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Sample records for age-dependent protein carbonylation

  1. 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

  2. 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

  3. 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

  4. 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 ...

  5. The role of heat shock protein 70 in mediating age-dependent mortality in sepsis.

    PubMed

    McConnell, Kevin W; Fox, Amy C; Clark, Andrew T; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A; Farris, Alton B; Buchman, Timothy G; Hunt, Clayton R; Coopersmith, Craig M

    2011-03-15

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70(-/-) and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70(-/-) and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70(-/-) mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70(-/-) mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70(-/-) mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977

  6. Age-dependent T cell tolerance and autoimmunity to myelin basic protein.

    PubMed

    Huseby, E S; Sather, B; Huseby, P G; Goverman, J

    2001-04-01

    Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is induced by activating a subset of myelin basic protein (MBP)-specific T cells that have escaped tolerance induction. Here, we define the tolerance mechanisms that eliminate the majority of MBP-specific T cells from the periphery. We show that MBP-specific T cells undergo central tolerance mediated by bone marrow-derived antigen-presenting cells presenting exogenously derived MBP epitopes. The efficiency of tolerance is age dependent, reflecting the developmentally regulated expression of MBP. Dependence of tolerance on the amount of MBP expressed in vivo results in an age window of susceptibility to EAE in mice that peaks during puberty. These results suggest that factors regulating expression of self-antigens in vivo can influence susceptibility to autoimmunity. PMID:11336692

  7. [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

  8. Tissue- and age-dependent expression of the bovine DEFB103 gene and protein.

    PubMed

    Mirabzadeh-Ardakani, Ali; Solie, Jay; Gonzalez-Cano, Patricia; Schmutz, Sheila M; Griebel, Philip J

    2016-02-01

    Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defensin family and in other species DEFB103 protein has diverse functions, including antimicrobial activity, a chemoattractant for dendritic cells, enhancing epithelial wound repair and regulating hair colour. Expression of the bovine DEFB103 gene was surveyed in 27 tissues and transcript was most abundant in tissues with stratified squamous epithelium. Oral cavity epithelial tissues and nictitating membrane consistently expressed high levels of DEFB103 gene transcript. An age-dependent decrease (P < 0.05) in DEFB103 gene expression was only observed for buccal epithelium when comparing healthy 10- to 14-day-old and 10- to 12-month-old calves. A bovine herpesvirus-1 respiratory infection did, however, significantly (P < 0.05) up-regulate DEFB103 gene expression in the buccal epithelium of 6- to 8-month-old calves. Finally, DEFB103 transcript was low in lymph nodes draining the skin and at the limit of detection in other internal organs such as lung, intestine and kidney. Affinity-purified rabbit antisera to bovine DEFB103 was used to identify cells expressing DEFB103 protein within tissues with stratified squamous epitheliums. DEFB103 protein was most abundant in basal epithelial cells and was present in these cells prior to birth. Beta-defensins have been identified as regulators of dendritic cell (DC) chemokine responses and we observed a close association between DCs and epithelial cells expressing DEFB103 in both the fetus and newborn calf. In conclusion, bovine DEFB103 gene expression is most abundant in stratified squamous epithelium with DEFB103 protein localised to basal epithelial cells. These observations are consistent with proposed roles for DEFB103 in DC recruitment and repair of stratified squamous epithelium. PMID:26299200

  9. Cytokinin inhibits the proteasome-mediated degradation of carbonylated proteins in Arabidopsis leaves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Under normal conditions, plants contain numerous carbonylated proteins, which are thought to be indicative of oxidative stress damage. Conditions that promote formation of reactive oxygen species (ROS) enhance protein carbonylation, and protein degradation is required to reverse the damage. However,...

  10. [Assessment of the concentrations of carbonylated proteins and carbonyl reductase enzyme in mexican women with breast cancer: A pilot study].

    PubMed

    Gutiérrez-Salinas, José; García-Ortiz, Liliana; Mondragón-Terán, Paul; Hernández-Rodríguez, Sergio; Ramírez-García, Sotero; Núñez-Ramos, Norma Rebeca

    2016-01-01

    Oxidative stress could promote the development of cancer and implicate carbonylated proteins in the carcinogenic process. The goal of this study was to assess the concentrations of carbonylated proteins and carbonyl reductase enzyme in women with breast cancer and determine whether these markers were possible indicators of tissue damage caused by the disease. A total of 120 healthy women and 123 women with a diagnosis of breast cancer were included. The concentration of carbonylated proteins in plasma and the concentration of carbonyl reductase enzyme in leukocytes were determined using the ELISA assay. There was a 3.76-fold increase in the amount of carbonylated proteins in the plasma from the patient group compared with healthy control group (5±3.27 vs. 1.33±2.31 nmol carbonyls/mg protein; p<0.05). Additionally, a 60% increase in the carbonyl reductase enzyme was observed in the patient group compared with the healthy control group (3.27±0.124 vs. 2.04±0.11 ng/mg protein; p<0.05). A positive correlation (r=0.95; p<0.001) was found between both measurements. These results suggest the presence of tissue damage produced by cancer; therefore, these parameters could be used to indicate tissue damage in cancer patients. PMID:26927639

  11. 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

  12. 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.

  13. 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

  14. [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

  15. 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. PMID:25943699

  16. Nature of Amide Carbonyl−Carbonyl Interactions in Proteins

    PubMed Central

    2010-01-01

    Noncovalent interactions define and modulate biomolecular structure, function, and dynamics. In many protein secondary structures, an intimate interaction exists between adjacent carbonyl groups of the main-chain amide bonds. As this short contact contributes to the energetics of protein conformational stability as well as protein−ligand interactions, understanding its nature is crucial. The intimacy of the carbonyl groups could arise from a charge−charge or dipole−dipole interaction, or n→π * electronic delocalization. This last putative origin, which is reminiscent of the Bürgi−Dunitz trajectory, involves delocalization of the lone pairs (n) of the oxygen (Oi−1) of a peptide bond over the antibonding orbital (π*) of the carbonyl group (Ci=Oi) of the subsequent peptide bond. By installing isosteric chemical substituents in a peptidic model system and using NMR spectroscopy, X-ray diffraction analysis, and ab initio calculations to analyze the consequences, the intimate interaction between adjacent carbonyl groups is shown to arise primarily from n→π* electronic delocalization. This finding has implications for organic, biological, and medicinal chemistry. PMID:19469574

  17. Fluorimetric screening assay for protein carbonyl evaluation in biological samples.

    PubMed

    Stocker, P; Ricquebourg, E; Vidal, N; Villard, C; Lafitte, D; Sellami, L; Pietri, S

    2015-08-01

    Many assays are available for the detection of protein carbonyls (PCs). Currently, the measurement of PC groups after their derivatization with 2,4-dinitrophenol hydrazine (DNPH) is widely used for measuring protein oxidation in biological samples. However, this method includes several washing steps. In this context, we have developed a rapid, sensitive, and accurate fluorimetric method adapted to 96-well microplates for the convenient assessment of protein carbonyl level in biological samples. The method reported here is based on the reaction of carbonyl content in proteins with 7-hydrazino-4-nitrobenzo-2,1,3-oxadiazole (NBDH) to form highly fluorescent derivatives via hydrazone formation. PCs were determined using the DNPH and NBDH assays in fully reduced bovine serum albumin (BSA) and plasma and liver homogenates obtained from healthy control rats up the addition of various amounts of HOCl-oxidized BSA (OxBSA). Using the NBDH assay, PC concentrations as low as 0.2 nmol/mg were detected with precision as low as 5%. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectroscopy was used to successfully identify the formation of the NBDH adducts after derivatization with standard oxidized peptides. Finally, the two methods were further used for PC determination in plasma and liver samples from diabetic and normal rats, showing that the NBDH assay can be reliably used in biological experiments. PMID:25933703

  18. Protein Carbonylation, Mitochondrial Dysfunction, and Insulin Resistance123

    PubMed Central

    Frohnert, Brigitte I.; Bernlohr, David A.

    2013-01-01

    Oxidative stress has been identified as a common mechanism for cellular damage and dysfunction in a wide variety of disease states. Current understanding of the metabolic changes associated with obesity and the development of insulin resistance has focused on the role of oxidative stress and its interaction with inflammatory processes at both the tissue and organismal level. Obesity-related oxidative stress is an important contributing factor in the development of insulin resistance in the adipocyte as well as the myocyte. Moreover, oxidative stress has been linked to mitochondrial dysfunction, and this is thought to play a role in the metabolic defects associated with oxidative stress. Of the various effects of oxidative stress, protein carbonylation has been identified as a potential mechanism underlying mitochondrial dysfunction. As such, this review focuses on the relationship between protein carbonylation and mitochondrial biology and addresses those features that point to either the causal or casual relationship of lipid peroxidation–induced protein carbonylation as a determining factor in mitochondrial dysfunction. PMID:23493532

  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. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion.

    PubMed

    Zheng, J; Bizzozero, O A

    2010-03-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the scavengers tested, with the exception of hydralazine, prevented protein carbonylation. These findings suggest that the majority of protein-associated carbonyl groups in this oxidative stress paradigm do not derive from stable lipid peroxidation products like malondialdehyde (MDA), acrolein and 4-hydroxynonenal (4-HNE). This conclusion was confirmed by the observation that the amount of MDA-, acrolein- and 4-HNE-protein adducts does not increase upon GSH depletion. Additional studies revealed that the efficacy of hydralazine at preventing carbonylation was due to its ability to reduce oxidative stress, most likely by inhibiting mitochondrial production of superoxide and/or by scavenging lipid free radicals. PMID:20001647

  2. 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. PMID:15101385

  3. Analysis of dynamic protein carbonylation in rice embryo during germination through AP-SWATH.

    PubMed

    Zhang, Hui; He, Dongli; Yu, Jianlan; Li, Ming; Damaris, Rebecca Njeri; Gupta, Ravi; Kim, Sun Tae; Yang, Pingfang

    2016-03-01

    Seed germination is an important aspect of the plant life cycle, during which, reactive oxygen species (ROS) accumulate. The accumulation of ROS results in an increase in protein oxidation of which carbonylation is the most canonical one. However, there is insufficient information concerning protein oxidation, especially carbonylation and its contribution to seed germination. In this study, biotin hydrazide labeled chromatography combined with sequential window acquisition of all theoretical fragment ion spectra (SWATH) method was used to analyze the dynamic pattern of protein carbonylation in rice embryos during germination. A total of 1872 unique proteins were quantified, among which 288 carbonylated peptides corresponding to 144 proteins were determined based on the filtering through mass shifts of modified amino acids. In addition, 66 carbonylated proteins were further analyzed based on their carbonylation intensity in four stages of germination. These identified carbonylated proteins were mainly involved in maintaining the levels of ROS, abscisic acid and seed reserves. Remarkably, a peroxiredoxin was found with 23 unique carbonylated peptides, and the expression of which was consistent with its increased activity. This study describes the dynamic pattern of carbonylated proteins during seed germination, and may help to further understand the biochemical mechanisms on this process. PMID:26801057

  4. Protein carbonylation during natural leaf senescence in winter wheat, as probed by fluorescein-5-thiosemicarbazide.

    PubMed

    Havé, M; Leitao, L; Bagard, M; Castell, J-F; Repellin, A

    2015-09-01

    Leaf senescence is characterised by a massive degradation of proteins in order to recycle nitrogen to other parts of the plant, such as younger leaves or developing grain/seed. Protein degradation during leaf senescence is a highly regulated process and it is suggested that proteins to be degraded are marked by an oxidative modification (carbonylation) that makes them more susceptible to proteolysis. However, there is as yet no evidence of an increase in protein carbonylation level during natural leaf senescence. The aim of our study was thus to monitor protein carbonylation level during the process of natural senescence in the flag leaf of field-grown winter wheat plants. For this purpose, we adapted a fluorescence-based method using fluorescein-5-thiosemicarbazide (FTC) as a probe for detecting protein carbonyl derivatives. As used for the first time on plant material, this method allowed the detection of both quantitative and qualitative modifications in protein carbonyl levels during the last stages of wheat flag leaf development. The method described herein represents a convenient, sensitive and reproducible alternative to the commonly used 2,4-dinitrophenylhydrazine (DNPH)-based method. In addition, our analysis revealed changes in protein carbonylation level during leaf development that were associated with qualitative changes in protein abundance and carbonylation profiles. In the senescing flag leaf, protein carbonylation increased concomitantly with a stimulation of endoproteolytic activity and a decrease in protein content, which supports the suggested relationship between protein oxidation and proteolysis during natural leaf senescence. PMID:25683278

  5. 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. PMID:26706659

  6. 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

  7. Behaviour of protein carbonyl groups in juvenile myocardial infarction.

    PubMed

    Caimi, Gregorio; Canino, Baldassare; Incalcaterra, Egle; Ferrera, Eleonora; Montana, Maria; Lo Presti, Rosalia

    2013-01-01

    Acute myocardial infarction (AMI) is accompanied by oxidative stress, and protein oxidation is among the consequences of oxidative stress. We examined the plasma concentration of protein carbonyl groups (PC), a marker of protein oxidation, in a group of young subjects with AMI (45 men and 5 women; mean age 40.4 ± 4.8 yrs). We found a significant increase of PC (p < 0.001) in comparison with normal controls. No difference was observed between patients with AMI characterized by elevated ST segment and those without elevation of ST segment. There was no correlation between the ejection fraction and PC in the whole group nor in the subgroups of STEMI and non-STEMI patients. Subdividing the whole group of AMI patients according to the number of risk factors and the number of stenosed coronary vessels, the difference in PC level was not statistically significant among the subgroups. This study showed an increased protein oxidation in young subjects with recent AMI. Further investigation is needed to ascertain whether this can be a target of therapeutic intervention. PMID:22504219

  8. 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

  9. AminoxyTMT: A novel multi-functional reagent for characterization of protein carbonylation.

    PubMed

    Afiuni-Zadeh, Somaieh; Rogers, John C; Snovida, Sergei I; Bomgarden, Ryan D; Griffin, Timothy J

    2016-01-01

    Protein carbonylation is a common oxidative stress (OS)-driven post-translational modification (PTM). Proteome-wide carbonylation events can best be characterized using a combination of analytical approaches. Immunoblotting of carbonylated proteins provides data on the extent of modifications within complex samples, as well as a broad comparison of carbonylation profiles between different biological states (e.g., disease versus control), while mass spectrometry (MS)-based analysis provides information on proteins susceptible to carbonylation, as well as the potential for quantitative characterization of specific sites of amino acid modification. Here, we present a novel use for aminoxyTMT, a derivative of the Tandem Mass Tag (TMT) isobaric labeling reagent, which utilizes an aminooxy functional group for covalent labeling of reactive carbonyls in proteins. When coupled with anti-TMT antibody, we demonstrate the use of aminoxyTMT for immunoblot profiling of protein carbonylation in complex mixtures, as well as enrichment of modified peptides from these mixtures. Proof-of-principle experiments also show the amenability of aminoxyTMT-labeled carbonylated peptides enriched from complex mixtures to identification using tandem MS (MS/MS) and database searching, as well as quantitative analysis using TMT-based reporter ion intensity measurements. PMID:27071607

  10. Fluorescence labeling of carbonylated lipids and proteins in cells using coumarin-hydrazide

    PubMed Central

    Vemula, Venukumar; Ni, Zhixu; Fedorova, Maria

    2015-01-01

    Carbonylation is a generic term which refers to reactive carbonyl groups present in biomolecules due to oxidative reactions induced by reactive oxygen species. Carbonylated proteins, lipids and nucleic acids have been intensively studied and often associated with onset or progression of oxidative stress related disorders. In order to reveal underlying carbonylation pathways and biological relevance, it is crucial to study their intracellular formation and spatial distribution. Carbonylated species are usually identified and quantified in cell lysates and body fluids after derivatization using specific chemical probes. However, spatial cellular and tissue distribution have been less often investigated. Here, we report coumarin-hydrazide, a fluorescent chemical probe for time- and cost-efficient labeling of cellular carbonyls followed by fluorescence microscopy to evaluate their intracellular formation both in time and space. The specificity of coumarin-hydrazide was confirmed in time- and dose-dependent experiments using human primary fibroblasts stressed with paraquat and compared with conventional DNPH-based immunocytochemistry. Both techniques stained carbonylated species accumulated in cytoplasm with strong perinuclear clustering. Using a complimentary array of analytical methods specificity of coumarin-hydrazide probe towards both protein- and lipid-bound carbonyls has been shown. Additionally, co-distribution of carbonylated species and oxidized phospholipids was demonstrated. PMID:25974625

  11. 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

  12. Characterization of modified proteins in plasma from a subtype of schizophrenia based on carbonyl stress: Protein carbonyl is a possible biomarker of psychiatric disorders.

    PubMed

    Koike, Shin; Kayama, Tasuku; Arai, Makoto; Horiuchi, Yasue; Kobori, Akiko; Miyashita, Mitsuhiro; Itokawa, Masanari; Ogasawara, Yuki

    2015-11-13

    Although it's well known that protein carbonyl (PCO) and advanced glycation end-products (AGEs) levels are elevated in plasma from patients with renal dysfunction, we recently identified patients who had no renal dysfunction but possessed high levels of plasma pentosidine (PEN), which is an AGEs, and low vitamin B6 levels in serum. In this study, we investigated the status of carbonyl stress to characterize the subtype of schizophrenia. When plasma samples were subjected to Western blot analysis for various AGEs, clear differences were only observed with the anti-PEN antibody in the plasma from schizophrenic patients. Moreover, we determined the formation of protein carbonyl (PCO), a typical indicator of carbonyl stress, occurred prior to the accumulation of PEN in the plasma of schizophrenic patients. PCO levels in the plasma from schizophrenic patients were significantly higher than that from healthy subjects. Western blots analysis clearly showed that albumin and IgG were markedly carbonylated in the plasma of some patients. Thus, PCOs may be a novel marker of carbonyl stress-type schizophrenia in addition to albumin containing PEN structure. PMID:26431870

  13. 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.

  14. 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

  15. Protein carbonylation associated to high-fat, high-sucrose diet and its metabolic effects.

    PubMed

    Méndez, Lucía; Pazos, Manuel; Molinar-Toribio, Eunice; Sánchez-Martos, Vanesa; Gallardo, José M; Rosa Nogués, M; Torres, Josep L; Medina, Isabel

    2014-12-01

    The present research draws a map of the characteristic carbonylation of proteins in rats fed high-caloric diets with the aim of providing a new insight of the pathogenesis of metabolic diseases derived from the high consumption of fat and refined carbohydrates. Protein carbonylation was analyzed in plasma, liver and skeletal muscle of Sprague-Dawley rats fed a high-fat, high-sucrose (HFHS) diet by a proteomics approach based on carbonyl-specific fluorescence-labeling, gel electrophoresis and mass spectrometry. Oxidized proteins along with specific sites of oxidative damage were identified and discussed to illustrate the consequences of protein oxidation. The results indicated that long-term HFHS consumption increased protein oxidation in plasma and liver; meanwhile, protein carbonyls from skeletal muscle did not change. The increment of carbonylation by HFHS diet was singularly selective on specific target proteins: albumin from plasma and liver, and hepatic proteins such as mitochondrial carbamoyl-phosphate synthase (ammonia), mitochondrial aldehyde dehydrogenase, argininosuccinate synthetase, regucalcin, mitochondrial adenosine triphosphate synthase subunit beta, actin cytoplasmic 1 and mitochondrial glutamate dehydrogenase 1. The possible consequences that these specific protein carbonylations have on the excessive weight gain, insulin resistance and nonalcoholic fatty liver disease resulting from HFHS diet consumption are discussed. PMID:25282656

  16. Protein carbonylation and aggregation precede neuronal apoptosis induced by partial glutathione depletion

    PubMed Central

    Dasgupta, Anushka; Zheng, Jianzheng; Bizzozero, Oscar A.

    2012-01-01

    While the build-up of oxidized proteins within cells is believed to be toxic, there is currently no evidence linking protein carbonylation and cell death. In the present study, we show that incubation of nPC12 (neuron-like PC12) cells with 50 μM DEM (diethyl maleate) leads to a partial and transient depletion of glutathione (GSH). Concomitant with GSH disappearance there is increased accumulation of PCOs (protein carbonyls) and cell death (both by necrosis and apoptosis). Immunocytochemical studies also revealed a temporal/spatial relationship between carbonylation and cellular apoptosis. In addition, the extent of all three, PCO accumulation, protein aggregation and cell death, augments if oxidized proteins are not removed by proteasomal degradation. Furthermore, the effectiveness of the carbonyl scavengers hydralazine, histidine hydrazide and methoxylamine at preventing cell death identifies PCOs as the toxic species. Experiments using well-characterized apoptosis inhibitors place protein carbonylation downstream of the mitochondrial transition pore opening and upstream of caspase activation. While the study focused mostly on nPC12 cells, experiments in primary neuronal cultures yielded the same results. The findings are also not restricted to DEM-induced cell death, since a similar relationship between carbonylation and apoptosis was found in staurosporine- and buthionine sulfoximine-treated nPC12 cells. In sum, the above results show for the first time a causal relationship between carbonylation, protein aggregation and apoptosis of neurons undergoing oxidative damage. To the best of our knowledge, this is the first study to place direct (oxidative) protein carbonylation within the apoptotic pathway. PMID:22376187

  17. 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

  18. CarSPred: a computational tool for predicting carbonylation sites of human proteins.

    PubMed

    Lv, Hongqiang; Han, Jiuqiang; Liu, Jun; Zheng, Jiguang; Liu, Ruiling; Zhong, Dexing

    2014-01-01

    Protein carbonylation is one of the most pervasive oxidative stress-induced post-translational modifications (PTMs), which plays a significant role in the etiology and progression of several human diseases. It has been regarded as a biomarker of oxidative stress due to its relatively early formation and stability compared with other oxidative PTMs. Only a subset of proteins is prone to carbonylation and most carbonyl groups are formed from lysine (K), arginine (R), threonine (T) and proline (P) residues. Recent advancements in analysis of the PTM by mass spectrometry provided new insights into the mechanisms of protein carbonylation, such as protein susceptibility and exact modification sites. However, the experimental approaches to identifying carbonylation sites are costly, time-consuming and capable of processing a limited number of proteins, and there is no bioinformatics method or tool devoted to predicting carbonylation sites of human proteins so far. In the paper, a computational method is proposed to identify carbonylation sites of human proteins. The method extracted four kinds of features and combined the minimum Redundancy Maximum Relevance (mRMR) feature selection criterion with weighted support vector machine (WSVM) to achieve total accuracies of 85.72%, 85.95%, 83.92% and 85.72% for K, R, T and P carbonylation site predictions respectively using 10-fold cross-validation. The final optimal feature sets were analysed, the position-specific composition and hydrophobicity environment of flanking residues of modification sites were discussed. In addition, a software tool named CarSPred has been developed to facilitate the application of the method. Datasets and the software involved in the paper are available at https://sourceforge.net/projects/hqlstudio/files/CarSPred-1.0/. PMID:25347395

  19. 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.

