactivity was incorporated into cellular proteins via two different metabolic pathways; one is metabolic labeling of an 18,000-dalton protein via hypusine formation, and the other is general protein synthesis employing radioactive amino acids derived from biodegradation of polyamines via GABA shunt and Krebs cycle. Aminoguanidine, a potent inhibitor of diamine oxidase, blocked the metabolic conversion of polyamines to amino acids but had no effect on the metabolic labeling of the 18,000-dalton protein. The authors have investigated these two polyamine-associated biochemical events in IMR-90 human diploid fibroblasts as a function of their population doubling level (PDL). They found that (1) the metabolic labeling of the 18,000-dalton protein was about two-fold greater in young cells (PDL = 22) than that in old cells (PDL = 48), and (2) the metabolic labeling of other cellular proteins, employing amino acids derived from putrescine via polyamine catabolic pathway, was more than six-fold greater in the old cells (PDL = 48) than in the young cells (PDL = 22). Since the rate of protein synthesis was about 1.4-fold higher in the young cells as compared to the old cells, their data indicated that the activity of catabolic conversion of putrescine (or spermidine) to amino acids in old IMR-90 cells was about eight-fold greater than that in young cells. This remarkable increase of polyamine catabolism and the slight decrease of metabolic labeling of the 18,000-dalton protein were also observed in cell strains derived from patients with premature aging disease.

  15. Development of a photolabile carbonyl-protecting group toolbox.

    PubMed

    Yang, Haishen; Zhang, Xin; Zhou, Lei; Wang, Pengfei

    2011-04-01

    New salicyl alcohol derived photolabile carbonyl protecting groups have been developed, and the effect of substituents on the photochemical properties of photolabile protecting groups (PPGs) has been studied. The 3-(dimethylamino)phenyl groups at the α position prove to be important to the efficiency of the deprotection reactions, as shown in the photo reactions of the acetal 9. On the other hand, expansion of the salicyl alcohol's benzene skeleton to naphthalene does not improve the photochemical properties of PPGs. A neutral protecting protocol has been generalized to new PPGs with α,α-diaryl salicyl alcohol backbone. Thus, installation of PPGs onto aldehydes is readily achieved at 140 °C without using any other chemical reagents. These PPGs are stable under acidic conditions typical for hydrolyzing acetals and constitute orthogonal protecting groups with traditional 1,3-dioxane/1,3-dioxolane for carbonyl compounds. Highly efficient release of carbohydrate molecules is demonstrated, which can be potentially useful in site-specific release and immobilization of carbohydrates for preparation of high-density microarrays. With the enriched PPG toolbox, PPGs are divided into three subgroups based on their UV absorption profiles. PPGs from different subgroups can be sequentially removed by using different UV irradiation wavelengths. For PPGs absorbing UVA (λ >315 nm), photochemical deprotection can be carried out with sunlight in high yields. PMID:21370916

  16. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats

    PubMed Central

    Aldini, Giancarlo; Orioli, Marica; Rossoni, Giuseppe; Savi, Federica; Braidotti, Paola; Vistoli, Giulio; Yeum, Kyung-Jin; Negrisoli, Gianpaolo; Carini, Marina

    2011-01-01

    Abstract The metabolic syndrome is a risk factor that increases the risk for development of renal and vascular complications. This study addresses the effects of chronic administration of the endogenous dipeptide carnosine (β-alanyl-L-histidine, L-CAR) and of its enantiomer (β-alanyl-D-histidine, D-CAR) on hyperlipidaemia, hypertension, advanced glycation end products, advanced lipoxidation end products formation and development of nephropathy in the non-diabetic, Zucker obese rat. The Zucker rats received a daily dose of L-CAR or D-CAR (30 mg/kg in drinking water) for 24 weeks. Systolic blood pressure was recorded monthly. At the end of the treatment, plasma levels of triglycerides, total cholesterol, glucose, insulin, creatinine and urinary levels of total protein, albumin and creatinine were measured. Several indices of oxidative/carbonyl stress were also measured in plasma, urine and renal tissue. We found that both L- and D-CAR greatly reduced obese-related diseases in obese Zucker rat, by significantly restraining the development of dyslipidaemia, hypertension and renal injury, as demonstrated by both urinary parameters and electron microscopy examinations of renal tissue. Because the protective effect elicited by L- and D-CAR was almost superimposable, we conclude that the pharmacological action of L-CAR is not due to a pro-histaminic effect (D-CAR is not a precursor of histidine, since it is stable to peptidic hydrolysis), and prompted us to propose that some of the biological effects can be mediated by a direct carbonyl quenching mechanism. PMID:20518851

  17. Transition-metal-catalyzed carbonylation reactions of olefins and alkynes: a personal account.

    PubMed

    Wu, Xiao-Feng; Fang, Xianjie; Wu, Lipeng; Jackstell, Ralf; Neumann, Helfried; Beller, Matthias

    2014-04-15

    Carbon monoxide was discovered and identified in the 18th century. Since the first applications in industry 80 years ago, academic and industrial laboratories have broadly explored CO's use in chemical reactions. Today organic chemists routinely employ CO in organic chemistry to synthesize all kinds of carbonyl compounds. Despite all these achievements and a century of carbonylation catalysis, many important research questions and challenges remain. Notably, apart from academic developments, industry applies carbonylation reactions with CO on bulk scale. In fact, today the largest applications of homogeneous catalysis (regarding scale) are carbonylation reactions, especially hydroformylations. In addition, the vast majority of acetic acid is produced via carbonylation of methanol (Monsanto or Cativa process). The carbonylation of olefins/alkynes with nucleophiles, such as alcohols and amines, represent another important type of such reactions. In this Account, we discuss our work on various carbonylations of unsaturated compounds and related reactions. Rhodium-catalyzed isomerization and hydroformylation reactions of internal olefins provide straightforward access to higher value aldehydes. Catalytic hydroaminomethylations offer an ideal way to synthesize substituted amines and even heterocycles directly. More recently, our group has also developed so-called alternative metal catalysts based on iridium, ruthenium, and iron.