  20. Novel DNPH-based method for determination of protein carbonylation in muscle and meat.

    PubMed

    Soglia, Francesca; Petracci, Massimiliano; Ertbjerg, Per

    2016-04-15

    Protein oxidation is considered an ongoing deteriorative process during storage of fresh and processed meat. Carbonyl compounds have traditionally been detected spectrophotometrically after derivatization with 2,4-dinitrophenylhydrazine (DNPH) to form protein-bound hydrazones with absorbance at 370 nm. Here we describe a novel DNPH-based method to quantify protein carbonylation in muscle and meat. The additional steps of the novel method aimed at increasing the protein solubility and inducing protein unfolding before labeling with DNPH. Compared to the traditional method, the new procedure reflected an increased protein carbonylation level measuring overall two to fourfold more carbonyls in muscles from different species as well as in soluble, salt-soluble and insoluble protein fractions. The study suggested that protein unfolding is a more important phenomenon than solubilization for increased DNPH labeling. The novel method resulted in three to fourfold larger carbonyl content determined in chicken, pork and beef (2.8, 3.6 and 3.1 nmol/mg of protein, respectively). PMID:26617002

  1. Dynein Dysfunction Reproduces Age-Dependent Retromer Deficiency: Concomitant Disruption of Retrograde Trafficking Is Required for Alteration in β-Amyloid Precursor Protein Metabolism.

    PubMed

    Kimura, Nobuyuki; Samura, Eriko; Suzuki, Keiko; Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro

    2016-07-01

    It is widely accepted that β-amyloid (Aβ) protein plays a pivotal role in Alzheimer disease pathogenesis, and accumulating evidence suggests that endocytic dysfunction is involved in Aβ pathology. Retromer, a conserved multisubunit complex, mediates the retrograde transport of numerous kinds of cargo from endosomes to the trans-Golgi network. Several studies have found that retromer deficiency enhances Aβ pathology both in vitro and in vivo. Cytoplasmic dynein, a microtubule-based motor protein, mediates minus-end-directed vesicle transport via interactions with dynactin, another microtubule-associated protein that also interacts with retromer. Aging attenuates the dynein-dynactin interaction, and dynein dysfunction reproduces age-dependent endocytic disturbance, resulting in the intracellular accumulation of beta-amyloid precursor protein (APP) and its β-cleavage products, including Aβ. Here, we report that aging itself affects retromer trafficking in cynomolgus monkey brains. In addition, dynein dysfunction reproduces this type of age-dependent retromer deficiency (ie, the endosomal accumulation of retromer-related proteins and APP. Moreover, we found that knockdown of Rab7, Rab9, or Rab11 did not alter endogenous APP metabolism, such as that observed in aged monkey brains and in dynein-depleted cells. These findings suggest that dynein dysfunction can cause retromer deficiency and that concomitant disruption of retrograde trafficking may be the key factor underlying age-dependent Aβ pathology. PMID:27179390

  2. Identification of Protein Carbonyls in serum of the fetal and neonatal pig.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidation of serum proteins leads to non-reversible carbonyl formation which alters their function and has long been associated with stress-related disease processes. The primary objective of this study was to identify oxidized serum protein biomarkers of metabolic stress in baby pigs. Protein carb...

  3. 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

  4. Oxi-DIGE: A novel proteomic approach for detecting and quantifying carbonylated proteins.

    PubMed

    Baraibar, Martin; Ladouce, Romain; Friguet, Bertrand

    2014-10-01

    Proteins are involved in key cellular functions and our health and wellness depends on their quality. Accumulation of oxidatively damaged proteins is a hallmark of deleterious processes such increased oxidative stress, chronic inflammation, ageing and age-related diseases. Thus, quantifying and identifying oxidized proteins is a biomarker of choice for monitoring biological ageing and/or the efficiency of anti-oxidant, ant-inflammatory and anti-ageing therapies. However, the absence of reliable tools for analyses has inhibited its establishment as the gold standard for measuring the efficacy of anti-ageing and age related diseases interventions. Herein, we present a novel proteomics technology, named Oxi-DIGE?, which provides a significant improvement in terms of specificity, reproducibility and statistical support for proteomic analysis of carbonylated proteins. In Oxi-DIGE, protein carbonyls are labelled with fluorescent hydrazide probes that bind specifically to carbonyl groups in proteins. Experimental groups (e.g. control and experimental samples) are labelled with different flurophore-binded hydrazides that fluoresce light at different wavelengths, producing different colour fluorescence. Thus samples from different experimental groups are co-resolved on a single 2D gel. Increased accuracy is provided due to: (i) reduced false positives by using an exogenous synthetic fluorescent tag; (ii) multiplexing, that is the possibility to run multiple samples on the same gel, (iii) the use of an internal standard on each gel which eliminates inter-gel variations and provides an increased statistical confidence. In addition, the resolution of the carbonyl groups is improved, forming distinct spots that can be identified by mass spectrometry. ?Patent Application (M. Baraibar, R. Ladouce., B. Friguet, A method for detecting and/or quantifying carbonylated proteins (WO/2012/175519) filed by UPMC and referring to the technology described in this abstract. PMID:26461312

  5. Iron Dextran treatment does not induce serum protein carbonyls in the newborn pig

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidation of serum proteins can lead to carbonyl formation which alters their function and is often associated with stress-related diseases. Since it is recommended that all pigs reared in modern production facilities be given supplemental iron at birth to prevent anemia, and metals can catalyze th...

  6. A structural role for arginine in proteins: multiple hydrogen bonds to backbone carbonyl oxygens.

    PubMed

    Borders, C L; Broadwater, J A; Bekeny, P A; Salmon, J E; Lee, A S; Eldridge, A M; Pett, V B

    1994-04-01

    We propose that arginine side chains often play a previously unappreciated general structural role in the maintenance of tertiary structure in proteins, wherein the positively charged guanidinium group forms multiple hydrogen bonds to backbone carbonyl oxygens. Using as a criterion for a "structural" arginine one that forms 4 or more hydrogen bonds to 3 or more backbone carbonyl oxygens, we have used molecular graphics to locate arginines of interest in 4 proteins: Arg 180 in Thermus thermophilus manganese superoxide dismutase, Arg 254 in human carbonic anhydrase II, Arg 31 in Streptomyces rubiginosus xylose isomerase, and Arg 313 in Rhodospirillum rubrum ribulose-1,5-bisphosphate carboxylase/oxygenase. Arg 180 helps to mold the active site channel of superoxide dismutase, whereas in each of the other enzymes the structural arginine is buried in the "mantle" (i.e., inside, but near the surface) of the protein interior well removed from the active site, where it makes 5 hydrogen bonds to 4 backbone carbonyl oxygens. Using a more relaxed criterion of 3 or more hydrogen bonds to 2 or more backbone carbonyl oxygens, arginines that play a potentially important structural role were found in yeast enolase, Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase, bacteriophage T4 and human lysozymes, Enteromorpha prolifera plastocyanin, HIV-1 protease, Trypanosoma brucei brucei and yeast triosephosphate isomerases, and Escherichia coli trp aporepressor (but not trp repressor or the trp repressor/operator complex).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8003972

  7. 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

  8. 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

  9. 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).

  10. 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

  11. 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

  12. 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

  13. 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

  14. Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

    SciTech Connect

    Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

    1988-07-12

    The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.

  15. 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. PMID:25089792

  16. Increased nitration and carbonylation of proteins in MRL +/+ mice exposed to trichloroethene: Potential role of protein oxidation in autoimmunity

    SciTech Connect

    Wang Gangduo; Wang Jianling; Ma Huaxian; Khan, M. Firoze

    2009-06-01

    Even though reactive oxygen and nitrogen species (RONS) are implicated as mediators of autoimmune diseases (ADs), little is known about contribution of protein oxidation (carbonylation and nitration) in the pathogenesis of such diseases. The focus of this study was, therefore, to establish a link between protein oxidation and induction and/or exacerbation of autoimmunity. To achieve this, female MRL +/+ mice were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 6 or 12 weeks (10 mmol/kg, i.p., every 4{sup th} day). TCE treatment resulted in significantly increased formation of nitrotyrosine (NT) and induction of iNOS in the serum at both 6 and 12 weeks of treatment, but the response was greater at 12 weeks. Likewise, TCE treatment led to greater NT formation, and iNOS protein and mRNA expression in the livers and kidneys. Moreover, TCE treatment also caused significant increases ({approx}3 fold) in serum protein carbonyls (a marker of protein oxidation) at both 6 and 12 weeks. Significantly increased protein carbonyls were also observed in the livers and kidneys (2.1 and 1.3 fold, respectively) at 6 weeks, and to a greater extent at 12 weeks (3.5 and 2.1 fold, respectively) following TCE treatment. The increases in TCE-induced protein oxidation (carbonylation and nitration) were associated with significant increases in Th1 specific cytokine (IL-2, IFN-{gamma}) release into splenocyte cultures. These results suggest an association between protein oxidation and induction/exacerbation of autoimmune response. The results present a potential mechanism by which oxidatively modified proteins could contribute to TCE-induced autoimmune response and necessitates further investigations for clearly establishing the role of protein oxidation in the pathogenesis of ADs.

  17. 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

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

    PubMed

    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

  19. Inhibition of protein carbonyl formation and lipid peroxidation by glutathione in rat liver microsomes.

    PubMed

    Palamanda, J R; Kehrer, J P

    1992-02-14

    The peroxidation of rat liver microsomal lipids is stimulated in the presence of iron by the addition of NADPH or ascorbate and is inhibited by the addition of glutathione (GSH). The fate of GSH and the oxidative modification of proteins under these conditions have not been well studied. Rat liver microsomes were incubated at 37 degrees C under 95% O2:5% CO2 in the presence of 10 microM ferric chloride, 400 microM ADP, and either 450 microM ascorbic acid or 400 microM NADPH. Lipid peroxidation was assessed in the presence 0, 0.2, 0.5, 1, or 5 mM GSH by measuring thiobarbituric acid reactive substance (TBARS) and oxidative modification of proteins by measuring protein thiol and carbonyl groups. GSH inhibited TBARS and protein carbonyl group formation in both ascorbate and NADPH systems in a dose-dependent manner. Heat denaturing of microsomes or treatment with trypsin resulted in the loss of this protection. The formation of protein carbonyl groups could be duplicated by incubating microsomes with 4-hydroxynonenal. Ascorbate-dependent peroxidation caused a loss of protein thiol groups which was diminished by GSH only in fresh microsomes. Both boiling and trypsin treatment significantly decreased the basal protein thiol content of microsomes and enhanced ascorbate-stimulated lipid peroxidation. Protection against protein carbonyl group formation by GSH correlated with the inhibition of lipid peroxidation and appeared not to be due to the formation of the GSH conjugate of 4-hydroxynonenal as only trace amounts of this conjugate were detected. Ninety percent of the GSH lost after 60 min of peroxidation was recoverable as borohydride reducible material in the supernatant fraction. The remaining 10% could be accounted for as GSH-bound protein mixed disulfides. However, only 75% of the GSH lost during peroxidation appeared as glutathione disulfide, suggesting that some was converted to other soluble borohydride reducible forms. These data support a role for protein thiol

  20. 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

  1. Gel-free proteomic methodologies to study reversible cysteine oxidation and irreversible protein carbonyl formation.

    PubMed

    Boronat, S; García-Santamarina, S; Hidalgo, E

    2015-05-01

    Oxidative modifications in proteins have been traditionally considered as hallmarks of damage by oxidative stress and aging. However, oxidants can generate a huge variety of reversible and irreversible modifications in amino acid side chains as well as in the protein backbones, and these post-translational modifications can contribute to the activation of signal transduction pathways, and also mediate the toxicity of oxidants. Among the reversible modifications, the most relevant ones are those arising from cysteine oxidation. Thus, formation of sulfenic acid or disulfide bonds is known to occur in many enzymes as part of their catalytic cycles, and it also participates in the activation of signaling cascades. Furthermore, these reversible modifications have been usually attributed with a protective role, since they may prevent the formation of irreversible damage by scavenging reactive oxygen species. Among irreversible modifications, protein carbonyl formation has been linked to damage and death, since it cannot be repaired and can lead to protein loss-of-function and to the formation of protein aggregates. This review is aimed at researchers interested on the biological consequences of oxidative stress, both at the level of signaling and toxicity. Here we are providing a concise overview on current mass-spectrometry-based methodologies to detect reversible cysteine oxidation and irreversible protein carbonyl formation in proteomes. We do not pretend to impose any of the different methodologies, but rather to provide an objective catwalk on published gel-free approaches to detect those two types of modifications, from a biologist's point of view. PMID:25782062

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

    PubMed

    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

  3. 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

  4. Affinity chromatographic selection of carbonylated proteins followed by identification of oxidation sites using tandem mass spectrometry.

    PubMed

    Mirzaei, Hamid; Regnier, Fred

    2005-04-15

    It has been shown that oxidatively modified forms of proteins accumulate during oxidative stress, aging, and in some age-related diseases. One of the unique features of a wide variety of routes by which proteins are oxidized is the generation of carbonyl groups. This paper reports a method for the isolation of oxidized proteins, which involves (1) biotinylation of oxidized proteins with biotin hydrazide and (2) affinity enrichment using monomeric avidin affinity chromatography columns. The selectivity of the method was validated by adding in vitro oxidized biotinylated BSA to a yeast lysate and showing that the predominant protein recovered was BSA. This method was applied to the question of whether large doses of 2-nitropropane produce oxidized proteins. A study of rat liver homogenates showed that animals dosed with 2-nitropropane produced 17 times more oxidized protein than controls in 6 h. Tryptic digestion of these oxidized proteins followed by reversed-phase chromatography and tandem mass spectrometry led to the identification of 14 peptides and their parent proteins. Nine of the 14 identified peptides were found to carry 1 or 2 oxidation sites and 5 of the 9 peptides were biotinylated. The significance of this affinity method is that it allows the isolation of oxidized proteins from the rest of the proteome and facilitates their identification. In some cases, it is even possible to identify the site of oxidation. PMID:15828771

  5. Protein carbonyls and traditional biomarkers in pigs exposed to low-dose γ-radiation.

    PubMed

    Smutná, Miriam; Beňová, Katarína; Dvořák, Petr; Nekvapil, Tomáš; Kopřiva, Vladimír; Maté, Dionýz

    2013-04-01

    Response of pigs to irradiation manifested by production of protein carbonyls and adaptable enzymes was studied in two experiments. In one experiment, 10 mixed-sex pigs were exposed to 0.5 Gy whole body (60)Co irradiation. In the other experiment, another batch of 10 pigs was exposed to 1.0 Gy half-body irradiation. Unlike those exposed to half-body irradiation, the pigs exposed to whole-body irradiation showed significant increase in protein carbonyls by 73%, and a decrease in cholesterol by 25.7%, compared to the control group. In both cases of dose-dependent irradiation exposure, pigs showed a decrease in alanine aminotransferase activity compared with the control group. At the dose of 1 Gy, ALT activity decreased significantly by 27.7%. Aspartate aminotransferase activity in pigs after half-body irradiation decreased significantly by 65.5%. Although low doses of ionizing radiation were applied, monitoring of the above biochemical parameters helped define the pigs' biological response. PMID:23021124

  6. Histone retention, protein carbonylation, and lipid peroxidation in spermatozoa: Possible role in recurrent pregnancy loss.

    PubMed

    Mohanty, Gayatri; Swain, Nirlipta; Goswami, Chandan; Kar, Sujata; Samanta, Luna

    2016-06-01

    Contribution from a defective paternal genome has been attributed to be an important cause for spontaneous recurrent pregnancy loss (RPL). Increased oxidative stress results in decreased detoxification and is a cause for damage to chromatin, proteins, and membrane lipids. The present study aimed to explore if there is a significant relationship between retained histones due to defective packaging of DNA in spermatozoa and oxidative stress. RPL patients (n=16) with a history of ≥2 embryo losses before the 20th week of gestation and no female factor abnormality, and fertile healthy volunteers (n=20) as controls were included in the study. A significant difference in the levels of protein carbonylation and lipid peroxidation together with an increased retention of histones in the experimental groups was noticed. Histone carrying sites for oxidative modification such as arginine and lysine might be responsible for disturbing the paternal epigenomic control during early stages of embryonic differentiation leading to abortion. PMID:26980262

  7. 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

  8. 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. PMID:25332112

  9. 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. PMID:18444136

  10. 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

  11. Effects of Ramadan Fasting on Serum Amyloid A and Protein Carbonyl Group Levels in Patients With Cardiovascular Diseases

    PubMed Central

    Asadi, Hami; Abolfathi, Ali Akbar; Badalzadeh, Reza; Majidinia, Maryam; Yaghoubi, Alireza; Asadi, Maryam; Yousefi, Bahman

    2015-01-01

    Introduction: Serum amyloid-A (SAA) and protein carbonyl group are rigorously related with cardiovascular diseases (CVDs) as a sensitive marker of an acute inflammatory state and as an important index of oxidative stress, respectively. Moreover, diet is one of the main factors that can modify cardiovascular risks. Therefore, this study aimed to investigate the effects of Ramadan fasting on SAA and protein carbonyl group levels in patients with CVDs. Methods: Twenty-one patients (21 male; mean age 52±9 years old) with CVDs (coronary artery disease, cerebrovascular, or peripheral arterial diseases) were participated in this study. Biochemical parameters were measured in patients 2 days before and 2 days after Ramadan fasting. SAA levels were assessed using enzyme-linked immunosorbent assay and Cayman’s protein carbonyl colorimetric assay was provided for measuring protein carbonyl groups. Results: According to the findings of the study, post-Ramadan levels of inflammatory biomarker, SAA was decreased significantly in patients with CVDs in comparison with the baseline before-fasting values (16.84±8.20 vs. 24.40±6.72 μg/ml, P = 0.021). In addition, Ramadan fasting significantly reduced the levels of protein carbonyl group in patients as compared with those of baseline values (33.08±15.31 vs. 43.65±16.88 nmol/ml, P = 0.039). Conclusion: Ramadan fasting has impressive effects on modulating CVDs by decreasing inflammation and oxidative stress markers. However, to get a clear conclusion with more results, further investigation is warranted. PMID:26191392

  12. 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

  13. Analysis of protein oxidation in serum of fetal and newborn piglets and the influence of iron dextran on induction of protein carbonyls.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods were employed to evaluate serum biomarkers associated with protein oxidative stress and damage, to determine potential sources of metabolic stress in baby pigs. Protein carbonyls in serum were converted to dinitrophenyl (DNP) derivatives with DNP-hydrazine, precipitated with TCA, extracted i...

  14. Protein carbonyls and antioxidant defenses in corkwing wrasse (Symphodus melops) from a heavy metal polluted and a PAH polluted site.

    PubMed

    Almroth, Bethanie Carney; Sturve, Joachim; Stephensen, Eiríkur; Holth, Tor Fredrik; Förlin, Lars

    2008-08-01

    The use of fish in environmental monitoring has become increasingly important in recent years as anthropogenic substances, many of which function as prooxidants, are accumulating in aquatic environments. We have measured a battery of antioxidant defenses as a measure of oxidative status, as well as protein carbonylation as a measure of oxidative damage, in corkwing wrasse (Symphodus melops) captured near a disused copper mine, where water and sediment are contaminated with heavy metals, and an aluminum smelter, a site contaminated with PAHs. Results were compared to two different reference sites. Fish at the heavy metal site had lower glucose-6-phosphate dehydrogenase activity and elevated protein carbonyls (1.8 times) compared to fish from the reference site. At the PAH site, EROD was increased 2-fold, while total glutathione and methemoglobin reductase concentration, were decreased. No differences were seen in protein carbonyl levels at the PAH site. Measures of both antioxidant defenses and oxidative damage should be used when assessing effects of xenobiotics on oxidative stress in fish species. PMID:18490050

  15. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25205819

  17. Cellular location and age-dependent changes of the regulatory subunits of cAMP-dependent protein kinase in rat testis.

    PubMed

    Landmark, B F; Oyen, O; Skålhegg, B S; Fauske, B; Jahnsen, T; Hansson, V

    1993-11-01

    This study was undertaken to examine the expression and cellular location of the various cAMP-dependent protein kinase (PKA) subunits in different testicular cell types, using cDNA probes, isoenzyme-specific antibodies and activity measurements. Amounts of mRNA and protein were examined in cultured Sertoli cells, cultured peritubular cells, germ cells (pachytene spermatocytes, round spermatids), Leydig cell tumours as well as whole testes from rats of various ages. In Sertoli cells, there was a good correlation between the amount of mRNA and the respective immunoreactive proteins. In other types of cell, such as germ cells and Leydig tumour cells, this was not always the case. Large amounts of RII beta mRNA were found in Leydig tumour cells, whereas the amount of immunoreactive protein was low. Furthermore, large amounts of small-sized, germ cell-specific mRNAs for RI alpha (1.7 kb) and RII alpha (2.2 kb) were also found in the developing rat testis after 30 to 40 days of age, but the large amounts of mRNA were only partially reflected at the protein level. Pachytene spermatocytes and round spermatids were practically devoid of both RII alpha and RII beta protein. During spermatid differentiation, there was a decrease in RI alpha and an increase in RII alpha protein. Cell specific distribution of the various PKA subunits in testicular cell types is described. In some types of cell, discrepancies between mRNA and protein were demonstrated, which clearly suggest cell specific differences in translational efficiencies for some of these mRNAs, particularly the small-sized mRNAs for RI alpha and RII alpha in meiotic and post-meiotic germ cells. PMID:8107013

  18. Hippocampal Extracellular Matrix Levels and Stochasticity in Synaptic Protein Expression Increase with Age and Are Associated with Age-dependent Cognitive Decline*

    PubMed Central

    Végh, Marlene J.; Rausell, Antonio; Loos, Maarten; Heldring, Céline M.; Jurkowski, Wiktor; van Nierop, Pim; Paliukhovich, Iryna; Li, Ka Wan; del Sol, Antonio; Smit, August B.; Spijker, Sabine; van Kesteren, Ronald E.

    2014-01-01

    Age-related cognitive decline is a serious health concern in our aging society. Decreased cognitive function observed during healthy brain aging is most likely caused by changes in brain connectivity and synaptic dysfunction in particular brain regions. Here we show that aged C57BL/6J wild-type mice have hippocampus-dependent spatial memory impairments. To identify the molecular mechanisms that are relevant to these memory deficits, we investigated the temporal profile of mouse hippocampal synaptic proteome changes at 20, 40, 50, 60, 70, 80, 90, and 100 weeks of age. Extracellular matrix proteins were the only group of proteins that showed robust and progressive up-regulation over time. This was confirmed by immunoblotting and histochemical analysis, which indicated that the increased levels of hippocampal extracellular matrix might limit synaptic plasticity as a potential cause of age-related cognitive decline. In addition, we observed that stochasticity in synaptic protein expression increased with age, in particular for proteins that were previously linked with various neurodegenerative diseases, whereas low variance in expression was observed for proteins that play a basal role in neuronal function and synaptic neurotransmission. Together, our findings show that both specific changes and increased variance in synaptic protein expression are associated with aging and may underlie reduced synaptic plasticity and impaired cognitive performance in old age. PMID:25044018

  19. Age-dependent changes in the protein expression levels of Redd1 and mTOR in the gerbil hippocampus during normal aging

    PubMed Central

    CHOI, HEE-SOO; AHN, JI HYEON; PARK, JOON HA; WON, MOO-HO; LEE, CHOONG-HYUN

    2016-01-01

    Redd1, also known as RTP801/Dig2/DDIT4, is a stress-induced protein and a negative regulator of mammalian target of rapamycin (mTOR). Redd1 is also closely associated with oxidative stress and DNA damage. In the present study, age-related changes in the protein expression levels of mTOR and Redd1 were investigated using immunohistochemistry and western blot in the gerbil hippocampus at postnatal month (PM) 3, 6, 12 and 24. No significant differences were identified in the levels of mTOR among the experimental groups, whereas, the levels of phosphorylated mTOR decreased with age. The protein expression levels of Redd1 were observed to gradually increase with age; in the PM 24 group, the level was significantly increased (~189.2%), compared with the PM 3 group. In addition, Redd1 immunoreactivity was significantly increased in the hippocampal principal neurons of the PM 24 group, including the pyramidal cells in the hippocampus proper and granule cells in the dentate gyrus, compared with the other experimental groups. These results demonstrated that the protein expression of Redd1 in the hippocampus was markedly increased during normal aging, indicating that the age-related increase in the expression of Redd1 may be closely associated with age-related hippocampal change. PMID:26846432

  20. Age-dependent changes in the protein expression levels of Redd1 and mTOR in the gerbil hippocampus during normal aging.

    PubMed

    Choi, Hee-Soo; Ahn, Ji Hyeon; Park, Joon Ha; Won, Moo-Ho; Lee, Choong-Hyun

    2016-03-01

    Redd1, also known as RTP801/Dig2/DDIT4, is a stress-induced protein and a negative regulator of mammalian target of rapamycin (mTOR). Redd1 is also closely associated with oxidative stress and DNA damage. In the present study, age‑related changes in the protein expression levels of mTOR and Redd1 were investigated using immunohistochemistry and western blot in the gerbil hippocampus at postnatal month (PM) 3, 6, 12 and 24. No significant differences were identified in the levels of mTOR among the experimental groups, whereas, the levels of phosphorylated mTOR decreased with age. The protein expression levels of Redd1 were observed to gradually increase with age; in the PM 24 group, the level was significantly increased (~189.2%), compared with the PM 3 group. In addition, Redd1 immunoreactivity was significantly increased in the hippocampal principal neurons of the PM 24 group, including the pyramidal cells in the hippocampus proper and granule cells in the dentate gyrus, compared with the other experimental groups. These results demonstrated that the protein expression of Redd1 in the hippocampus was markedly increased during normal aging, indicating that the age-related increase in the expression of Redd1 may be closely associated with age-related hippocampal change. PMID:26846432

  1. Carbonyl carbon transverse relaxation dispersion measurements and ms-micros timescale motion in a protein hydrogen bond network.

    PubMed

    Ishima, Rieko; Baber, James; Louis, John M; Torchia, Dennis A

    2004-06-01

    A constant-time, Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation, R(2), dispersion experiment for carbonyl carbons was designed and executed to detect micros-ms time-scale dynamics of protein backbone carbonyl sites. Because of the large (ca. 55 Hz) C(alpha)-C' J-coupling, the carbonyl signal intensity is strongly modulated as the spacing between CPMG pulses is varied, in uniformly (13)C enriched proteins, unless care is taken to minimize the perturbation of the C(alpha) magnetization by the CPMG pulses. CPMG pulse trains consisting of either a band-selective pulse, such as RE-BURP, or rectangular (with an excitation null in the C(alpha) region of the spectrum) pulses were employed in order to minimize C' signal modulation by C(alpha)-C' J-coupling. The performance of these types of CPMG refocusing pulses was assessed by computer simulation, and by comparing dispersion profiles measured for (1) uniformly [(13)C,(15)N, (2)H] ((2)H at non-labile hydrogen sites) labeled, and (2) uniformly (15)N/selectively-(13)C' labeled samples of HIV-1 protease bound to a potent inhibitor, DMP323. In addition, because the uniformly (13)C/(15)N/(2)H labeled sample was well suited to measure (15)N and (1)H R(2) dispersion as well as (13)C' dispersion, conformational exchange in the inter subunit beta-sheet hydrogen-bond network of the inhibitor-bound protease was elucidated using relaxation dispersion data of all three types of nuclei. PMID:15014232

  2. 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

  3. Age-dependent changes in nitric oxide synthase activity and protein expression in striata of mice transgenic for the Huntington's disease mutation.

    PubMed

    Pérez-Severiano, Francisca; Escalante, Bruno; Vergara, Paula; Ríos, Camilo; Segovia, José

    2002-09-27

    Huntington's disease (HD) is an autosomal hereditary neurodegenerative disorder caused by an abnormal expansion of the CAG repeats that code for a polyglutamine tract in a novel protein called huntingtin (htt). Both patients and experimental animals exhibit oxidative damage in specific areas of the brain, particularly the striatum. Nitric oxide (NO) is involved in many different physiological processes, and under pathological conditions it may promote oxidative damage through the formation of the highly reactive metabolite peroxynitrite; however, it may also play a role protecting cells from oxidative damage. We previously showed a correlation between the progression of the neurological phenotype and striatal oxidative damage in a line of transgenic mice, R6/1, which expresses a human mutated htt exon 1 with 116 CAG repeats. The purpose of the present work was to explore the participation of NO in the progressive oxidative damage that occurs in the striata of R6/1 mice. We analyzed the role of NO by measuring the activity of nitric oxide synthase (NOS) in the striata of transgenic and control mice at different ages. There was no difference in NOS activity between transgenic and wild-type mice at 11 weeks of age. In contrast, 19-week-old transgenic mice showed a significant increase in NOS activity, compared with same age controls. By 35 weeks of age, there was a decrease in NOS activity in transgenic mice when compared with wild-type controls. NOS protein expression was also determined in 11-, 19- and 35-week-old transgenic mice and wild-type littermates. Our results show increased neuronal NOS expression in 19-week-old transgenic mice, followed by a decreased level in 35-week-old mice, compared with controls, a phenomenon that parallels the changes in NOS enzyme activity. The present results suggest that NO is involved in the process leading to striatal oxidative damage and that it is associated with the onset of the progressive neurological phenotype in mice

  4. 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

  5. Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction

    PubMed Central

    Vågberg, Mattias; Norgren, Niklas; Dring, Ann; Lindqvist, Thomas; Birgander, Richard; Zetterberg, Henrik; Svenningsson, Anders

    2015-01-01

    Background Neurofilament light (NFL) and Glial Fibrillary Acidic Protein (GFAP) are integral parts of the axonal and astrocytal cytoskeletons respectively and are released into the cerebrospinal fluid (CSF) in cases of cellular damage. In order to interpret the levels of these biomarkers in disease states, knowledge on normal levels in the healthy is required. Another biomarker for neurodegeneration is brain atrophy, commonly measured as brain parenchymal fraction (BPF) using magnetic resonance imaging (MRI). Potential correlations between levels of NFL, GFAP and BPF in healthy individuals have not been investigated. Objectives To present levels of NFL and GFAP in healthy individuals stratified for age, and investigate the correlation between them as well as their correlation with BPF. Methods The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample missing for GFAP analysis) and 48 of the volunteers underwent determination of BPF using MRI. Results Mean (±SD) NFL was 355 ng/L (±214), mean GFAP was 421 ng/L (±129) and mean BPF was 0.867 (±0.035). All three biomarkers correlated with age. NFL also correlated with both GFAP and BPF. When controlled for age, only the correlation between NFL and GFAP retained statistical significance. Conclusions This study presents data on age-stratified levels of NFL and GFAP in the CSF of healthy individuals. There is a correlation between levels of NFL and GFAP and both increase with age. A correlation between NFL and BPF was also found, but did not retain statistical significance if controlled for age. PMID:26317831

  6. Apple phenolics as inhibitors of the carbonylation pathway during in vitro metal-catalyzed oxidation of myofibrillar proteins.

    PubMed

    Rysman, Tine; Utrera, Mariana; Morcuende, David; Van Royen, Geert; Van Weyenberg, Stephanie; De Smet, Stefaan; Estévez, Mario

    2016-11-15

    The effect of apple phenolics on the oxidative damage caused to myofibrillar proteins by an in vitro metal-catalyzed oxidation system was investigated. Three pure phenolic compounds (chlorogenic acid, (-)-epicatechin and phloridzin) and an apple peel extract were added to myofibrillar proteins in three concentrations (50, 100 and 200μM), and a blank treatment was included as a control. All suspensions were subjected to Fe(3+)/H2O2 oxidation at 37°C during 10days, and protein oxidation was evaluated as carbonylation (α-amino adipic and γ-glutamic semialdehydes) and Schiff base cross-links. Significant inhibition by apple phenolics was found as compared to the control treatment, with (-)-epicatechin being the most efficient antioxidant and phloridzin showing the weakest antioxidant effect. The higher concentrations of apple extract showed effective antioxidant activity against protein oxidation in myofibrillar proteins, emphasizing the potential of apple by-products as natural inhibitors of protein oxidation in meat products. PMID:27283697

  7. 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

  8. 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

  9. 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

  10. Age-dependence of free radical-induced oxidative damage in ischemic-reperfused rat heart.

    PubMed

    Nagy, K; Takács, I E; Pankucsi, C

    1996-01-01

    Oxygen free radical-induced oxidative damage is involved in both aging and ischemia-reperfusion. The purpose of this study was to determine the aging-induced oxidative alterations in rat heart as well as the age-dependence of heart injury following ischemia-reperfusion. A comparative study was performed on young and old ischemic-reperfused rat hearts. Protein oxidation and the ascorbyl radical level in heart tissue were determined in order to characterize the oxidative stress. Comparing the control conditions, old hearts have 31% more oxidized proteins as measured by protein carbonyl content, and 18% lower ascorbyl radical level as determined by ESR, than young ones. The extent of increase of protein oxidation and ascorbyl free radical depletion induced by ischemia-reperfusion is less pronounced in the old hearts (7 and 8% respectively), as compared to the young ones (55 and 21% respectively). Pre-treatment with a free radical scavenger, such as centrophenoxine, diminished the ischemia-reperfusion injury in both young and old rat hearts. PMID:15374178

  11. 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

  12. 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.

  13. 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

  14. 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. PMID:25787825

  15. 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

  16. 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

  17. 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

  18. Oxime conjugation in protein chemistry: from carbonyl incorporation to nucleophilic catalysis.

    PubMed

    Agten, Stijn M; Dawson, Philip E; Hackeng, Tilman M

    2016-05-01

    Use of oxime forming reactions has become a widely applied strategy for peptide and protein bioconjugation. The efficiency of the reaction and robust stability of the oxime product has led to the development of a growing list of methods to introduce the required ketone or aldehyde functionality site specifically into proteins. Early methods focused on site-specific oxidation of an N-terminal serine or threonine and more recently transamination methods have been developed to convert a broader set of N-terminal amino acids into a ketone or aldehyde. More recently, site-specific modification of protein has been attained through engineering enzymes involved in posttranslational modifications in order to accommodate aldehyde-containing substrates. Similarly, a growing list of unnatural amino acids can be introduced through development of selective amino-acyl tRNA synthetase/tRNA pairs combined with codon reassignment. In the case of glycoproteins, glycans can be selectively modified chemically or enzymatically to introduce aldehyde functional groups. Finally, the total chemical synthesis of proteins complements these biological and chemoenzymatic approaches. Once introduced, the oxime ligation of these aldehyde and ketone groups can be catalyzed by aniline or a variety of aniline derivatives to tune the activity, pH preference, stability and solubility of the catalyst. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27006095

  19. Conformationally Constrained Analogues of Diacylglycerol (DAG). 25. Exploration of the sn-1 and sn-2 carbonyl functionality reveals the essential role of the sn-1 carbonyl at the lipid interface in the binding of DAG-lactones to protein kinase C

    PubMed Central

    Kang, Ji-Hye; Peach, Megan L.; Pu, Yongmei; Lewin, Nancy E.; Nicklaus, Marc C.; Blumberg, Peter M.; Marquez, Victor E.

    2008-01-01

    A group of DAG-lactones with altered functionality (C=O → CH2 or C=O → C=S) at the sn-1 and sn-2 carbonyl pharmacophores was synthesized and used as probes to dissect the individual role of each carbonyl in binding to protein kinase C (PKC). The results suggest that the hydrated sn-1 carbonyl is engaged in very strong hydrogen bonding interactions with the charged lipid headgroups and organized water molecules at the lipid interface. Conversely, the sn-2 carbonyl has a more modest contribution to the binding process as a result of its involvement with the receptor (C1 domain) via conventional hydrogen bonding to the protein. The parent DAG-lactones, E-6 and Z-7, were designed to bind exclusively in the sn-2 binding mode to insure the correct orientation and disposition of pharmacophores at the binding site. PMID:16134942

  20. 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

  1. Ischemia-reperfusion rat model of acute pancreatitis: protein carbonyl as a putative early biomarker of pancreatic injury.

    PubMed

    Schanaider, Alberto; de Carvalho, Thales Penna; de Oliveira Coelho, Simone; Renteria, Juan Miguel; Eleuthério, Elis Cristina Araújo; Castelo-Branco, Morgana Teixeira Lima; Madi, Kalil; Baetas-da-Cruz, Wagner; de Souza, Heitor Siffert Pereira

    2015-08-01

    Acute pancreatitis (AP) is an inflammatory disorder that can affect adjacent and/or remote organs. Some evidence indicates that the production of reactive oxygen species is able to induce AP. Protein carbonyl (PC) derivatives, which can also be generated through oxidative cleavage mechanisms, have been implicated in several diseases, but there is little or no information on this biomarker in AP. We investigated the association between some inflammatory mediators and PC, with the severity of ischemia-reperfusion AP. Wistar rats (n = 56) were randomly assigned in the following groups : control; sham, 15- or 180-min clamping of splenic artery, with 24 or 72 h of follow-up. The relationships between serum level of PC and thiobarbituric acid reactive species (TBARS) to myeloperoxidase (MPO) activity in tissue homogenates and to cytokines in culture supernatants of pancreatic samples were analyzed. MPO activity was related to the histology scores and increased in all clamping groups. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 were higher in the 180-min groups. Significant correlations were found between MPO activity and the concentrations of TNF-α and IL-1β. PC levels increased in the 15-min to 24-h group. TBARS levels were not altered substantially. MPO activity and TNF-α and IL-1β concentrations in pancreatic tissue are correlated with AP severity. Serum levels of PC appear to begin to rise early in the course of the ischemia-reperfusion AP and are no longer detected at later stages in the absence of severe pancreatitis. These data suggest that PC can be an efficient tool for the diagnosis of early stages of AP. PMID:24934325

  2. The pro-oxidant buthionine sulfoximine (BSO) reduces tumor growth of implanted Lewis lung carcinoma in mice associated with increased protein carbonyl, tubulin abundance, and aminopeptidase activity.

    PubMed

    Rodríguez-Gómez, Isabel; Carmona-Cortés, Javier; Wangensteen, Rosemary; Vargas-Tendero, Pablo; Banegas, Inmaculada; Quesada, Andrés; García-Lora, Angel M; Vargas, Félix

    2014-08-01

    This study evaluated the effects of the pro-oxidant buthionine sulfoximine (BSO) and of the interaction between BSO and TETRAC, an antagonist of αvß3 integrin, on tumor development and aminopeptidase (AP) activity in a murine model of implanted Lewis's carcinoma. Male CBA-C57 mice were untreated (controls) or treated with BSO (222 mg/100 mL in drinking water), TETRAC (10 mg/kg/day, i.p.), or BSO + TETRAC. BSO for 28 days and TETRAC were given for the last 20 days. Mice were subcutaneously inoculated with 1 × 10(6) Lewis carcinoma 3LL cells into the dorsum. Study variables were tumor weight (TW); Hb, as index of tumor-mediated angiogenesis; vascular endothelial growth factor (VEGF) protein abundance; protein carbonyl content; α-tubulin abundance; and GluAp, AlaAp, and AspAp activities. BSO produced a major decrease in TW (203 ± 18 mg) with respect to controls (365 ± 26) and a reduction in Hb content. The TETRAC group also showed marked reductions in TW (129 ± 15) and Hb concentration associated with a reduced VEGF content. The BSO + TETRAC group showed a major TW reduction (125 ± 13); although, the difference with the TETRAC group was not significant. BSO treatment increased protein carbonyl and tubulin abundance in comparison to controls. The activity of all APs was increased in the three experimental groups and was strongly and negatively correlated with TW. In conclusion, administration of BSO reduced the TW, which inversely correlated with protein carbonyl content, suggesting a loss of microtubule polymerization. The finding of a negative correlation between TW and AP activity opens up new perspectives for the study of APs as tumor growth modulators. PMID:24816945

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Mitochondrial uncoupler carbonyl cyanide M-chlorophenylhydrazone induces the multimer assembly and activity of repair enzyme protein L-isoaspartyl methyltransferase.

    PubMed

    Fanélus, Irvens; Desrosiers, Richard R

    2013-07-01

    The protein L-isoaspartyl methyltransferase (PIMT) repairs damaged aspartyl residues in proteins. It is commonly described as a cytosolic protein highly expressed in brain tissues. Here, we report that PIMT is an active monomeric as well as a multimeric protein in mitochondria isolated from neuroblastoma cells. Upon treatments with mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), PIMT monomers level decreased by half while that of PIMT multimers was higher. Gel electrophoresis under reducing conditions of CCCP-induced PIMT multimers led to PIMT monomers accumulation, indicating that multimers resulted from disulfide-linked PIMT monomers. The antioxidant ascorbic acid significantly lowered CCCP-induced formation of PIMT multimers, suggesting that reactive oxygen species contributed to PIMT multimerization. In addition, the elevation of PIMT multimers catalytic activity upon treatments with CCCP was severely inhibited by the reducing agent dithiothreitol. This indicated that PIMT monomers have lower enzymatic activity following CCCP treatments and that activation of PIMT multimers is essentially dependent on the formation of disulfide-linked monomers of PIMT. Furthermore, the perturbation of mitochondrial function by CCCP promoted the accumulation of damaged aspartyl residues in proteins with high molecular weights. Thus, this study demonstrates the formation of active PIMT multimers associated with mitochondria that could play a key role in repairing damaged proteins accumulating during mitochondrial dysfunction. PMID:23319267

  9. Human serum metabolic profiles are age dependent.

    PubMed

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-12-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32-81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10(-04) to 7.8 × 10(-42) , α(corr) = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  10. Oxidative stress induced carbonylation in human plasma.

    PubMed

    Madian, Ashraf G; Diaz-Maldonado, Naomi; Gao, Qiang; Regnier, Fred E

    2011-10-19

    The focus of this study was on the assessment of technology that might be of clinical utility in identification, quantification, characterization of carbonylation in human plasma proteins. Carbonylation is widely associated with oxidative stress diseases. Breast cancer patient samples were chosen as a stress positive case based on the fact that oxidative stress has been reported to be elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that breast cancer patients in this study were indeed experiencing significant oxidative stress. Carbonyl groups in proteins from freshly drawn blood were derivatized with biotin hydrazide after which the samples were dialyzed and the biotinylated proteins subsequently selected, digested and labeled with iTRAQ™ heavy isotope coding reagent(s). Four hundred sixty proteins were identified and quantified, 95 of which changed 1.5 fold or more in concentration. Beyond confirming the utility of the analytical method, association of protein carbonylation was examined as well. Nearly one fourth of the selected proteins were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by unbiased knowledge assembly methods indicated the most likely disease associated with the proteins was breast neoplasm. Pathway analysis showed the proteins which changed in carbonylation were strongly associated with Brca1, the breast cancer type-1 susceptibility protein. Pathway analysis indicated the major molecular functions of these proteins are defense, immunity and nucleic acid binding. PMID:21856457

  11. Oxidative stress induced carbonylation in human plasma

    PubMed Central

    Madian, Ashraf G.; Diaz-Maldonado, Naomi; Gao, Qiang; Regnier, Fred E.

    2011-01-01

    The focus of this study was on the assessment of technology that might be of clinical utility in identification, quantification, characterization of carbonylation in human plasma proteins. Carbonylation is widely associated with oxidative stress diseases. Breast cancer patient samples were chosen as a stress positive case based on the fact that oxidative stress has been reported to be elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that breast cancer patients in this study were indeed experiencing significant oxidative stress. Carbonyl groups in proteins from freshly drawn blood were derivatized with biotin hydrazide after which the samples were dialyzed and the biotinylated proteins subsequently selected, digested and labeled with iTRAQ™ heavy isotope coding reagent(s). Four hundred sixty proteins were identified and quantified, 95 of which changed 1.5 fold or more in concentration. Beyond confirming the utility of the analytical method, association of protein carbonylation was examined as well. Nearly one fourth of the selected proteins were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by unbiased knowledge assembly methods indicated the most likely disease associated with the proteins was breast neoplasm. Pathway analysis showed the proteins which changed in carbonylation were strongly associated with Brca1, the breast cancer type-1 susceptibility protein. Pathway analysis indicated the major molecular functions of these proteins are defense, immunity and nucleic acid binding. PMID:21856457

  12. 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

  13. 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. PMID:26463138

  14. Bovine Serum Albumin-Catalyzed Deprotonation of [1-13C]-Glycolaldehyde: Protein Reactivity Toward Deprotonation of α–Hydroxy α–Carbonyl Carbon

    PubMed Central

    Go, Maybelle K.; Malabanan, M. Merced; Amyes, Tina L.; Richard, John P.

    2010-01-01

    Bovine serum albumin (BSA) in D2O at 25 °C and pD 7.0 was found to catalyze the deuterium exchange reactions of [1-13C]-glycolaldehyde ([1-13C]-GA) to form [1-13C, 2-2H]-GA and [1-13C, 2,2-di-2H]-GA. The formation of [1-13C, 2-2H]-GA and [1-13C, 2,2-di-2H]-GA in a total yield of 51 ± 3% was observed at early reaction times, and at latter times [1-13C, 2-2H]-GA was observed to undergo BSA-catalyzed conversion to [1-13C, 2,2-di-2H]-GA. The overall second-order rate constant for these deuterium exchange reactions is (kE)P = 0.25 M−1 s−1. By comparison, values of (kE)P = 0.04 M−1 s−1 (Go, M. K., Amyes, T. L., and Richard, J. P. (2009), Biochemistry 48, 5769–5778) and 0.06 M−1 s−1 (Go, M. K., Koudelka, A., Amyes, T. L., and Richard, J. P. (2010), Biochemistry 49, 5377–5389) have been determined, respectively, for the wildtype- and K12G mutant TIM-catalyzed deuterium exchange reactions of [1-13C]-GA to form [1-13C, 2,2-di-2H]-GA. These data show that TIM and BSA exhibit a modest catalytic activity towards deprotonation of α-hydroxy α-carbonyl carbon. It is suggested that this activity is intrinsic to many globular proteins, and that it must be enhanced to demonstrate successful de novo design of protein catalysts of reactions through enamine intermediates. PMID:20687575

  15. 2-Aminoadipic acid is a marker of protein carbonyl oxidation in the aging human skin: effects of diabetes, renal failure and sepsis

    PubMed Central

    Sell, David R.; Strauch, Christopher M.; Shen, Wei; Monnier, Vincent M.

    2007-01-01

    We hypothesized that the ϵ-amino group of lysine residues in longlived proteins oxidatively deaminates with age forming the carbonyl compound, allysine (α-aminoadipic acid-δ-semialdehyde), which can further oxidize into 2-aminoadipic acid. In the present study, we measured both products in insoluble human skin collagen from n=117 individuals of age range 10–90 years, of which n=61 and n=56 were non-diabetic and diabetic respectively, and a total of n=61 individuals had either acute or chronic renal failure. Allysine was reduced by borohydride into 6-hydroxynorleucine and both products were measured in acid hydrolysates by selective ion monitoring gas chromatography (GC)-MS. The results showed that 2-aminoadipic acid (P<0.0001), but not 6-hydroxynorleucine (P=0.14), significantly increased with age reaching levels of 1 and 0.3 mmol/mol lysine at late age respectively. Diabetes in the absence of renal failure significantly (P<0.0001) increased 2-aminoadipic acid up to <3 mmol/mol, but not 6-hydroxynorleucine (levels<0.4 mmol/mol, P=0.18). Renal failure even in the absence of diabetes markedly increased levels reaching up to <0.5 and 8 mmol/mol for 6-hydroxynorleucine and 2-aminoadipic acid respectively. Septicaemia significantly (P<0.0001) elevated 2-aminoadipic acid in non-diabetic, but not diabetic individuals, and mildly correlated with other glycoxidation markers, carboxymethyl-lysine and the methylglyoxal-derived products, carboxyethyl-lysine, argpyrimidine and MODIC (methylglyoxal-derived imidazolium cross-link). These results provide support for the presence of metal-catalysed oxidation (the Suyama pathway) in diabetes and the possible activation of myeloperoxidase during sepsis. We conclude that 2-aminoadipic acid is a more reliable marker for protein oxidation than its precursor, allysine. Its mechanism of formation in each of these conditions needs to be elucidated. PMID:17313367

  16. 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.

  17. 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

  18. AGE-DEPENDENT CHANGES IN ACTIVITY OF MALLARD PLASMA CHOLINESTERASES

    EPA Science Inventory

    Plasma acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activity was measured repeatedly in 27 mallard (Anas platyrhynchos) ducklings between 7 and 85 days of age to determine age-dependent changes in enzyme activity. Plasma AChE, BChe, and total cholinesterase (ChE) a...

  19. 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

  20. Age-dependent cognitive impairment in a Drosophila Fragile X model and its pharmacological rescue

    PubMed Central

    Choi, Catherine H.; Schoenfeld, Brian P.; Liebelt, David A.; Ferreiro, David; Ferrick, Neal J.; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L.; Terlizzi, Allison M.; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T.; Bell, Aaron J.; McDonald, Thomas V.

    2010-01-01

    Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms. PMID:20039205

  1. 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

  2. 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

  3. A SIRS epidemic model with infection-age dependence

    NASA Astrophysics Data System (ADS)

    Zhang, Zhonghua; Peng, Jigen

    2007-07-01

    Based on J. Mena-Lorca and H.W. Hethcote's epidemic model, a SIRS epidemic model with infection-age-dependent infectivity and general nonlinear contact rate is formulated. Under general conditions, the unique existence of its global positive solutions is obtained. Moreover, under more general assumptions than the existing, the existence and asymptotical stability of its equilibria are discussed. In the end, the condition on the stability of endemic equilibrium is verified by a special model.

  4. 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

  5. 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

  6. Anomalous scaling in an age-dependent branching model

    NASA Astrophysics Data System (ADS)

    Keller-Schmidt, Stephanie; Tuǧrul, 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.

  7. Age-dependent social learning in a lizard

    PubMed Central

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

    2014-01-01

    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. PMID:25009244

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. The role of HSP70 in mediating age-dependent mortality in sepsis

    PubMed Central

    McConnell, Kevin W.; Fox, Amy C.; Clark, Andrew T.; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A.; Farris, Alton B.; Buchman, Timothy G.; Hunt, Clayton R.; Coopersmith, Craig M.

    2011-01-01

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6–12week old) and aged (16–17 month old) HSP70−/− and wild type (WT) mice to determine if HSP70 modulated outcome in an age-dependent fashion. Young HSP70−/− and WT mice subjected to cecal ligation and puncture (CLP), Pseudomonas aeruginosa pneumonia or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70−/− mice than aged WT mice subjected to CLP (p=0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared to WT mice, aged septic HSP70−/− mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70−/−mice had increased systemic levels of TNF-α, IL-6, IL-10 and IL-1β compared to WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977

  1. Age dependence of natural uranium and thorium concentrations in bone.

    PubMed

    Larivière, Dominic; Packer, Ana Paula; Marro, Leonora; Li, Chunsheng; Chen, Jing; Cornett, R Jack

    2007-02-01

    The age dependence of the natural concentration of uranium and thorium in the skeleton was investigated using human vertebrae bone collected from two Canadian locations (Winnipeg, Manitoba, and Regina, Saskatchewan). The concentration of both radioelements in digested ashed bone samples was determined using sector-field inductively coupled plasma mass spectrometry. The geometric means for uranium level in bones showed a significant statistical difference between the two locations studied. Similarly for thorium, a statistical difference was observed, although this difference was considered marginal. The thorium concentration differed only marginally with respect to age group, indicating that its behavior in the body could be age-independent. Conversely, the uranium level in bones was found to change for the age groups tested, an indication of age-specific deposition. The age profile for uranium was comparable to the calcium turn-over rate, indicating that uranium deposition is probably, in part, dictated by this metabolic process, showing the role of present uptake into the uranium concentration in bones for populations exposed to significant uranium intake. PMID:17220713

  2. 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

  3. 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.

  4. The probiotic mixture IRT5 ameliorates age-dependent colitis in rats.

    PubMed

    Jeong, Jin-Ju; Woo, Jae-Yeon; Ahn, Young-Tae; Shim, Jae-Hun; Huh, Chul-Sung; Im, Sin-Heog; Han, Myung Joo; Kim, Dong-Hyun

    2015-06-01

    To investigate the anti-inflammatory effect of probiotics, we orally administered IRT5 (1×10(9)CFU/rat) for 8 weeks to aged (16 months-old) Fischer 344 rats, and measured parameters of colitis. The expression levels of the inflammatory markers' inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were higher in the colons of normal aged rats (18 months-old) than in the colons of normal young rats (6 months-old). Treatment with IRT5 suppressed the age-associated increased expression of iNOS, COX2, TNF-α, and IL-1β, and activation of NF-κB and mitogen-activated protein kinases. In a similar manner, the expression of tight junction proteins in the colon of normal aged rats was suppressed more potently than in normal young rats, and treatment of aged rats with IRT5 decreased the age-dependent suppression of tight junction proteins ZO-1, occludin, and claudin-1. Treatment with IRT5 suppressed age-associated increases in expressions of senescence markers p16 and p53 in the colon of aged rats, but increased age-suppressed expression of SIRT1. However, treatment with IRT5 inhibited age-associated increased myeloperoxidase activity in the colon. In addition, treatment with IRT5 lowered the levels of LPS in intestinal fluid and blood of aged rats, as well as the reduced concentrations of reactive oxygen species, malondialdehyde, and C-reactive protein in the blood. These findings suggest that IRT5 treatment may suppress age-dependent colitis by inhibiting gut microbiota LPS production. PMID:25907245

  5. Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent.

    PubMed

    Podlasek, Carol A; Ghosh, Rudrani; Onur Cakir, Omer; Bond, Christopher; McKenna, Kevin E; McVary, Kevin T

    2013-11-01

    Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n=39). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. PMID:23872662

  6. 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.

  7. 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

  8. 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.

  9. 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

  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 change in urine proteome of healthy individuals

    NASA Astrophysics Data System (ADS)

    Dobrokhotov, Igor; Liudmila Pastushkova, MRS.; Larina, Irina; Kononikhin, Alexey

    It was analyzed the protein composition of urine samples obtained from twenty Russian cosmonauts and thirty-eight healthy volunteers, that have been selected for the experiments simulating the physiological effects of microgravity. The special sample preparation was performed, followed by liquid chromatography-mass spectrometry. Liquid chromatography-mass spectrometry of the minor proteins was performed on a nano-HPLC Agilent 1100 system (Agilent Technologies Inc., USA) in combination with a LTQ-FT Ultra mass spectrometer (Thermo Electron, Germany). List of masses derived peptides and they fragments have used for search and identification of proteins by database IPI-human (international index of protein) using the program Mascot (MS version 2.0.04 , UK) according to the following criteria: 1 - enzyme-trypsin; 2 - peptide tol. ± 5 ppm; 3 - MS / MS tol. 0.5Da. From list of proteins obtained as a result Mascot-search it was selected only those proteins that were identified based on 2 or more peptides with the rating more than 24. Analysis of the list of proteins was performed using software developed in the laboratory of VA Ivanisenko (ICG SB RAS) Age of healthy individuals was ranged from 18 to 54 years. Depending on the age, the data were divided into three groups: those relating to the group of persons under 25 years (youth and mature age 1), 25-40 years (mature age 2) and 40-54 years (mature age 3) It was detected reliable changes in the number of proteins among groups depending of the age. It was found that the minimum number of different proteins were detected in the urine of the group of young patients (under 25 years old) , and the maximum - was observed in the group of middle-aged persons (25 to 40 years). When the proteins were compared according to their molecular mass it was revealed that in the older group (40-54 years ) there is noticeably smaller percentage of high molecular weight proteins than in groups of young and middle aged persons. Thus

  12. 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

  13. Estrogen Effects on Vascular Inflammation are Age-Dependent: Role of Estrogen Receptors

    PubMed Central

    Kapadia, Akash; Chen, Yiu-Fai; Szalai, Alexander J.; Oparil, Suzanne; Hage, Fadi G.

    2014-01-01

    Objective 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones carried out in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age-dependent. Approach and Results Young (10-wk) and aged (52-wk) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pre-treatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pre-treatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER)-knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ERα and in VSMCs via ERβ. BMMs derived from aged (vs. young) mice expressed significantly less ERα mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice. Conclusions E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ERα expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age-dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women. PMID:24876352

  14. 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

  15. Pharmacological and genetic reversal of age dependent cognitive deficits due to decreased presenilin function

    PubMed Central

    McBride, Sean M. J.; Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Liebelt, David A.; Ferreiro, David; Choi, Richard J.; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M.; Ferrick, Neal J.; Koenigsberg, Eric; Rudominer, Rebecca L.; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K.; Nguyen, Hanh T.; Fortini, Mark E.; McDonald, Thomas V.; Jongens, Thomas A.

    2010-01-01

    Alzheimer's disease is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are due to mutations in a single copy of the Presenilin (PS) and Amyloid Precursor Protein (APP) genes. The dominant inheritance pattern of FAD indicates that it may be due to gain or change of function mutations. Studies of FAD-linked forms of presenilin in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of DmGluRA, the inositol trisphosphate receptor (InsP3R) or IPPase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP3R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced. PMID:20631179

  16. αβγ-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction

    PubMed Central

    Greten-Harrison, Becket; Polydoro, Manuela; Morimoto-Tomita, Megumi; Diao, Ling; Williams, Andrew M.; Nie, Esther H.; Makani, Sachin; Tian, Ning; Castillo, Pablo E.; Buchman, Vladimir L.; Chandra, Sreeganga S.

    2010-01-01

    Synucleins are a vertebrate-specific family of abundant neuronal proteins. They comprise three closely related members, α-, β-, and γ-synuclein. α-Synuclein has been the focus of intense attention since mutations in it were identified as a cause for familial Parkinson's disease. Despite their disease relevance, the normal physiological function of synucleins has remained elusive. To address this, we generated and characterized αβγ-synuclein knockout mice, which lack all members of this protein family. Deletion of synucleins causes alterations in synaptic structure and transmission, age-dependent neuronal dysfunction, as well as diminished survival. Abrogation of synuclein expression decreased excitatory synapse size by ∼30% both in vivo and in vitro, revealing that synucleins are important determinants of presynaptic terminal size. Young synuclein null mice show improved basic transmission, whereas older mice show a pronounced decrement. The late onset phenotypes in synuclein null mice were not due to a loss of synapses or neurons but rather reflect specific changes in synaptic protein composition and axonal structure. Our results demonstrate that synucleins contribute importantly to the long-term operation of the nervous system and that alterations in their physiological function could contribute to the development of Parkinson's disease. PMID:20974939

  17. Age-Dependent Labeling and Imaging of Insulin Secretory Granules

    PubMed Central

    Ivanova, Anna; Kalaidzidis, Yannis; Dirkx, Ronald; Sarov, Mihail; Gerlach, Michael; Schroth-Diez, Britta; Müller, Andreas; Liu, Yanmei; Andree, Cordula; Mulligan, Bernard; Münster, Carla; Kurth, Thomas; Bickle, Marc; Speier, Stephan; Anastassiadis, Konstantinos; Solimena, Michele

    2013-01-01

    Insulin is stored within the secretory granules of pancreatic β-cells, and impairment of its release is the hallmark of type 2 diabetes. Preferential exocytosis of newly synthesized insulin suggests that granule aging is a key factor influencing insulin secretion. Here, we illustrate a technology that enables the study of granule aging in insulinoma cells and β-cells of knock-in mice through the conditional and unequivocal labeling of insulin fused to the SNAP tag. This approach, which overcomes the limits encountered with previous strategies based on radiolabeling or fluorescence timer proteins, allowed us to formally demonstrate the preferential release of newly synthesized insulin and reveal that the motility of cortical granules significantly changes over time. Exploitation of this approach may enable the identification of molecular signatures associated with granule aging and unravel possible alterations of granule turnover in diabetic β-cells. Furthermore, the method is of general interest for the study of membrane traffic and aging. PMID:23929935

  18. Age-dependent labeling and imaging of insulin secretory granules.

    PubMed

    Ivanova, Anna; Kalaidzidis, Yannis; Dirkx, Ronald; Sarov, Mihail; Gerlach, Michael; Schroth-Diez, Britta; Müller, Andreas; Liu, Yanmei; Andree, Cordula; Mulligan, Bernard; Münster, Carla; Kurth, Thomas; Bickle, Marc; Speier, Stephan; Anastassiadis, Konstantinos; Solimena, Michele

    2013-11-01

    Insulin is stored within the secretory granules of pancreatic β-cells, and impairment of its release is the hallmark of type 2 diabetes. Preferential exocytosis of newly synthesized insulin suggests that granule aging is a key factor influencing insulin secretion. Here, we illustrate a technology that enables the study of granule aging in insulinoma cells and β-cells of knock-in mice through the conditional and unequivocal labeling of insulin fused to the SNAP tag. This approach, which overcomes the limits encountered with previous strategies based on radiolabeling or fluorescence timer proteins, allowed us to formally demonstrate the preferential release of newly synthesized insulin and reveal that the motility of cortical granules significantly changes over time. Exploitation of this approach may enable the identification of molecular signatures associated with granule aging and unravel possible alterations of granule turnover in diabetic β-cells. Furthermore, the method is of general interest for the study of membrane traffic and aging. PMID:23929935

  19. 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

  20. LINC00507 Is Specifically Expressed in the Primate Cortex and Has Age-Dependent Expression Patterns.

    PubMed

    Mills, James D; Ward, Melanie; Chen, Bei Jun; Iyer, Anand M; Aronica, Eleonora; Janitz, Michael

    2016-08-01

    Over the past decade, there has been an increase in the appreciation of the role of non-coding RNA in the development of organism phenotype. It is possible to divide the non-coding elements of the transcriptome into three categories: short non-coding RNAs, circular RNAs and long non-coding RNAs. Long non-coding RNAs are those transcripts that are greater than 200 nts in length and lack any significant open reading frames that produce proteins greater then 100 amino acids. Long intervening non-coding RNAs (lincRNAs) are a subclass of long non-coding RNAs. In contrast to protein coding RNAs, lincRNAs are expressed in a more tissue- and species-specific manner. In particular, many lincRNAs are only conserved amongst higher primates. This coupled with the propensity of many lincRNAs to be expressed in the brain, suggests that they are in fact one of the major drivers of organism complexity. We analysed 39 lincRNAs that are expressed in the frontal cortex and identified LINC00507 as being expressed in a cortex-specific manner in non-human primates and humans. The expression patterns of LINC00507 appear to be age-dependent, suggesting it may be involved in brain development of higher primates. Moreover, the analysis of LINC00507 potential to bind ribosomes revealed that this previously identified non-coding transcript may harbour a micropeptide. PMID:27059230

  1. Age dependent levels of plasma homocysteine and cognitive performance.

    PubMed

    Agrawal, Aruna; Ilango, K; Singh, Praveen K; Karmakar, Dipankar; Singh, G P I; Kumari, Rinki; Dubey, G P

    2015-04-15

    Elevated plasma homocysteine (hcy) levels, also known as hyperhomocysteinemia (hhcy), have been associated with cognitive impairment and neurodegenerative disorders. Hhcy has been attributed to deficiency of B vitamins which can adversely affect the brain and result in memory loss and poor attention power. Monitoring hcy levels and the use of vitamin supplementation to treat hhcy may therefore prove advantageous for the prevention and management of cognitive impairment. With this in consideration, we measured plasma hcy, folate and vitamin B12 levels in 639 subjects from different age groups in two sub-regions of India. Cognitive function was also measured using attention span and immediate and delayed memory recall tests. Depression scores were obtained using the Beck Depression Inventory-II and functional impairment was assessed using the functional activities questionnaire (FAQ) score. As hhcy has also been linked to inflammation, plasma levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were also measured. The results demonstrated significant negative correlations between hcy levels and folic acid levels, vitamin B12 levels and cognitive performance (attention span and delayed but not immediate memory recall) along with significant positive correlations between hcy levels and depression scores and hsCRP (but not IL-6) levels. A positive correlation was also observed between hcy levels and FAQ scores, however this was not found to be significant. Based on these results, folic acid and vitamin B12 intervention in people with elevated hcy levels in India could prove to be effective in lowering hcy levels and help maintain or improve cognitive function. PMID:25601573

  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. 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

  6. 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.

  7. 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. PMID:26433933

  8. 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

  9. Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice

    PubMed Central

    Domenighetti, Andrea A.; Chu, Pao-Hsien; Wu, Tongbin; Sheikh, Farah; Gokhin, David S.; Guo, Ling T.; Cui, Ziyou; Peter, Angela K.; Christodoulou, Danos C.; Parfenov, Michael G.; Gorham, Joshua M.; Li, Daniel Y.; Banerjee, Indroneal; Lai, Xianyin; Witzmann, Frank A.; Seidman, Christine E.; Seidman, Jonathan G.; Gomes, Aldrin V.; Shelton, G. Diane; Lieber, Richard L.; Chen, Ju

    2014-01-01

    Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery–Dreifuss muscular dystrophy. However, it remains to be clarified whether mutations in FHL1 cause skeletal muscle remodeling owing to gain- or loss of FHL1 function. In this study, we used FHL1-null mice lacking global FHL1 expression to evaluate loss-of-function effects on skeletal muscle homeostasis. Histological and functional analyses of soleus, tibialis anterior and sternohyoideus muscles demonstrated that FHL1-null mice develop an age-dependent myopathy associated with myofibrillar and intermyofibrillar (mitochondrial and sarcoplasmic reticulum) disorganization, impaired muscle oxidative capacity and increased autophagic activity. A longitudinal study established decreased survival rates in FHL1-null mice, associated with age-dependent impairment of muscle contractile function and a significantly lower exercise capacity. Analysis of primary myoblasts isolated from FHL1-null muscles demonstrated early muscle fiber differentiation and maturation defects, which could be rescued by re-expression of the FHL1A isoform, highlighting that FHL1A is necessary for proper muscle fiber differentiation and maturation in vitro. Overall, our data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations. PMID:23975679

  10. 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

  11. 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

  12. 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

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

    PubMed Central

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

    2015-01-01

    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

  14. Aging-dependent changes in rat heart mitochondrial glutaredoxins--Implications for redox regulation.

    PubMed

    Gao, Xing-Huang; Qanungo, Suparna; Pai, Harish V; Starke, David W; Steller, Kelly M; Fujioka, Hisashi; Lesnefsky, Edward J; Kerner, Janos; Rosca, Mariana G; Hoppel, Charles L; Mieyal, John J

    2013-01-01

    Clinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1) and concomitant decrease in NF-κB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS). In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50-60% in the IMS, but Grx2 is increased by 1.4-2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron-sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron-sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ. PMID:25126518

  15. 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

  16. 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

  17. Age-dependence of lipid parameters in the general population and vegetarians.

    PubMed

    Richter, V; Rassoul, F; Hentschel, B; Kothe, K; Krobara, M; Unger, R; Purschwitz, K; Rotzsch, W; Thiery, J; Muradian, K

    2004-06-01

    Age-dependent changes of lipid metabolism may arise both as a result of mechanisms of biological ageing and factors influencing age-dependent changes. To study possible influences of nutrition and life-style of vegetarians on age-dependence of lipid parameters, subjects of general population were compared with vegetarians. In the frame of population-based lipid screening projects in the city of Leipzig/Germany (Lipid Study Leipzig, LSL) 10 550 subjects (3,816 men and 6,734 women, age 18-99 years) of general population were compared with 417 vegetarians (vegans, lacto-vegetarians, lacto-ovo-vegetarians, 148 men and 269 women, age 18-93 years). Most of the vegetarians included in the study were members of the German Society of Vegetarians. The study program included capillary blood cholesterol measurements and the determination of high-density lipoprotein (HDL)-cholesterol, the measurement of other cardiovascular risk factors and the evaluation of dietary and life-style factors. Evaluation of cardiovascular risk profile within LSL was connected with individual consultation. The mean total cholesterol and non-HDL-cholesterol level and the total: HDL-cholesterol ratio showed the expected age-dependence, with maximum values within the decade 60-70 years. Vegetarians showed lower total and non-HDL-cholesterol levels in comparison with the general population. Furthermore, the age-dependent increase of these parameters is less pronounced under the conditions of vegetarian nutrition and life-style. Especially in young adulthood a significant difference is observed. Thus, the results of the present study reveal the role of nutritional and life-style factors that determine the lipid profile on a population basis and suggest that the known age-dependent rise of the level of atherogenic plasma lipoproteins is partly preventable. PMID:15224241

  18. Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons

    PubMed Central

    Cho, Kyoung-in; Yi, Haiqing; Yeh, Andrew; Tserentsoodol, Nomingerel; Cuadrado, Lori; Searle, Kelly; Hao, Ying; Ferreira, Paulo A.

    2008-01-01

    Prolonged light exposure is a determinant factor in inducing neurodegeneration of photoreceptors by apoptosis. Yet, the molecular bases of the pathways and components triggering this cell death event are elusive. Here, we reveal a prominent age-dependent increase in the susceptibility of photoreceptor neurons to undergo apoptosis under light in a mouse model. This is accompanied by light-induced subcellular changes of photoreceptors, such as dilation of the disks at the tip of the outer segments, prominent vesiculation of nascent disks, and autophagy of mitochondria into large multilamellar bodies. Notably, haploinsufficiency of Ran-binding protein-2 (RanBP2) suppresses apoptosis and most facets of membrane dysgenesis observed with age upon light-elicited stress. RanBP2 haploinsufficiency promotes decreased levels of free fatty acids in the retina independent of light exposure and turns the mice refractory to weight gain on a high-fat diet, whereas light promotes an increase in hydrogen peroxide regardless of the genotype. These studies demonstrate the presence of age-dependent and RanBP2-mediated pathways modulating membrane biogenesis of the outer segments and light-elicited neurodegeneration of photoreceptors. Furthermore, the findings support a mechanism whereby the RanBP2-dependent production of free fatty acids, metabolites thereof or the modulation of a cofactor dependent on any of these, promote apoptosis of photoreceptors in concert with the light-stimulated production of reactive oxygen species. PMID:18949001

  19. 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

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26563579

  1. AGE-DEPENDENT DIFFERENCES IN THE SUSCEPTIBILITY OF RATS TO DELTAMETHRIN

    EPA Science Inventory

    Separate groups of weanling and adult rats were exposed to both behaviorally-active and lethal doses of deltamethrin to examine age-dependent toxicity of a pyrethroid over a wide dose range. he acoustic startle response (ASR) was selected for comparison at low doses since it is a...

  2. 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…

  3. 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.

  4. 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. PMID:23784073

  5. AGE DEPENDENT MODEL OF PCB IN A LAKE MICHIGAN FOOD CHAIN

    EPA Science Inventory

    An age-dependent food chain model that considers species bioenergetics and toxicant exposure through water and food was developed. It was successfully applied to PCB contamination in the Lake Michigan lake trout food chain represented by phytoplankton, Mysis, alewife, and lake tr...

  6. 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…

  7. Age-dependent modulation of the somatosensory network upon eye closure.

    PubMed

    Brodoehl, Stefan; Klingner, Carsten; Witte, Otto W

    2016-02-01

    Eye closure even in complete darkness can improve somatosensory perception by switching the brain to a uni-sensory processing mode. This causes an increased information flow between the thalamus and the somatosensory cortex while decreasing modulation by the visual cortex. Previous work suggests that these modulations are age-dependent and that the benefit in somatosensory performance due to eye closing diminishes with age. The cause of this age-dependency and to what extent somatosensory processing is involved remains unclear. Therefore, we intended to characterize the underlying age-dependent modifications in the interaction and connectivity of different sensory networks caused by eye closure. We performed functional MR-imaging with tactile stimulation of the right hand under the conditions of opened and closed eyes in healthy young and elderly participants. Conditional Granger causality analysis was performed to assess the somatosensory and visual networks, including the thalamus. Independent of age, eye closure improved the information transfer from the thalamus to and within the somatosensory cortex. However, beyond that, we found an age-dependent recruitment strategy. Whereas young participants were characterized by an optimized information flow within the relays of the somatosensory network, elderly participants revealed a stronger modulatory influence of the visual network upon the somatosensory cortex. Our results demonstrate that the modulation of the somatosensory and visual networks by eye closure diminishes with age and that the dominance of the visual system is more pronounced in the aging brain. PMID:26546882

  8. Structural Basis for Substrate Specificity in Human Monomeric Carbonyl Reductases

    PubMed Central

    El-Hawari, Yasser; Dunford, James E.; Kochan, Grazyna; Wsol, Vladimir; Martin, Hans-Joerg; Maser, Edmund; Oppermann, Udo

    2009-01-01

    Carbonyl reduction constitutes a phase I reaction for many xenobiotics and is carried out in mammals mainly by members of two protein families, namely aldo-keto reductases and short-chain dehydrogenases/reductases. In addition to their capacity to reduce xenobiotics, several of the enzymes act on endogenous compounds such as steroids or eicosanoids. One of the major carbonyl reducing enzymes found in humans is carbonyl reductase 1 (CBR1) with a very broad substrate spectrum. A paralog, carbonyl reductase 3 (CBR3) has about 70% sequence identity and has not been sufficiently characterized to date. Screening of a focused xenobiotic compound library revealed that CBR3 has narrower substrate specificity and acts on several orthoquinones, as well as isatin or the anticancer drug oracin. To further investigate structure-activity relationships between these enzymes we crystallized CBR3, performed substrate docking, site-directed mutagenesis and compared its kinetic features to CBR1. Despite high sequence similarities, the active sites differ in shape and surface properties. The data reveal that the differences in substrate specificity are largely due to a short segment of a substrate binding loop comprising critical residues Trp229/Pro230, Ala235/Asp236 as well as part of the active site formed by Met141/Gln142 in CBR1 and CBR3, respectively. The data suggest a minor role in xenobiotic metabolism for CBR3. Enhanced version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. PMID:19841672

  9. Palladium-catalyzed oxidative carbonylation reactions.

    PubMed

    Wu, Xiao-Feng; Neumann, Helfried; Beller, Matthias

    2013-02-01

    Palladium-catalyzed coupling reactions have become a powerful tool for advanced organic synthesis. This type of reaction is of significant value for the preparation of pharmaceuticals, agrochemicals, as well as advanced materials. Both, academic as well as industrial laboratories continuously investigate new applications of the different methodologies. Clearly, this area constitutes one of the major topics in homogeneous catalysis and organic synthesis. Among the different palladium-catalyzed coupling reactions, several carbonylations have been developed and widely used in organic syntheses and are even applied in the pharmaceutical industry on ton-scale. Furthermore, methodologies such as the carbonylative Suzuki and Sonogashira reactions allow for the preparation of interesting building blocks, which can be easily refined further on. Although carbonylative coupling reactions of aryl halides have been well established, palladium-catalyzed oxidative carbonylation reactions are also interesting. Compared with the reactions of aryl halides, oxidative carbonylation reactions offer an interesting pathway. The oxidative addition step could be potentially avoided in oxidative reactions, but only few reviews exist in this area. In this Minireview, we summarize the recent development in the oxidative carbonylation reactions. PMID:23307763

  10. 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

  11. Stratospheric carbonyl sulfide (OCS) burden

    NASA Astrophysics Data System (ADS)

    Kloss, Corinna; Walker, Kaley A.; Deshler, Terry; von Hobe, Marc

    2015-04-01

    An estimation of the global stratospheric burden of carbonyl sulfide (OCS) calculated using satellite based measurements from the Atmospheric Chemistry Experiment - Fourier Transform Spectrometer (ACE-FTS) will be presented. OCS is the most abundant sulfur containing gas in the atmosphere in the absence of volcanic eruptions. With a long lifetime of 2-6 years it reaches the stratosphere where it is photolyzed and the sulfur oxidized and condensed to aerosols, contributing to the stratospheric aerosol layer. The aerosol layer is the one factor of the middle-atmosphere with a direct impact on the Earth's climate by scattering incoming solar radiation back to space. Therefore it is crucial to understand and estimate the different processes and abundances of the species contributing to the aerosol layer. However, the exact amount of OCS in the stratosphere has not been quantified yet. A study on the OCS mixing ratio distribution based on ACE-FTS data has already been made by Barkley et al. (2008), also giving an estimation for the total atmospheric OCS mass. ACE-FTS is an infrared solar occultation spectrometer providing high- resolution profile observations since 2004. In the scope of this work the focus lies on the stratospheric OCS burden, calculated by integrating the ACE profiles. A global overview on the stratospheric OCS amount in the past and present based on the ACE data as well as a look at regional and seasonal variability will be given. Furthermore, the results of this work will be useful for further studies on OCS fluxes and lifetimes, and in quantifying the contribution of OCS to the global stratospheric sulfur burden. Barkley et al., 2008, Geophys. Res. Lett., 35, L14810.

  12. Proteomic and Carbonylation Profile Analysis of Rat Skeletal Muscles following Acute Swimming Exercise

    PubMed Central

    Pietrovito, Laura; Fiaschi, Tania; Bini, Luca; Esposito, Fabio; Marini, Marina; Abruzzo, Provvidenza Maria; Gulisano, Massimo; Modesti, Alessandra

    2013-01-01

    Previous studies by us and other groups characterized protein expression variation following long-term moderate training, whereas the effects of single bursts of exercise are less known. Making use of a proteomic approach, we investigated the effects of acute swimming exercise (ASE) on protein expression and carbonylation patterns in two hind limb muscles: the Extensor Digitorum Longus (EDL) and the Soleus, mostly composed of fast-twitch and slow-twitch fibres, respectively. Carbonylation is one of the most common oxidative modifications of proteins and a marker of oxidative stress. In fact, several studies suggest that physical activity and the consequent increase in oxygen consumption can lead to increase in reactive oxygen and nitrogen species (RONS) production, hence the interest in examining the impact of RONS on skeletal muscle proteins following ASE. Results indicate that protein expression is unaffected by ASE in both muscle types. Unexpectedly, the protein carbonylation level was reduced following ASE. In particular, the analysis found 31 and 5 spots, in Soleus and EDL muscles respectively, whose carbonylation is reduced after ASE. Lipid peroxidation levels in Soleus were markedly reduced as well. Most of the decarbonylated proteins are involved either in the regulation of muscle contractions or in the regulation of energy metabolism. A number of hypotheses may be advanced to account for such results, which will be addressed in future studies. PMID:23967250

  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. Plasma Protein Oxidation and Its Correlation with Antioxidant Potential During Human Aging

    PubMed Central

    Pandey, Kanti Bhooshan; Mehdi, Mohd Murtaza; Maurya, Pawan Kumar; Rizvi, Syed Ibrahim

    2010-01-01

    Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins. PMID:20826915

  16. 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

  17. Age dependence of metals in hair in a selected US population

    SciTech Connect

    Paschal, D.C.; DiPietro, E.S.; Phillips, D.L.; Gunter, E.W. )

    1989-02-01

    Concentrations of 28 metals were determined in hair samples from 199 children (age {le} years) and 322 adults (age 13-73) years. Levels of calcium, barium, magnesium, zinc, and strontium all show a similar age-dependent increase up to about 12-14 years; levels of aluminum show a decrease with age. Relationships of elemental concentrations with age were examined by using correlation, linear regression, t tests, and discriminant analysis. Statistically significant differences in mean concentration values between children and adults were shown for these metals. Discriminant analysis gave about 95% accuracy in classifying a test data set into the categories of children and adults. A hypothesis suggested by the data is that there is an age-dependent excretion in hair of alkali metals during skeletal growth and development. The observed decrease in aluminum is largely unexplained at this time.

  18. Influence of nootropic drugs on the age-dependent potassium-coupling of transmitter release.

    PubMed

    Wustmann, C; Blaschke, M; Rudolph, E; Fischer, H D; Schmidt, J

    1990-01-01

    The potassium-induced dopamine release from rat striatum slices shows an age-dependent decline comparable to observations after hypoxia. Pretreatment of aged animals with antihypoxically active nootropic drugs for three weeks results in an improvement of the impaired transmitter release. Simultaneously the slope of the stimulus-release relation is increased and an age-related 50% decrease of the high affinity Ca(++)-ATPase activity (brain P2 fraction) is partially compensated. Like the antihypoxic effect, the effectiveness of nootropic drugs regarding age-dependent changes of neuronal functions probably will consist, above all, in vascular influences of the microcirculation, repair of phospholipids damaged by free radical triggered peroxidation and improvement of stimulus-release coupling. PMID:2149265

  19. 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

  20. Fast photolysis of carbonyl nitrates from isoprene

    NASA Astrophysics Data System (ADS)

    Müller, Jean-Francois; Peeters, Jozef; Stavrakou, Trisevgeni

    2014-05-01

    We show that photolysis is, by far, the major atmospheric sink of isoprene-derived carbonyl nitrates. Empirical evidence from published laboratory studies on the absorption cross sections and photolysis rates of α-nitrooxy ketones suggests that the presence of the nitrate group (i) greatly enhances the absorption cross sections, and (ii) facilitates dissociation to a point that the photolysis quantum yield is close to unity, with O-NO2 dissociation as the likely major channel. On this basis, we provide new recommendations for estimating the cross sections and photolysis rates of carbonyl nitrates. The newly estimated photorates are validated using a chemical box model against measured temporal profiles of carbonyl nitrates in an isoprene oxidation experiment by Paulot et al. (2009). The comparisons for ethanal nitrate and for the sum of methacrolein- and methylvinylketone nitrates strongly supports our assumptions of large cross section enhancements and a near-unit quantum yield for these compounds. These findings have significant atmospheric implications, as carbonyl nitrates constitute an important component of the total organic nitrate pool over vegetated areas: the photorates of key carbonyl nitrates from isoprene are estimated to be typically between ~3 and 20 times higher than their sink due to reaction with OH in relevant atmospheric conditions. Moreover, since the reaction is expected to release NO2, photolysis is especially effective in depleting the total organic nitrate pool.

  1. Process and catalyst for carbonylating olefins

    DOEpatents

    Zoeller, Joseph Robert

    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.

  2. 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.

  3. 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.

  4. Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function.

    PubMed

    Arda, H Efsun; Li, Lingyu; Tsai, Jennifer; Torre, Eduardo A; Rosli, Yenny; Peiris, Heshan; Spitale, Robert C; Dai, Chunhua; Gu, Xueying; Qu, Kun; Wang, Pei; Wang, Jing; Grompe, Markus; Scharfmann, Raphael; Snyder, Michael S; Bottino, Rita; Powers, Alvin C; Chang, Howard Y; Kim, Seung K

    2016-05-10

    Intensive efforts are focused on identifying regulators of human pancreatic islet cell growth and maturation to accelerate development of therapies for diabetes. After birth, islet cell growth and function are dynamically regulated; however, establishing these age-dependent changes in humans has been challenging. Here, we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. These profiles revealed distinct proliferative and functional states of islet α cells or β cells and histone modifications underlying age-dependent gene expression changes. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet β cells. SIX2 and SIX3 were sufficient to enhance insulin content or secretion in immature β cells. Our work provides a unique resource to study human-specific regulators of islet cell maturation and function. PMID:27133132

  5. 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.

  6. Mechanism of protein decarbonylation.

    PubMed

    Wong, Chi-Ming; Marcocci, Lucia; Das, Dividutta; Wang, Xinhong; Luo, Haibei; Zungu-Edmondson, Makhosazane; Suzuki, Yuichiro J

    2013-12-01

    Ligand/receptor stimulation of cells promotes protein carbonylation that is followed by the decarbonylation process, which might involve thiol-dependent reduction (C.M. Wong et al., Circ. Res. 102:301-318; 2008). This study further investigated the properties of this protein decarbonylation mechanism. We found that the thiol-mediated reduction of protein carbonyls is dependent on heat-labile biologic components. Cysteine and glutathione were efficient substrates for decarbonylation. Thiols decreased the protein carbonyl content, as detected by 2,4-dinitrophenylhydrazine, but not the levels of malondialdehyde or 4-hydroxynonenal protein adducts. Mass spectrometry identified proteins that undergo thiol-dependent decarbonylation, which include peroxiredoxins. Peroxiredoxin-2 and -6 were carbonylated and subsequently decarbonylated in response to the ligand/receptor stimulation of cells. siRNA knockdown of glutaredoxin inhibited the decarbonylation of peroxiredoxin. These results strengthen the concept that thiol-dependent decarbonylation defines the kinetics of protein carbonylation signaling. PMID:24044890

  7. 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

  8. Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart.

    PubMed

    Fuentes, Tania I; Appleby, Nancy; Raya, Michael; Bailey, Leonard; Hasaniya, Nahidh; Stodieck, Louis; Kearns-Jonker, Mary

    2015-01-01

    Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of

  9. 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

  10. Carbonyl extraction of lunar and asteroidal metals

    NASA Astrophysics Data System (ADS)

    Lewis, John S.; Jones, Thomas D.; Farrand, William H.

    It is suggested that the Mond process for carbonyl extraction of metals from ore may be used as an efficient, low-energy scheme for producing high-purity Fe, Ni, Cr, Mn, and Co from lunar or asteroidal feedstocks. It is proposed that scenarios for obtaining oxygen from the lunar relogith can be enhanced by carbonyl processing of the metallic alloy byproducts of such operations. It is further suggested that the native metal content of asteroidal regoliths is even more suitable to carbonyl processing. High-purity, corrosion-resistant Fe and Ni can be extracted from asteroidal feedstocks along with a Co-rich residue containing 0.5 percent platinum-group metals. Recommendations for bringing the method to a practical level of development for space applications are presented.

  11. 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

  12. Advances in Measurement of Carbonyls in Aerosols.

    NASA Astrophysics Data System (ADS)

    Charles, M.; Jakober, C.; Spaulding, R.; Green, P.; Destaillats, H.; Hughes, J. M.

    2002-12-01

    Chamber studies establish the formation of highly polar oxygenated species from the reaction of anthropogenic and biogenic hydrocarbons with hydroxyl radicals or ozone. A paucity of data exists however on the generation and fate of these organics in the ambient atmospheric environment. This is primarily due to the absence of suitable analytical methods. To address limitations of existing methods, we developed methods that rely on O-(2,3,4,5,6)-pentafluorobenzylhydroxylamine (PFBHA), and bis-(trimethylsilyl) trifluoroacetamide (BSTFA) in concert with GC/ion trap mass spectrometry (GC/ITMS) to identify and quantify carbonyl, dicarbonyl and hydroxy carbonyl photooxidation products in aerosols at part-per-trillion (pptv) levels. We also optimized and evaluated a mist chamber to sample carbonyls and multi-functional carbonyls with 10 minute sampling times. We applied the method to identify and quantify 2-hydroxy-2-methyl propanal (2-HMPR), a proposed photooxidation product of 2-methyl-3-buten-2-ol (MBO) in the Blodgett Forest, CA. The average 2-HMPR/MBO mixing ratio was 0.33ñ 0.25, which is reasonable since the expected yield of 2-HMPR from the hydroxyl radical oxidation of MBO is 0.19-0.35. Further method development in our laboratory is exploring the employment of HPLC/atmospheric pressure chemical ionization (APCI) mass spectra to identify model aliphatic and aromatic carbonyls (the major classes were aldehydes, ketones, dicarbonyls, and quinones) in aerosols. The data indicate the potential for pentafluorobenzyl derivatization in concert with GC/ITMS and HPLC/ITMS to measure a broad range of carbonyls.

  13. Palladium-catalyzed carbonylative synthesis of benzoxazinones from N-(o-bromoaryl)amides using paraformaldehyde as the carbonyl source.

    PubMed

    Li, Wanfang; Wu, Xiao-Feng

    2014-11-01

    Carbonylation reactions have been widely used in organic synthesis. However, the manipulation of toxic and pressurized carbon monoxide limited their applications in organic laboratories. The search for alternative carbonyl sources as an important method for carbonylative organic synthesis is spreading. Herein, a series of substituted benzoxazinones were synthesized from N-(o-bromoaryl)amides by palladium-catalyzed carbonylation with paraformaldehyde as the carbonyl source, which is inexpensive, stable, and easy to use. Notably, this is the first example of using paraformaldehyde as the CO source in palladium-catalyzed carbonylative synthesis of heterocycles. PMID:25280209

  14. Fast photolysis of carbonyl nitrates from isoprene

    NASA Astrophysics Data System (ADS)

    Müller, J.-F.; Peeters, J.; Stavrakou, T.

    2014-03-01

    Photolysis is shown to be a major sink for isoprene-derived carbonyl nitrates, which constitute an important component of the total organic nitrate pool over vegetated areas. Empirical evidence from published laboratory studies on the absorption cross sections and photolysis rates of α-nitrooxy ketones suggests that the presence of the nitrate group (i) greatly enhances the absorption cross sections and (ii) facilitates dissociation to a point that the photolysis quantum yield is close to unity, with O-NO2 dissociation as a likely major channel. On this basis, we provide new recommendations for estimating the cross sections and photolysis rates of carbonyl nitrates. The newly estimated photo rates are validated using a chemical box model against measured temporal profiles of carbonyl nitrates in an isoprene oxidation experiment by Paulot et al. (2009). The comparisons for ethanal nitrate and for the sum of methacrolein- and methyl vinyl ketone nitrates strongly supports our assumptions of large cross-section enhancements and a near-unit quantum yield for these compounds. These findings have significant atmospheric implications: the photorates of key carbonyl nitrates from isoprene are estimated to be typically between ~ 3 and 20 times higher than their sink due to reaction with OH in relevant atmospheric conditions. Moreover, since the reaction is expected to release NO2, photolysis is especially effective in depleting the total organic nitrate pool.

  15. Fast photolysis of carbonyl nitrates from isoprene

    NASA Astrophysics Data System (ADS)

    Müller, J.-F.; Peeters, J.; Stavrakou, T.

    2013-11-01

    Photolysis is shown to be a major sink for isoprene-derived carbonyl nitrates, which constitute an important component of the total organic nitrate pool over vegetated areas. Empirical evidence from published laboratory studies on the absorption cross sections and photolysis rates of α-nitrooxy ketones suggests that the presence of the nitrate group (i) greatly enhances the absorption cross sections, and (ii) facilitates dissociation to a point that the photolysis quantum yield is close to unity, with O-NO2 dissociation as the likely major channel. On this basis, we provide new recommendations for estimating the cross sections and photolysis rates of carbonyl nitrates. The newly estimated photorates are validated using a chemical box model against measured temporal profiles of carbonyl nitrates in an isoprene oxidation experiment by Paulot et al. (2009). The comparisons for ethanal nitrate and for the sum of methacrolein- and methylvinylketone nitrates strongly supports our assumptions of large cross section enhancements and a near-unit quantum yield for these compounds. These findings have significant atmospheric implications: the photorates of key carbonyl nitrates from isoprene are estimated to be typically between ~3 and 20 times higher than their sink due to reaction with OH in relevant atmospheric conditions. Moreover, since the reaction is expected to release NO2, photolysis is especially effective in depleting the total organic nitrate pool.

  16. Organocatalyzed Intramolecular Carbonyl-Ene Reactions.

    PubMed

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

    2016-01-01

    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. PMID:27258238

  17. 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)

  18. Polyimides Containing Carbonyl and Ether Connecting Groups

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M.; Havens, Stephen J.

    1987-01-01

    Semicrystallinity gives rise to tough, solvent-resistant polymers. New polyimides prepared from reaction of aromatic dianhydrides with new diamines containing carbonyl and ether connecting groups between aromatic rings. Damines prepared from reaction of 4-aminophenol with activated aromatic difluoro compounds in presence of potassium carbonate. These types of polymers have potential applications in molded products, films, adhesives, and composites.

  19. Age-Dependent Neuroimmune Modulation of IGF-1R in the Traumatic Mice

    PubMed Central

    2012-01-01

    Background Age-dependent neuroimmune modulation following traumatic stress is accompanied by discordant upregulation of Fyn signaling in the frontal cortex, but the mechanistic details of the potential cellular behavior regarding IGF-1R/Fyn have not been established. Methods Trans-synaptic IGF-1R signaling during the traumatic stress was comparably examined in wild type, Fyn (−/−) and MOR (−/−) mice. Techniques included primary neuron culture, in vitro kinase activity, immunoprecipitation, Western Blot, sucrose discontinuous centrifugation. Besides that, [3 H] incorporation was used to assay lymphocyte proliferation and NK cell activity. Results We demonstrate robust upregulation of synaptic Fyn activity following traumatic stress, with higher amplitude in 2-month mice than that in 1-year counterpart. We also established that the increased Fyn signaling is accompanied by its molecular connection with IGF-1R within the synaptic zone. Detained analysis using Fyn (−/−) and MOR (−/−) mice reveal that IGF-1R/Fyn signaling is governed to a large extent by mu opioid receptor (MOR), and with age-dependent manner; these signaling cascades played a central role in the modulation of lymphocyte proliferation and NK cell activity. Conclusions Our data argued for a pivotal role of synaptic IGF-1R/Fyn signaling controlled by MOR downstream signaling cascades were crucial for the age-dependent neuroimmune modulation following traumatic stress. The result here might present a new quality of synaptic cellular communication governing the stress like events and have significant potential for the development of therapeutic approaches designed to minimize the heightened vulnerability during aging. PMID:22640633

  20. Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain

    PubMed Central

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

    2015-01-01

    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. PMID:26019347

  1. 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.

  2. 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)

  3. 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.

  4. Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

    PubMed Central

    Zinnanti, William J.; Lazovic, Jelena; Housman, Cathy; LaNoue, Kathryn; O’Callaghan, James P.; Simpson, Ian; Woontner, Michael; Goodman, Stephen I.; Connor, James R.; Jacobs, Russell E.; Cheng, Keith C.

    2007-01-01

    Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I. PMID:17932566

  5. 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.

  6. Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I.

    PubMed

    Zinnanti, William J; Lazovic, Jelena; Housman, Cathy; LaNoue, Kathryn; O'Callaghan, James P; Simpson, Ian; Woontner, Michael; Goodman, Stephen I; Connor, James R; Jacobs, Russell E; Cheng, Keith C

    2007-11-01

    Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I. PMID:17932566

  7. Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in Fischer 344 Rats.

    PubMed

    Jeong, Jin-Ju; Kim, Kyung-Ah; Ahn, Young-Tae; Sim, Jae-Hun; Woo, Jae-Yeon; Huh, Chul-Sung; Kim, Dong-Hyun

    2015-09-01

    To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 (1 × 10(11) CFU/g of each strain), and investigated its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 × 10(10) CFU/rat/day), which was administered orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent increases of blood triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p < 0.05). KF treatment slightly, but not significantly, shortened the escape latency daily for 4 days. Oral administration of KF restored age-suppressed doublecortin and brain-derived neurotrophic factor expression in aged rats. Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation. PMID:25975611

  8. Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

    PubMed

    Tao, K; Ichikawa, J; Matsuki, N; Ikegaya, Y; Koyama, R

    2016-03-24

    Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function. PMID:26794590

  9. Age dependence of the chemical composition of stars in globular clusters

    NASA Astrophysics Data System (ADS)

    Kipper, T.

    An overview of recent investigations of the age dependence of the chemical composition of stars in globular clusters is presented. Attention is given to two contradictory hypotheses on the issue of cluster age and metallicity. According to Carney (1980), there is a metallicity-age dependence. According to Gratton (1985), all globular clusters are the same age - approximately 16 x 10 exp 9 years old. The metallicity of the most metal-abundant clusters is discussed. The Fe/H metallicity of the object 47 Tuc is determined to range from -1.1 to -0.4. The chemical homogeneity of clusters is examined. Spectral investigations of NGC 6752 stars from the main sequence up to the upper part of the giants' branch did not show Fe/H dispersion. The study by Cohen (1980) of the relative distribution of heavy elements in clusters of different metallicity show that in spite of the significant difference in Fe/H (up to 2.0 dex) the relative abundances are quite similar.

  10. REDOX RESPONSIVE TRANSCRIPTION FACTOR1 is involved in age-dependent and systemic stress signaling

    PubMed Central

    Matsuo, Mitsuhiro; Oelmüller, Ralf

    2015-01-01

    REDOX RESPONSIVE TRANSCRIPTION FACTOR1 (RRTF1) regulates redox homeostasis under stress, however the mechanism is mainly unknown. In a recent publication, we analyzed rrtf1 knockout (ko) and RRTF1 overexpressor lines of Arabidopsis thaliana and showed that RRTF1 plays a crucial role in reactive oxygen species (ROS) production. Ko line produces less and overexpressor lines constitutively high levels of ROS under stress, and the amount of ROS increases with increase in stress and the RRTF1 level in the plant. The transcription factor also activates systemic ROS signaling under stress.1 In this report, we show that RRTF1 exerts different roles in young and old leaves. While RRTF1 enhances defense responses to high light (HL) stress in young leaves, it induces senescence and chlorosis in older leaves. These findings suggest that RRTF1 and/or RRTF1-mediated ROS signaling induce stress responses in an age-dependent manner, and the age-dependent alteration in the RRTF1 function might be important for plants' acclimation to the stress environment. PMID:26479402

  11. 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

  12. RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer’s disease

    PubMed Central

    Wong, Helen; Levenga, Josien; Cain, Peter; Rothermel, Beverly; Klann, Eric

    2016-01-01

    Aging is the largest risk factor for Alzheimer’s disease (AD). Patients with Down syndrome (DS) develop symptoms consistent with early-onset AD, suggesting that overexpression of chromosome 21 genes such as Regulator of Calcineurin 1 (RCAN1) plays a role in AD pathogenesis. RCAN1 levels are increased in the brain of DS and AD patients but also in the human brain with normal aging. RCAN1 has been implicated in several neuronal functions, but whether its increased expression is correlative or causal in the aging-related progression of AD remains elusive. We show that brain-specific overexpression of the human RCAN1.1S isoform in mice promotes early age-dependent memory and synaptic plasticity deficits, tau pathology, and dysregulation of dynamin-related protein 1 (DRP1) activity associated with mitochondrial dysfunction and oxidative stress, reproducing key AD features. Based on these findings, we propose that chronic RCAN1 overexpression during aging alters DRP1-mediated mitochondrial fission and thus acts to promote AD-related progressive neurodegeneration. PMID:26497675

  13. 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. PMID:22170152

  14. 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

  15. Cerebrospinal fluid extracellular vesicles undergo age dependent declines and contain known and novel non-coding RNAs.

    PubMed

    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

  16. 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

  17. 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

  18. Oxidative carbonylation of amines to carbamates

    SciTech Connect

    Waller, F.J.

    1987-04-01

    Within the last several years, new technologies have appeared to replace phosgene for isocyanate manufacture. These include carbamate chemistries based upon dialkyl carbonate, reductive carbonylation of nitroaromatics, and oxidative carbonylation of amines. The carbamate ester can be handled safely and is reversibly cleaved to the isocyanate. The technology described here involves the preparation of both aliphatic and aromatic carbamates from an amine, alcohol, CO, oxidant, and a non-corrosive catalyst. The catalyst precursor is Pd(OAc){sub 2} and the oxidants are copper carboxylates or copper carboxylates and molecular oxygen. The latter represents a one-step carbamate synthesis with high catalyst activity, nearly quantitative conversions and alcohol selectivities greater than 90%. Operating temperatures and pressures are 80-110{degree}C and less than 500 psi, respectively. Experiments designed to probe the mechanism will be presented along with a discussion of novel (Cu(O{sub 2}CR){sub 2}){sub 2}R'NH{sub 2} complexes.

  19. Portable chemiluminescence detector for nickel carbonyl

    SciTech Connect

    Hikade, D.A.; Stedman, D.H.; Walega, J.G.

    1984-08-01

    This article describes a portable chemiluminescent detector for Ni(CO)/sub 4/ containing two innovative components, a self-contained carbon monoxide source which provides a greater degree of portability and a thermal differentiator to improve selectivity. The instrument is capable of measuring parts-per-billion levels of Ni(CO)/sub 4/, Fe(CO)/sub 5/, and NO. The instrument was used to measure carbonyl concentrations in the field and in cigarette smoke.

  20. 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

  1. 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

  2. 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

  3. Age-dependent changes in T cell homeostasis and SIV load in sooty mangabeys.

    PubMed

    Chakrabarti, L A; Lewin, S R; Zhang, L; Gettie, A; Luckay, A; Martin, L N; Skulsky, E; Ho, D D; Cheng-Mayer, C; Marx, P A

    2000-08-01

    Sooty mangabeys (Cercocebus atys) showed age-dependent changes in T cell regeneration. Younger animals had a high percentage of CD4+ CD45RA + T cells and a high concentration of T cell receptor excisional circles (TRECs) in peripheral blood, which indicated active thymopoiesis. In contrast, older animals had an increased T cell turnover, which suggested that most T cell production occurred in the periphery. In addition, the number of peripheral CD4+ T cells naturally decreased with age. Non-pathogenic SIVsm infection did not significantly change the T cell proliferation rate or the TREC concentration, though it did cause a moderate loss of peripheral CD4 + T cells. The viral load correlated negatively with age, which could be accounted for by the reduced availability of CD4 + target cells in older mangabeys. Thus, the number of susceptible target cells may be a limiting factor in natural SIV infection. PMID:11085578

  4. 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

  5. The Immp2l mutation causes age-dependent degeneration of cerebellar granule neurons prevented by antioxidant treatment.

    PubMed

    Liu, Chunlian; Li, Xue; Lu, Baisong

    2016-02-01

    Reactive oxygen species are implicated in age-associated neurodegeneration, although direct in vivo evidence is lacking. We recently showed that mice with a mutation in the Inner Mitochondrial Membrane Peptidase 2-like (Immp2l) gene had elevated levels of mitochondrial superoxide, impaired fertility and age-associated phenotypes, including kyphosis and ataxia. Here we show that ataxia and cerebellar hypoplasia occur in old mutant mice (> 16 months). Cerebellar granule neurons (CGNs) are significantly underrepresented; Purkinje cells and cells in the molecular layer are not affected. Treating mutant mice with the mitochondria-targeted antioxidant SkQ1 from 6 weeks to 21 months protected cerebellar granule neurons. Apoptotic granule neurons were observed in mutant mice but not in age-matched normal control mice or SkQ1-treated mice. Old mutant mice showed increased serum protein carbonyl content, cerebellar 4-hydroxynonenal (HNE), and nitrotyrosine modification compared to old normal control mice. SOD2 expression was increased in Purkinje cells but decreased in granule neurons of old mutant mice. Mitochondrial marker protein VDAC1 also was decreased in CGNs of old mutant mice, suggesting decreased mitochondrial number. SkQ1 treatment decreased HNE and nitrotyrosine modification, and restored SOD2 and VDAC1 expression in CGNs of old mutant mice. Neuronal expression of nitric oxide synthase was increased in cerebella of young mutant mice but decreased in old mutant mice. Our work provides evidence for a causal role of oxidative stress in neurodegeneration of Immp2l mutant mice. The Immp2l mutant mouse model could be valuable in elucidating the role of oxidative stress in age-associated neurodegeneration. PMID:26616244

  6. Carbonyl compounds generated from electronic cigarettes.

    PubMed

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

    2014-11-01

    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. PMID:25353061

  7. Carbonyl Compounds Generated from Electronic Cigarettes

    PubMed Central

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

    2014-01-01

    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. PMID:25353061

  8. Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

    PubMed

    Lafuente, A; Márquez, N; Piquero, S; Esquifino, A I

    1999-01-11

    Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent. PMID:10048746

  9. Age-dependent speciation can explain the shape of empirical phylogenies.

    PubMed

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

    2015-05-01

    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

  10. Is the metabolism of 25-hydroxyvitamin D3 age-dependent in dairy cows?

    PubMed

    Wilkens, Mirja R; Cohrs, Imke; Lifschitz, Adrian L; Fraser, David R; Olszewski, Katharina; Schröder, Bernd; Breves, Gerhard

    2013-07-01

    It has recently been demonstrated that prepartum administered 25-hydroxyvitamin D3 (25-OHD3) is a promising candidate to assist the maintenance of peripartal calcium homeostasis in dairy cows. Since the incidence of peripartal hypocalcemia and the reported beneficial effects of the treatment are both associated with the lactation number, we investigated pharmacokinetic aspects of 25-OHD3 related to the age of dairy cows. The daily oral administration of 3mg 25-OHD3 in rapeseed oil as well as a treatment with 4 and 6mg included in the feed during the last eight to ten days of gestation resulted in linear dosage- and age-dependent increases in plasma 25-OHD3. After parturition the administration was stopped and blood samples were taken to calculate the plasma half-life. Irrespective of the supplemented dosage, cows starting the 2nd lactation showed a significantly longer plasma half-life of 25-OHD3 than cows starting the 3rd or higher lactation. Age-dependent differences in the increase of plasma 25-OHD3 could already be found before parturition when calcium homeostasis was not yet significantly challenged. Additionally, no correlations between plasma half-life of 25-OHD3 and 1,25-dihydroxyvitamin D3, PTH or the bone resorption marker CrossLaps were observed after parturition. Thus we conclude that the influence of the lactation number on the pharmacokinetics of 25-OHD3 is related directly to the age of the cows. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID:23220546

  11. 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

  12. 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.

  13. 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

  14. Age-dependent chloride channel expression in skeletal muscle fibres of normal and HSALR myotonic mice

    PubMed Central

    DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

    2013-01-01

    We combine electrophysiological and optical techniques to investigate the role that the expression of chloride channels (ClC-1) plays on the age-dependent electrical properties of mammalian muscle fibres. To this end, we comparatively evaluate the magnitude and voltage dependence of chloride currents (ICl), as well as the resting resistance, in fibres isolated from control and human skeletal actin (HSA)LR mice (a model of myotonic dystrophy) of various ages. In control mice, the maximal peak chloride current ([peak-ICl]max) increases from −583 ± 126 to −956 ± 260 μA cm−2 (mean ± SD) between 3 and 6 weeks old. Instead, in 3-week-old HSALR mice, ICl are significantly smaller (−153 ± 33 μA cm−2) than in control mice, but after a long period of ∼14 weeks they reach statistically comparable values. Thus, the severe ClC-1 channelopathy in young HSALR animals is slowly reversed with aging. Frequency histograms of the maximal chloride conductance (gCl,max) in fibres of young HSALR animals are narrow and centred in low values; alternatively, those from older animals show broad distributions, centred at larger gCl,max values, compatible with mosaic expressions of ClC-1 channels. In fibres of both animal strains, optical data confirm the age-dependent increase in gCl, and additionally suggest that ClC-1 channels are evenly distributed between the sarcolemma and transverse tubular system membranes. Although gCl is significantly depressed in fibres of young HSALR mice, the resting membrane resistance (Rm) at −90 mV is only slightly larger than in control mice due to upregulation of a Rb-sensitive resting conductance (gK,IR). In adult animals, differences in Rm are negligible between fibres of both strains, and the contributions of gCl and gK,IR are less altered in HSALR animals. We surmise that while hyperexcitability in young HSALR mice can be readily explained on the basis of reduced gCl, myotonia in adult HSALR animals may be explained on the basis of a

  15. Infrared spectroscopy of mass-selected metal carbonyl cations

    NASA Astrophysics Data System (ADS)

    Ricks, A. M.; Reed, Z. E.; Duncan, M. A.

    2011-04-01

    Metal carbonyl cations of the form M(CO)n+ are produced in a molecular beam by laser vaporization in a pulsed nozzle source. These ions, and their corresponding rare gas atom "tagged" analogs, M(CO)n(RG)m+, are studied with mass-selected infrared photodissociation spectroscopy in the carbonyl stretching region and with density functional theory computations. The number of infrared-active bands, their frequency positions, and their relative intensities provide distinctive patterns allowing determination of the geometries and electronic structures of these complexes. Cobalt penta carbonyl and manganese hexacarbonyl cations are compared to isoelectronic iron pentacarbonyl and chromium hexacarbonyl neutrals. Gold and copper provide examples of "non-classical" carbonyls. Seven-coordinate carbonyls are explored for the vanadium group metal cations (V +, Nb + and Ta +), while uranium cations provide an example of an eight-coordinate carbonyl.

  16. BAC Transgenic Mice Expressing a Truncated Mutant Parkin Exhibit Age-dependent Hypokinetic Motor Deficits, Dopaminergic Neuron Degeneration, and Accumulation of Proteinase K-Resistant Alpha-Synuclein

    PubMed Central

    Lu, Xiao-Hong; Fleming, Sheila M.; Meurers, Bernhard; Ackerson, Larry C.; Mortazavi, Farzad; Lo, Victor; Hernandez, Daniela; Sulzer, David; Jackson, George R.; Maidment, Nigel T.; Chesselet, Marie-Francoise; Yang, X. William

    2009-01-01

    Summary Recessive mutations in parkin are the most common cause of familial early onset Parkinson's disease (PD). Recent studies suggest that certain parkin mutants may exert dominant toxic effects to cultured cells and such dominant toxicity can lead to progressive dopaminergic (DA) neuron degeneration in Drosophila. To explore whether mutant parkin could exert similar pathogenic effects to mammalian DA neurons in vivo, we developed a Bacterial Artificial Chromosome (BAC) transgenic mouse model expressing a C-terminal truncated human mutant parkin (Parkin-Q311X) in DA neurons driven by a dopamine transporter promoter. Parkin-Q311X mice exhibit multiple late-onset and progressive hypokinetic motor deficits. Stereological analyses reveal that the mutant mice develop age-dependent DA neuron degeneration in substantia nigra accompanied by a significant loss of DA neuron terminals in the striatum. Neurochemical analyses reveal a significant reduction of the striatal dopamine level in mutant mice, which is significantly correlated with their hypokinetic motor deficits. Finally, mutant Parkin-Q311X mice, but not wild-type controls, exhibit age-dependent accumulation of proteinase-K resistant endogenous α-synuclein in substantia nigra and co-localized with 3-nitrotyrosine, a marker for oxidative protein damage. Hence, our study provides the first mammalian genetic evidence that dominant toxicity of a parkin mutant is sufficient to elicit age-dependent hypokinetic motor deficits and DA neuron loss in vivo, and uncovers a causal relationship between dominant parkin toxicity and progressive α-synuclein accumulation in DA neurons. Our study underscores the need to further explore the putative link between parkin dominant toxicity and PD. PMID:19228951

  17. Chemoselective Intramolecular Carbonyl Ylide Formation through Electronically Differentiated Malonate Diesters.

    PubMed

    Nakhla, Mina C; Lee, Che-Wah; Wood, John L

    2015-12-01

    A method for chemoselective carbonyl ylide formation utilizing the Rh(II) catalyzed decomposition of electronically differentiated diazo malonates is disclosed. Treatment of ethyl, trifluoro ethyl diazo malonate with a Rh(II) catalyst selectively forms a carbonyl ylide from the relatively electron rich ethyl ester. This carbonyl ylide can be trapped by various alkynes giving highly functionalized oxabicyclic compounds in a chemo-, regio-, and diastereoselective fashion. PMID:26584509

  18. 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).

  19. A comparison of egocentric and allocentric age-dependent spatial learning in the beagle dog.

    PubMed

    Christie, Lori-Ann; Studzinski, Christa M; Araujo, Joseph A; Leung, Cleo S K; Ikeda-Douglas, Candace J; Head, Elizabeth; Cotman, Carl W; Milgram, Norton W

    2005-03-01

    Spatial discriminations can be performed using either egocentric information based on body position or allocentric information based on the position of landmarks in the environment. Beagle dogs ranging from 2 to 16 years of age were tested for their ability to learn a novel egocentric spatial discrimination task that used two identical blocks paired in three possible spatial positions (i.e. left, center and right). Dogs were rewarded for responding to an object furthest to either their left or right side. Therefore, when the center location was used, it was correct on half of the trials and incorrect on the other half. Upon successful acquisition of the task, the reward contingencies were reversed, and the dogs were rewarded for responding to the opposite side. A subset of dogs was also tested on an allocentric spatial discrimination task, landmark discrimination. Egocentric spatial reversal learning and allocentric discrimination learning both showed a significant age-dependent decline, while initial egocentric learning appeared to be age-insensitive. Intra-subject correlation analyses revealed a significant relationship between egocentric reversal learning and allocentric learning. However, the correlation only accounted for a small proportion of the variance, suggesting that although there might be some common mechanism underlying acquisition of the two tasks, additional unique neural substrates were involved depending on whether allocentric or egocentric spatial information processing was required. PMID:15795044

  20. Age-dependent responses to chemosensory cues mediating kin recognition in dogs (Canis familiaris)

    PubMed

    Mekosh-Rosenbaum, V; Carr, W J; Goodwin, J L; Thomas, P L; D'Ver, A; Wysocki, C J

    1994-03-01

    During individually administered 5-min tests conducted in a neutral cage, four age groups (n = 10 males and 10 females per group) of purebred beagles reacted to bedding from their home cage vs. bedding from another litter of the same age. The 20-24-day-old males and females preferred (p < 0.05) home cage bedding over strange cage bedding. Those aged 31-36 days or 66-72 days showed no reliable preference for either type of bedding. Among pups aged 52-56 days, the males preferred (p < 0.05) strange cage bedding, but the females showed no reliable preference. Chemosensory cues are sufficient as mediators of kin recognition in beagles, but their reactions to such cues vary with age-dependent factors, some stemming from changes in the strength of the mother-litter bond. The dogs providing the two types of bedding lived in the same room and on the same diet. Therefore, kin recognition could not have been mediated by different chemosensory cues produced by variations in these environmental factors. PMID:8190767

  1. Cognitive experience and its effect on age-dependent cognitive decline in beagle dogs.

    PubMed

    Milgram, Norton W

    2003-11-01

    Test-sophisticated beagle dogs show marked age sensitivity in a size discrimination learning task, with old and senior dogs performing significantly more poorly than young dogs. By contrast, age differences in learning were not seen in dogs naive with respect to neuropsychological test experience. These results indicate that old animals benefit less from prior cognitive experience than young animals, which is an example of an age-dependent loss in plasticity. This finding also suggests that behaviorally experienced animals are a more useful model of human cognitive aging than behaviorally naïve animals. We also looked at the effect of a program of behavioral enrichment in aged dogs. One year of enrichment did not lead to significant differences, but after 2 years the behaviorally enriched group performed significantly better than the control group. The effect after 2 years indicates that a prolonged program of cognitive enrichment can serve as an effective intervention in aged dogs. These findings demonstrate that cognitive abilities in aged animals can be modified by providing behavioral experience, indicating that cognitive abilities remain moderately plastic, even in very old animals. PMID:14584821

  2. Age-Dependent Decline of Endogenous Pain Control: Exploring the Effect of Expectation and Depression

    PubMed Central

    Grashorn, Wiebke; Sprenger, Christian; Forkmann, Katarina; Wrobel, Nathalie; Bingel, Ulrike

    2013-01-01

    Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM) paradigms. In this study we investigated (i) the influence of age on CPM and (ii) the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20–40 years, middle-aged = 41–60 years, old = 61–80 years) were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS) and immersion of the contralateral foot into ice water as the conditioning stimulus (CS). The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age. PMID:24086595

  3. 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

  4. 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.

  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. Age-Dependent Demethylation of Sod2 Promoter in the Mouse Femoral Artery

    PubMed Central

    Nguyen, Albert; Leblond, François; Mamarbachi, Maya; Geoffroy, Steve; Thorin, Eric

    2016-01-01

    We studied the age-dependent regulation of the expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD encoded by Sod2) through promoter methylation. C57Bl/6 mice were either (i) sedentary (SED), (ii) treated with the antioxidant catechin (CAT), or (iii) voluntarily exercised (EX) from weaning (1-month old; mo) to 9 mo. Then, all mice aged sedentarily and were untreated until 12 mo. Sod2 promoter methylation was similar in all groups in 9 mo but decreased (p < 0.05) in 12 mo SED mice only, which was associated with an increased (p < 0.05) transcriptional activity in vitro. At all ages, femoral artery endothelial function was maintained; this was due to an increased (p < 0.05) contribution of eNOS-derived NO in 12 mo SED mice only. CAT and EX prevented these changes in age-related endothelial function. Thus, a ROS-dependent epigenetic positive regulation of Sod2 gene expression likely represents a defense mechanism prolonging eNOS function in aging mouse femoral arteries. PMID:26989455

  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. PMID:24468330

  8. 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. PMID:25666161

  9. 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

  10. Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice

    PubMed Central

    Yokoyama, Tadafumi; Yoshizaki, Ayumi; Simon, Karen L.; Kirby, Martha R.; Anderson, Stacie M.; Candotti, Fabio

    2015-01-01

    The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg) obtained from Was gene knockout (WKO) mice and found that their numbers were significantly lower in these mice compared to wild type (WT) controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS. PMID:26448644

  11. 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

  12. 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

  13. 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

  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. PMID:27537082

  15. Effect of pulsed electromagnetic fields on proteoglycan biosynthesis of articular cartilage is age dependent

    PubMed Central

    Bobacz, K; Graninger, W B; Amoyo, L; Smolen, J S

    2006-01-01

    Objective To investigate the effects of a pulsed electromagnetic field (EMF) on articular cartilage matrix biosynthesis with regard to age and cartilage damage using a matrix depleted cartilage explant model. Methods Cartilage explants were obtained from metacarpophalangeal joints of calves and adult cows. After depletion of the extracellular matrix by trypsin digestion, samples were maintained in serum‐free basal medium with and without the addition of interleukin 1β (IL1β). Half the samples were subjected to an EMF for 24 minutes daily; the other half were left untreated. Undigested and untreated explants served as negative controls. After 7 days, biosynthesis of matrix macromolecules was assessed by [35S]sulphate incorporation and values were normalised to hydroxyproline content. Results The EMF increased matrix macromolecule synthesis in undigested, untreated explants (p<0.009). In matrix depleted samples the EMF had no stimulatory effect on proteoglycan biosynthesis. IL1β significantly decreased the de novo synthesis of matrix macromolecules (p<0.00004) in young and adult samples, but an EMF partly counteracted this inhibitory effect in cartilage samples from young, but not old animals. Conclusion EMF promoted matrix macromolecule biosynthesis in intact tissue explants but had no stimulatory effect on damaged articular cartilage. The supressive effects of IL1β were partially counteracted by EMF exposure, exclusively in cartilage derived from young animals. An EMF has age dependent chondroprotective but not structure modifying properties when cartilage integrity is compromised. PMID:16769781

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

    PubMed

    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

    2016-05-01

    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

  17. 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

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

    PubMed

    Parks, N J; Keane, A T

    1983-01-01

    This paper examines in humans the proposition emanating from studies in beagles that initial retention of radium varies in proportion to the calcium addition rate at the time of intake. 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 15000 days following a series of therapeutic injections of 226Ra in humans ranging in age from 18 to 63 yr. The fractional retention R at t days following a single injection of 226Ra was described by R = (1 + t/d)-0.44. The age-dependent parameter d in the retention function was found to be proportional to the calcium addition rate at the time of injection in subjects receiving less than 200 micrograms 226Ra. PMID:6862890

  19. 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

  20. Age-dependent neonatal intracerebral hemorrhage in plasminogen activator inhibitor 1 knockout mice.

    PubMed

    Leroux, Philippe; Omouendze, Priscilla L; Roy, Vincent; Dourmap, Nathalie; Gonzalez, Bruno J; Brasse-Lagnel, Carole; Carmeliet, Peter; Leroux-Nicollet, Isabelle; Marret, Stéphane

    2014-05-01

    Intracerebral-intraventricular hemorrhages (ICH/IVH) in very preterm neonates are responsible for high mortality and subsequent disabilities. In humans, tissue plasminogen activator (t-PA) initiates fibrinolysis and activates endoluminal-endothelial receptors; dysfunction of the t-PA inhibitor (PAI-1) results in recurrent hemorrhages. We used PAI-1 knockout (PAI-1) mice to examine the role of t-PA in age-dependent intracranial hemorrhages as a possible model of preterm ICH/IVH. Intracortical injection of 2 μL of phosphate-buffered saline produced a small traumatic injury and a high rate of hemorrhage in PAI-1 pups at postnatal day 3 (P3) or P5, whereas it had no effect in wild-type neonates. This resulted in white matter and cortical lesions, ventricle enlargement, hyperlocomotion, and altered cortical levels of serotonin and dopamine in the adult PAI mice. N-methyl-D-aspartate receptor blockers, plasmin- and matrix metalloproteinases inhibitors reduced hemorrhage and tissue lesions. In contrast to P3 to P5, no significant hemorrhages were induced in P10 PAI-1 pups and there were no behavioral or neurochemical alterations in adulthood. These data suggest that microvascular immaturity up to P5 in mice is a determinant factor required for t-PA-dependent vascular rupture. Neonatal PAI-1 mice could be a useful ICH/IVH model for studying the ontogenic window of vascular immaturity and vascular protection against later neurodisabilities. PMID:24709679

  1. Age-dependent Homeostatic Plasticity of GABAergic Signaling in Developing Retinal Networks

    PubMed Central

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

    2013-01-01

    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 GABAA antagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4–P6, when GABAA signaling is depolarizing in ganglion cells, and at P7–P10, when GABAA 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 GABAA signaling. PMID:21865458

  2. Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans.

    PubMed

    Wagner, R; Heni, M; Linder, K; Ketterer, C; Peter, A; Böhm, A; Hatziagelaki, E; Stefan, N; Staiger, H; Häring, H-U; Fritsche, A

    2014-02-01

    The dopamine agonist bromocriptine has been approved for the treatment of type 2 diabetes in the United States. Bromocriptine inhibits prolactin secretion, and patients with hyperprolactinaemia display impaired insulin sensitivity. We therefore hypothesized that low prolactin levels are associated with lower glycaemia and higher insulin sensitivity in healthy subjects. Prolactin levels were determined from fasting serum in participants without diabetes from the cross-sectional Tübingen family study for type 2 diabetes (m/f = 562/1,121, age = 40 ± 13 years, BMI = 30 ± 9 kg/m(2)). A 75 g oral glucose tolerance test was performed, and the area under the glucose curve (AUC(0-120)Glucose) and insulin sensitivity index were calculated. A subgroup (n = 494) underwent hyperinsulinaemic-euglycaemic clamp tests. Prolactin associated positively with insulin sensitivity (p = 0.001, adjusted for gender, age, and BMI). Age strongly interacted (p < 0.0001) with the effect of prolactin on insulin sensitivity, inverting the positive relationship to a negative one in younger participants. Glycated haemoglobin (HbA1c) and AUC(0-120)Glucose correlated negatively with prolactin, and an interaction with age was found as well. Higher prolactin levels are associated with improved insulin sensitivity and lower glucose in individuals without diabetes. This relationship turns to its opposite in younger persons. As prolactin is a proxy for the dopaminergic tone in the central nervous system, these associations may indicate an age-dependent influence of the brain on peripheral insulin sensitivity. PMID:23836327

  3. 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. PMID:27074508

  4. Cytoprotective Effects of Hydrophilic and Lipophilic Extracts of Pistacia vera against Oxidative Versus Carbonyl Stress in Rat Hepatocytes.

    PubMed

    Shahraki, Jafar; Zareh, Mona; Kamalinejad, Mohammad; Pourahmad, Jalal

    2014-01-01

    This study was conducted to evaluate the cytoprotection of various extracts and bioactive compounds found in Pistacia vera againts cytotoxicity, ROS formation, lipid peroxidation, protein carbonylation, mitochondrial and lysosomal membrane damages in cell toxicity models of diabetes related carbonyl (glyoxal) and oxidative stress (hydroperoxide). Methanol, water and ethyl acetate were used to prepare crude pistachios extracts, which were then used to screen for in-vitro cytoprotection of freshly isolated rat hepatocytes against these toxins. The order of protection by Pistacia vera extracts against both hydroperoxide induced oxidative stress (ROS formation) and glyoxal induced protein carbonylation was: pistachio methanolic extract >pistachio water extract, gallic acid, catechin> α-tochoferol and pistachio ethyl acetate extract. Finally due to higher protection achieved by methanolic extract even compared to sole pretreatment of gallic acid, catechin or α-tochoferol, we suggest that cytoprotection depends on the variety of polar and non-polar compounds found in methanolic extract, it is likely that multiple cytoprotective mechanisms are acting against oxidative and carbonyl induced cytotoxicity. To our knowledge, we are the first to report the cytoprotective activity of Pistacia vera extracts against oxidative and carbonyl stress seen in type 2 diabetes hepatocytes model. PMID:25587316

  5. Cytoprotective Effects of Hydrophilic and Lipophilic Extracts of Pistacia vera against Oxidative Versus Carbonyl Stress in Rat Hepatocytes

    PubMed Central

    Shahraki, Jafar; Zareh, Mona; Kamalinejad, Mohammad; Pourahmad, Jalal

    2014-01-01

    This study was conducted to evaluate the cytoprotection of various extracts and bioactive compounds found in Pistacia vera againts cytotoxicity, ROS formation, lipid peroxidation, protein carbonylation, mitochondrial and lysosomal membrane damages in cell toxicity models of diabetes related carbonyl (glyoxal) and oxidative stress (hydroperoxide). Methanol, water and ethyl acetate were used to prepare crude pistachios extracts, which were then used to screen for in-vitro cytoprotection of freshly isolated rat hepatocytes against these toxins. The order of protection by Pistacia vera extracts against both hydroperoxide induced oxidative stress (ROS formation) and glyoxal induced protein carbonylation was: pistachio methanolic extract >pistachio water extract, gallic acid, catechin> α-tochoferol and pistachio ethyl acetate extract. Finally due to higher protection achieved by methanolic extract even compared to sole pretreatment of gallic acid, catechin or α-tochoferol, we suggest that cytoprotection depends on the variety of polar and non-polar compounds found in methanolic extract, it is likely that multiple cytoprotective mechanisms are acting against oxidative and carbonyl induced cytotoxicity. To our knowledge, we are the first to report the cytoprotective activity of Pistacia vera extracts against oxidative and carbonyl stress seen in type 2 diabetes hepatocytes model. PMID:25587316

  6. 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

  7. Age-Dependent Changes of the Temporal Order--Causes and Treatment.

    PubMed

    Gubin, Denis G; Weinert, Dietmar; Bolotnova, Tatyana V

    2016-01-01

    This review summarizes current knowledge on deteriorations in temporal order with advanced age. Changes of the overt rhythms will be described but also their putative causes and possible treatments of the disturbances. In aging animals and humans, all rhythm characteristics change. The most prominent changes are a decrease of circadian amplitude, leading to an extra-circadian dissemination (ECD), and a diminished ability to synchronize with the periodic environment. ECD is a shift from circadian to ultradian and infradian frequencies, accompanied by the loss of day-to-day phase stability. Responsiveness to photic and non-photic cues is decreased. As a consequence, both internal and external temporal order are disturbed not only under steady-state conditions but and even more markedly after changes in the periodic environment or following stressful events. Many of the changes seem to occur within the suprachiasmatic nucleus (SCN), the central circadian pacemaker, itself. The number of functioning neurons decreases with advancing age as does the coupling between them. Accordingly, the SCN generates a weaker and less stable circadian signal, insufficient to entrain peripheral oscillators properly or to regulate body functions rhythmically. However, age-dependent disturbances in peripheral organs must also be considered. These changes may occur at different ages, thus causing further internal desynchronization. Several possibilities exist with regard to treating circadian disruptions or at least minimizing their consequences for health and fitness and preventing sleep disturbances. Benefits of bright light, melatonin and other chronobiotics, physical activity, social contacts and regular feeding schedules in preserving the temporal order of aged organisms are discussed. PMID:26632427

  8. Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice.

    PubMed

    Xu, Heping; Chen, Mei; Manivannan, Ayyakkannu; Lois, Noemi; Forrester, John V

    2008-01-01

    Fundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal pigment epithelial (RPE) cells; however, direct clinicopathological correlation has not been possible in humans. We examined fundus AF by confocal scanning laser ophthalmoscopy and confocal microscopy in normal C57BL/6 mice of different ages. Increasingly strong AF signals were observed with age in the neuroretina and subretinal/RPE layer by confocal scanning laser ophthalmoscopy. Unlike fundus AF detected in normal human subjects, mouse fundus AF appeared as discrete foci distributed throughout the retina. Most of the AF signals in the neuroretina were distributed around retinal vessels. Confocal microscopy of retinal and choroid/RPE flat mounts demonstrated that most of the AF signals were derived from Iba-1+ perivascular and subretinal microglia. An age-dependent accumulation of Iba-1+ microglia at the subretinal space was observed. Lipofuscin granules were detected in large numbers in subretinal microglia by electron microscopy. The number of AF+ microglia and the amount of AF granules/cell increased with age. AF granules/lipofuscin were also observed in RPE cells in mice older than 12 months, but the number of AF+ RPE cells was very low (1.48 mm(-2) and 5.02 mm(-2) for 12 and 24 months, respectively) compared to the number of AF+ microglial cells (20.63 mm(-2) and 76.36 mm(-2) for 6 and 24 months, respectively). The fluorescence emission fingerprints of AF granules in subretinal microglia were the same as those in RPE cells. Our observation suggests that perivascular and subretinal microglia are the main cells producing lipofuscin in normal aged mouse retina and are responsible for in vivo fundus AF. Microglia may play an important role in retinal aging and age-related retinal diseases. PMID:17988243

  9. Age-dependent expression of the erythropoietin gene in rat liver and kidneys.

    PubMed Central

    Eckardt, K U; Ratcliffe, P J; Tan, C C; Bauer, C; Kurtz, A

    1992-01-01

    Using RNAse protection, we have made quantitative measurements of erythropoietin (EPO) mRNA in liver and kidneys of developing rats (days 1-54), to determine the relative contribution of both organs to the total EPO mRNA, to monitor changes which occur with development, and to compare the hypoxia-induced accumulation of EPO mRNA with the changes in serum EPO concentrations. To determine whether developmental and organ-specific responsiveness is related to the type of hypoxic stimulus, normobaric hypoxia was compared with exposure to carbon monoxide (functional anemia). Under both stimuli EPO mRNA concentration in liver was maximal on day 7 and declined during development. In contrast, EPO mRNA concentration in kidney increased during development from day 1 when it was 30-65% the hepatic concentration to day 54 when it was 12-fold higher than in liver. When organ weight was considered the liver was found to contain the majority of EPO mRNA in the first three to four weeks of life, and although, in stimulated animals, the hepatic proportion declined from 85-91% on day 1, it remained approximately 33% at day 54 and was similar for the two types of stimuli. When normalized for body weight the sum of renal and hepatic EPO mRNA in animals of a particular age was related linearly to serum hormone concentrations. However, the slope of this regression increased progressively with development, suggesting age-dependent alterations in translational efficiency or EPO metabolism. Images PMID:1541670

  10. 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

  11. 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

  12. Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

    PubMed Central

    2013-01-01

    Background The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence. Methods We evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11–12 month-old) rats. Results We did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry. Conclusions With a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of

  13. Age-Dependent Kinetics and Metabolism of Dichloroacetate: Possible Relevance to Toxicity

    PubMed Central

    Shroads, Albert L.; Guo, Xu; Dixit, Vaishali; Liu, Hui-Ping; James, Margaret O.; Stacpoole, Peter W.

    2008-01-01

    Dichloroacetate (DCA) is an investigational drug for certain metabolic diseases. It is biotransformed principally by the ζ-1 family isoform of glutathione transferase (GSTz1), also known as maleylacetoacetate isomerase (MAAI), which catalyzes the penultimate step in tyrosine catabolism. DCA causes a reversible peripheral neuropathy in several species, including humans. However, recent clinical trials indicate that adults are considerably more susceptible to this adverse effect than children. We evaluated the kinetics and biotransformation of DCA and its effects on tyrosine metabolism in nine patients treated for 6 months with 25 mg/kg/day and in rats treated for 5 days with 50 mg/kg/day. We also measured the activity and expression of hepatic GSTz1/MAAI. Chronic administration of DCA causes a striking age-dependent decrease in its plasma clearance and an increase in its plasma half-life in patients and rats. Urinary excretion of unchanged DCA in rats increases with age, whereas oxalate, an end product of DCA metabolism, shows the opposite trend. Low concentrations of monochloroacetate (MCA), which is known to be neurotoxic, increase as a function of age in the urine of dosed rats. MCA was detectable in plasma only of older animals. Hepatic GSTz1/MAAI-specific activity was inhibited equally by DCA treatment among all age groups, whereas plasma and urinary levels of maleylacetone, a natural substrate for this enzyme, increased with age. We conclude that age is an important variable in the in vivo metabolism and elimination of DCA and that it may account, in part, for the neurotoxicity of this compound in humans and other species. PMID:18096758

  14. 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

  15. 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

  16. Leptin is involved in age-dependent changes in response to systemic inflammation in the rat.

    PubMed

    Koenig, Sandy; Luheshi, Giamal N; Wenz, Tina; Gerstberger, Rüdiger; Roth, Joachim; Rummel, Christoph

    2014-02-01

    Obesity contributes to a state of subclinical peripheral and central inflammation and is often associated with aging. Here we investigated the source and contribution of adipose tissue derived cytokines and the cytokine-like hormone leptin to age-related changes in lipopolysaccharide (LPS)-induced brain-controlled sickness-responses. Old (24 months) and young (2 months) rats were challenged with LPS or saline alone or in combination with a neutralizing leptin antiserum (LAS) or control serum. Changes in the sickness-response were monitored by biotelemetry. Additionally, ex vivo fat-explants from young and old rats were stimulated with LPS or saline and culture medium collected and analyzed by cytokine-specific bioassays/ELISAs. We found enhanced duration/degree of the sickness-symptoms, including delayed but prolonged fever in old rats. This response was accompanied by increased plasma-levels of interleukin (IL)-6 and IL-1ra and exaggerated expression of inflammatory markers in brain and liver analyzed by RT-PCR including inhibitor κBα, microsomal prostaglandin synthase and cyclooxygenase 2 (brain). Moreover, for the first time, we were able to show prolonged elevated plasma leptin-levels in LPS-treated old animals. Treatment with LAS in young rats tended to attenuate the early- and in old rats the prolonged febrile response. Fat-explants exhibited unchanged IL-6 but reduced IL-1ra and tumor necrosis factor (TNF)-α release from adipose tissue of aged compared to young animals. In addition, we found increased expression of the endogenous immune regulator microRNA146a in aged animals suggesting a role for these mediators in counteracting brain inflammation. Overall, our results indicate a role of adipose tissue and leptin in “aging-related-inflammation” and age-dependent modifications of febrile-responses. PMID:24513873

  17. G-CSF enhances resolution of Staphylococcus aureus wound infection in an age-dependent manner.

    PubMed

    Brubaker, Aleah L; Kovacs, Elizabeth J

    2013-10-01

    This study tested the hypothesis that heightened bacterial colonization and delayed wound closure in aged mice could be attenuated by granulocyte colony-stimulating factor (G-CSF) treatment. Previously, we reported that aged mice had elevated bacterial levels, protracted wound closure, and reduced wound neutrophil accumulation after Staphylococcus aureus wound infection relative to young mice. In aseptic wound models, G-CSF treatment improved wound closure in aged mice to rates observed in young mice. Given these data, our objective was to determine if G-CSF could restore age-associated differences in wound bacterial burden and closure by increasing wound neutrophil recruitment. Young (3- to 4-month) and aged (18- to 20-month) BALB/c mice received three dorsal subcutaneous injections of G-CSF (250 ng/50 μL per injection) or saline control (50 μL per injection) 30 min after wound infection. Mice were killed at days 3 and 7 after wound infection, and bacterial colonization, wound size, wound leukocyte accumulation, and peripheral blood were evaluated. At days 3 and 7 after wound infection, bacterial colonization was significantly reduced in G-CSF-treated aged mice to levels observed in saline-treated young animals. Wound size was reduced in G-CSF-treated aged animals, with no effect on wound size in G-CSF-treated young mice. Local G-CSF treatment significantly enhanced neutrophil wound accumulation in aged mice, whereas there was no G-CSF-induced change in young mice. These data demonstrate that G-CSF enhances bacterial clearance and wound closure in an age-dependent manner. Moreover, G-CSF may be of therapeutic potential in the setting of postoperative wound infection or chronic nonhealing wounds in elderly patients. PMID:23856924

  18. 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.

  19. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

    PubMed

    Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott; Franti, Michael; Olwin, Bradley B; Bailey, Beth A; Rudnicki, Michael A; Houser, Steven R

    2016-04-01

    This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good. PMID:27034276

  20. 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.

  1. 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

  2. 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

  3. Age-dependent dichotomous effect of superoxide dismutase Ala16Val polymorphism on oxidized LDL levels

    PubMed Central

    Kanoni, Stavroula; Panagiotakos, Demosthenes B.; Louizou, Eirini; Grigoriou, Efi; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos

    2008-01-01

    We investigated the association between superoxide dismutase (SOD) Ala16Val polymorphism and the levels of oxidized LDL lipoprotein-C (ox-LDL-C) in two age-different Greek cohorts. Four hundred fifteen middle-aged (n = 147 females: 43.2 ± 13 years, n = 268 males: 43.3 ± 14 years) Caucasian Greek subjects consisted the middle aged cohort. One hundred seventy five elderly (n = 88 females: 79.9 ± 4 years; n = 87 males: 80.6 ± 4 years) were selected from the elderly cohort. Genotype data were obtained for all of them. Multiple linear regression analysis, stratified by gender and adjusted for age, smoking habits and body mass index as covariates, showed higher ox-LDL-C levels for the middle aged men with the Val/Val genotype, compared to the other allele (Ala/Ala and Ala/Val) carriers (65.9 ± 25.7 vs. 55.7 ± 20.5 mg/dl; standardized β coefficient = 0.192, P = 0.012). On the contrary, elderly women with the Val/Val genotype occurred with lower ox-LDL-C levels compared to the Ala/Ala or Ala/Val genotype (74.2 ± 22.1 vs. 86.5 ± 26.6 mg/dl; standardized β coefficient = -0.269, P = 0.015). The same trend was also recorded in elderly men, however without reaching statistical significance (standardized β coefficient = -0.187, P = 0.077). Moreover, elderly men and women with the Ala/Ala or Ala/Val genotype presented higher triglycerides levels compared to Val/Val (women: 145.2 ± 68.7 vs. 114.3 ± 34.3 mg/dl, P = 0.027; men: 147.8 ± 72.4 vs. 103.7 ± 38.0 mg/dl, P = 0.002). Additionally, middle aged men with the Val/Val genotype had higher HDL-C levels compared to the Ala allele carriers. The results suggest that SOD Ala16Val polymorphism is an age-dependent modulator of ox-LDL-C levels in middle-aged men and elderly women. PMID:18305395

  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. 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.

  6. Absorption of carbonyl sulfide in aqueous methyldiethanolamine

    SciTech Connect

    Al-Ghawas, H.A.; Ruiz-Ibanez, G.; Sandall, O.C. )

    1988-01-01

    The absorption of carbonyl sulfide in aqueous methyldiethanolamine (MDEA) was studied over a range of temperatures and MDEA concentrations. MDEA is commonly used for selective absorption of hydrogen sulfide in the presence of carbon dioxide. However, sulfur in the form of COS may also be present and it is necessary that estimates of absorption rates of this compound be made. The objective of this study is to determine the physiochemical properties needed to predict COS absorption rates in aqueous MDEA. Free gas solubility and the diffusivity of COS in MDEA solutions were measured over the temperature range 15 to 40{sup 0}C for MDEA concentrations up to 30 weight per cent using the nitrous oxide analogy method. Solubilities were measured volumetrically in an equilibrium cell and diffusivities were measured using a laminar liquid jet absorber. The kinetics of the reaction between COS and MDEA were studied by measuring absorption rates in a single wetted-sphere absorber.

  7. 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. PMID:25414135

  8. 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.

  9. 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%).

  10. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    PubMed Central

    Bruun, Camilla S; Jørgensen, Claus B; Bay, Lene; Cirera, Susanna; Jensen, Henrik E; Leifsson, Páll S; Nielsen, Jens; Christensen, Knud; Fredholm, Merete

    2008-01-01

    Background A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait. Results The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs. Conclusion A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular

  11. 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

  12. 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.

  13. 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.

  14. Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study.

    PubMed

    Colzani, Mara; De Maddis, Danilo; Casali, Gaia; Carini, Marina; Vistoli, Giulio; Aldini, Giancarlo

    2016-08-19

    Reactive carbonyl species (RCS) are endogenous or exogenous byproducts involved in the pathogenic mechanisms of different oxidative-based disorders. Detoxification of RCS by carbonyl quenchers is a promising therapeutic strategy. Among the most studied quenchers are aminoguanidine, hydralazine, pyridoxamine, and carnosine; their quenching activity towards four RCS (4-hydroxy-trans-2-nonenal, methylglyoxal, glyoxal, and malondialdehyde) was herein analyzed and compared. Their ability to prevent protein carbonylation was evaluated in vitro by using an innovative method based on high-resolution mass spectrometry (HRMS). The reactivity of the compounds was RCS dependent: carnosine efficiently quenched 4-hydroxy-trans-2-nonenal, pyridoxamine was particularly active towards malondialdehyde, aminoguanidine was active towards methylglyoxal and glyoxal, and hydralazine efficiently quenched all RCS. Reaction products were generated in vitro and were characterized by HRMS. Molecular modeling studies revealed that the reactivity was controlled by specific stereoelectronic parameters that could be used for the rational design of improved carbonyl quenchers. PMID:26891408

  15. 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 ...

  16. 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

  17. Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development

    PubMed Central

    Beheshti, Afshin; Wage, Justin; McDonald, J. Tyson; Lamont, Clare; Peluso, Michael; Hahnfeldt, Philip; Hlatky, Lynn

    2015-01-01

    The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease. PMID:26497558

  18. 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. PMID:26306813

  19. Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny.

    PubMed

    Hines, Ronald N; Simpson, Pippa M; McCarver, D Gail

    2016-07-01

    Human hepatic carboxylesterase 1 and 2 (CES1 and CES2) are important for the disposition of ester- and amide-bond-containing pharmaceuticals and environmental chemicals. CES1 and CES2 ontogeny has not been well characterized, causing difficulty in addressing concerns regarding juvenile sensitivity to adverse outcomes associated with exposure to certain substrates. To characterize postnatal human hepatic CES1 and CES2 expression, microsomal and cytosolic fractions were prepared using liver samples from subjects without liver disease (N = 165, aged 1 day to 18 years). Proteins were fractionated, detected, and quantitated by Western blotting. Median microsomal CES1 was lower among samples from subjects younger than 3 weeks (n = 36) compared with the rest of the population (n = 126; 6.27 vs. 17.5 pmol/mg microsomal protein, respectively; P < 0.001; Kruskal-Wallis test). Median cytosolic CES1 expression was lowest among samples from individuals between birth and 3 weeks of age (n = 36), markedly greater among those aged 3 weeks to 6 years (n = 90), and modestly greater still among those older than 6 years (n = 36; median values = 4.7, 15.8, and 16.6 pmol/mg cytosolic protein, respectively; P values < 0.001 and 0.05, respectively; Kruskal-Wallis test). Median microsomal CES2 expression increased across the same three age groups with median values of 1.8, 2.9, and 4.2 pmol/mg microsomal protein, respectively (P < 0.001, both). For cytosolic CES2, only the youngest age group differed from the two older groups (P < 0.001; median values = 1.29, 1.93, 2.0, respectively). These data suggest that infants younger than 3 weeks of age would exhibit significantly lower CES1- and CES2-dependent metabolic clearance compared with older individuals. PMID:26825642

  20. Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties.

    PubMed

    Horinouchi, Takahiro; Higashi, Tsunehito; Mazaki, Yuichi; Miwa, Soichi

    2016-01-01

    Cigarette mainstream smoke is composed of gas and tar phases and contains >4000 chemical constituents, including nicotine and tar. The substances in the gas phase but not in the tar phase can pass through the airway epithelial barrier, enter the systemic circulation via the pulmonary circulation, and increase systemic oxidative damage, leading to the development of cigarette smoking-related diseases such as atherosclerosis. Recently, we identified some stable carbonyl compounds, including acrolein (ACR) and methyl vinyl ketone (MVK), as major cytotoxic factors in nicotine- and tar-free cigarette smoke extract (CSE) of the gas phase. CSE, ACR, and MVK induce protein kinase C (PKC)-dependent activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and subsequent generation of reactive oxygen species (ROS) via NOX, causing plasma membrane damage and cell apoptosis. CSE, ACR, and MVK also trigger carbonylation of PKC, which is an irreversible oxidative modification. Cell damage and PKC carbonylation in response to treatment with CSE, ACR, or MVK are abolished by thiol-containing antioxidants such as N-acetyl-L-cysteine and reduced glutathione. Thus pharmacological modulation of PKC and NOX activities and the trapping of ROS are potential strategies for the prevention of diseases related to cigarette smoking. PMID:27251492

  1. MOLECULAR MECHANISM OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) INACTIVATION BY α,β-UNSATURATED CARBONYL DERIVATIVES

    PubMed Central

    Martyniuk, Christopher J.; Fang, Bin; Koomen, John M.; Gavin, Terrence; Zhang, Lihai; Barber, David S.; LoPachin, Richard M.

    2011-01-01

    α,β-Unsaturated carbonyls are an important class of chemicals involved in environmental toxicity and disease processes. Whereas adduction of cysteine residues on proteins is a well-documented reaction of these chemicals, such a generic effect cannot explain the molecular mechanism of cytotoxicity. Instead, more detailed information is needed regarding the possible specificity and kinetics of cysteine targeting and the quantitative relationship between adduct burden and protein dysfunction. To address these datagaps, purified human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was incubated with acrylamide (ACR), acrolein or methylvinyl ketone (MVK). Results show that these α,β-unsaturated carbonyl toxicants inhibited GAPDH activity in a concentration-and time-dependent manner. The rank order of enzyme inhibition (KI); i.e., ACR << MVK < acrolein, was related to the calculated electrophilic reactivity of each compound and to the corresponding kinetics of cysteine adduct formation. Tandem mass spectrometry revealed that adduct formation was selective at lower concentrations; i.e., ACR preferentially formed adducts with Cys152 (residues 146-162). At higher concentrations, ACR also formed adducts with Cys156 and Cys247 (residues 235-248). Adduct formation at Cys152 was correlated to enzyme inhibition, which is consistent with the regulatory role of this residue in enzyme function and its location within the GAPDH active site. Further analyses indicated that Cys152 was present in a pKa-lowering microenvironment (pKa = 6.03) and, at physiological pH, the corresponding sulfhydryl group exists in the highly reactive nucleophilic thiolate-state. These data suggest a general cytotoxic mechanism where electrophilic α,β-unsaturated carbonyls selectively form adducts with reactive nucleophilic cysteine residues specifically associated with the active sites of proteins. These specialized cysteine residues are toxicologically relevant molecular targets, since chemical

  2. Identification of carbonylated lipids from different phospholipid classes by shotgun and LC-MS lipidomics.

    PubMed

    Ni, Zhixu; Milic, Ivana; Fedorova, Maria

    2015-07-01

    Oxidized lipids play a significant role in the pathogenesis of numerous oxidative stress-related human disorders, such as atherosclerosis, obesity, inflammation, and autoimmune diseases. Lipid peroxidation, induced by reactive oxygen and nitrogen species, yields a high variety of modified lipids. Among them, carbonylated lipid peroxidation products (oxoLPP), formed by oxidation of the fatty acid moiety yielding aldehydes or ketones (carbonyl groups), are electrophilic compounds that are able to modify nucleophilic substrates like proteins, nucleic acid, and aminophospholipids. Some carbonylated phosphatidylcholines possess even pro-inflammatory activities. However, little is known about oxoLPP derived from other phospholipid (PL) classes. Here, we present a new analytical strategy based on the mass spectrometry (MS) of PL-oxoLPP derivatized with 7-(diethylamino)coumarin-3-carbohydrazide (CHH). Shotgun MS revealed many oxoLPP derived from in vitro oxidized glycerophosphatidylglycerols (PG, 31), glycerophosphatidylcholine (PC, 23), glycerophosphatidylethanolamine (PE, 34), glycerophosphatidylserines (PS, 7), glycerophosphatidic acids (PA, 17), and phosphatidylinositiolphosphates (PIP, 6) vesicles. This data were used to optimize LipidXplorer-assisted identification, and a python-based post-processing script was developed to increase both throughput and accuracy. When applied to full lipid extracts from rat primary cardiomyocytes treated with peroxynitrite donor SIN-1, ten PL-bound oxoLPP were unambiguously identified by LC-MS, including two PC-, two PE-, one PG-, two PS-, and three PA-derived species. Some of the well-known carbonylated PC were detected, while most PL-oxoLPP were shown for the first time. PMID:25701423

  3. Aldehyde dehydrogenase 2 activation in aged heart improves the autophagy by reducing the carbonyl modification on SIRT1.

    PubMed

    Wu, Bing; Yu, Lu; Wang, Yishi; Wang, Hongtao; Li, Chen; Yin, Yue; Yang, Jingrun; Wang, Zhifa; Zheng, Qiangsun; Ma, Heng

    2016-01-19

    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

  4. Infrared photodissociation spectroscopy of vanadium oxide-carbonyl cations.

    PubMed

    Brathwaite, A D; Ricks, A M; Duncan, M A

    2013-12-19

    Mass selected vanadium oxide-carbonyl cations of the form VO(m)(CO)(n)(+) (m = 0-3 and n = 3-6) are studied via infrared laser photodissociation spectroscopy in the 600-2300 cm(-1) region. Insight into the structure and bonding of these complexes is obtained from the number of infrared active bands, their relative intensities and their frequency positions. Density functional theory calculations are carried out in support of the experimental data. The effect of oxidation on the carbonyl stretching frequencies of VO(CO)(n)(+), VO2(CO)(n)(+), and VO3(CO)(n)(+) complexes is investigated. All of these oxide-carbonyl species have C-O stretch vibrations blue-shifted from those of the pure vanadium ion carbonyls. The V-O stretches of these complexes are also investigated, revealing the effects of CO coordination on these vibrations. The oxide-carbonyls all have a hexacoordinate core analogous to that of V(CO)6(+). The fully coordinated vanadium monoxide-carbonyl species is VO(CO)5(+), and those of the dioxide and trioxide are VO2(CO)4(+) and VO3(CO)3(+), respectively. PMID:23927497

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice.

    PubMed

    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

  10. Age-Dependent Changes in the Inflammatory Nociceptive Behavior of Mice

    PubMed Central

    King-Himmelreich, Tanya S.; Möser, Christine V.; Wolters, Miriam C.; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-01-01

    The processing of pain undergoes several changes in aging that affect sensory nociceptive fibers and the endogenous neuronal inhibitory systems. So far, it is not completely clear whether age-induced modifications are associated with an increase or decrease in pain perception. In this study, we assessed the impact of age on inflammatory nociception in mice and the role of the hormonal inhibitory systems in this context. We investigated the nociceptive behavior of 12-month-old versus 6–8-week-old mice in two behavioral models of inflammatory nociception. Levels of TRP channels, and cortisol as well as cortisol targets, were measured by qPCR, ELISA, and Western blot in the differently aged mice. We observed an age-related reduction in nociceptive behavior during inflammation as well as a higher level of cortisol in the spinal cord of aged mice compared to young mice, while TRP channels were not reduced. Among potential cortisol targets, the NF-κB inhibitor protein alpha (IκBα) was increased, which might contribute to inhibition of NF-κB and a decreased expression and activity of the inducible nitric oxide synthase (iNOS). In conclusion, our results reveal a reduced nociceptive response in aged mice, which might be at least partially mediated by an augmented inflammation-induced increase in the hormonal inhibitory system involving cortisol. PMID:26593904

  11. Age-dependent female responses to a male ejaculate signal alter demographic opportunities for selection

    PubMed Central

    Fricke, Claudia; Green, Darrell; Mills, Walter E.; Chapman, Tracey

    2013-01-01

    A central tenet of evolutionary explanations for ageing is that the strength of selection wanes with age. However, data on age-specific expression and benefits of sexually selected traits are lacking—particularly for traits subject to sexual conflict. We addressed this by using as a model the responses of Drosophila melanogaster females of different ages to receipt of sex peptide (SP), a seminal fluid protein transferred with sperm during mating. SP can mediate sexual conflict, benefitting males while causing fitness costs in females. Virgin and mated females of all ages showed significantly reduced receptivity in response to SP. However, only young virgin females also showed increased egg laying; hence, there was a narrow demographic window of maximal responses to SP. Males gained significant ‘per mating’ fitness benefits only when mating with young females. The pattern completely reversed in matings with older females, where SP transfer was costly. The overall benefits of SP transfer (hence opportunity for selection) therefore reversed with female age. The data reveal a new example of demographic variation in the strength of selection, with convergence and conflicts of interest between males and ageing females occurring over different facets of responses to a sexually antagonistic trait. PMID:23843383

  12. Age-dependent dopaminergic dysfunction following fetal exposure to atrazine in SD rats.

    PubMed

    Li, Yanshu; Sun, Yan; Yang, Junwei; Wu, Yanping; Yu, Jia; Li, Baixiang

    2014-05-01

    The herbicide, atrazine (ATR), is used worldwide and its contamination in the environment has resulted in documented human exposure. It has also been shown that ATR results in dopaminergic neurotoxicity, however, few studies have investigated the long-term effects of ATR following in utero exposure. Therefore, we evaluated the effects of ATR exposure in Sprague Dawley rats during gestational on the offspring dopaminergic system development. Pregnant dams were treated with oral ATR at 0, 25, 50 mg/kg/day from gestational day 0 to postnatal day 1. In this study, we examined the hypothesis that ATR could cross the placental barrier and have long-term adverse effects on the synthesis, degradation and reuptake of DA in the brain. For this purpose,we examine the concentration of levodopa (L-DA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in stratum. The mRNA and protein expression of orphan nuclear hormone (Nurr1), tyrosine hydroxylase(TH), vesicular monoaminetransporter 2 (VMAT2), dopamine transporter (DAT), monoamine (MAO), and catechol-O-methyl transferase (COMT) in the midbrain were examined by fluorescence PCR and Western blot when the offspring reached six-month old or one year old .When measured 6 months post-treatment, the level of DA and expression of Nurr1, VMAT2, DAT and TH were reduced in the striatum and Substantia nigra, respectively. PMID:24863964

  13. Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice.

    PubMed

    El Khoury, Noura B; Gratuze, Maud; Petry, Franck; Papon, Marie-Amélie; Julien, Carl; Marcouiller, François; Morin, Françoise; Nicholls, Samantha B; Calon, Frédéric; Hébert, Sébastien S; Marette, André; Planel, Emmanuel

    2016-04-01

    Accumulating evidence from epidemiological studies suggest that type 2 diabetes is linked to an increased risk of Alzheimer's disease (AD). However, the consequences of type 2 diabetes on AD pathologies, such as tau hyperphosphorylation, are not well understood. Here, we evaluated the impact of type 2 diabetes on tau phosphorylation in db/db diabetic mice aged 4 and 26weeks. We found increased tau phosphorylation at the CP13 epitope correlating with a deregulation of c-Jun. N-terminal kinase (JNK) and Protein Phosphatase 2A (PP2A) in 4-week-old db/db mice. 26-week-old db/db mice displayed tau hyperphosphorylation at multiple epitopes (CP13, AT8, PHF-1), but no obvious change in kinases or phosphatases, no cleavage of tau, and no deregulation of central insulin signaling pathways. In contrast to younger animals, 26-week-old db/db mice were hypothermic and restoration of normothermia rescued phosphorylation at most epitopes. Our results suggest that, at early stages of type 2 diabetes, changes in tau phosphorylation may be due to deregulation of JNK and PP2A, while at later stages hyperphosphorylation is mostly a consequence of hypothermia. These results provide a novel link between diabetes and tau pathology, and underlie the importance of recording body temperature to better understand the relationship between diabetes and AD. PMID:26777665

  14. 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.

  15. 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. PMID

  16. 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

  17. Accumulation of hyporesponsive, calcium extruding memory T cells as a key feature of age-dependent immune dysfunction.

    PubMed

    Miller, R A

    1991-03-01

    In this review I propose a hypothesis with a number of testable predictions: that the age-dependent decline in T lymphocyte function is largely the result of the accumulation of memory T lymphocytes with over-active plasma membrane calcium pumps. This idea is consistent with much, though not all, of the currently available data. I will start by presenting the evidence that suggested and most clearly supports this idea, then discuss apparently contrary data (some of it still difficult to reconcile with the model), and lastly consider the implications of the model for our understanding of late life development of the T cell immune system. PMID:2001603

  18. Age-dependent alterations in the inflammatory response to pulmonary challenge.

    PubMed

    Linge, Helena M; Ochani, Kanta; Lin, Ke; Lee, Ji Young; Miller, Edmund J

    2015-12-01

    The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 months or greater than 18 months (approximating humans of 20 and 55-65 years), were challenged, intratracheally, with lipoteichoic acid and peptidoglycan. Cellular and cytokine evaluations were performed on both bronchoalveolar lavage fluid (BAL) and plasma, 24 h post-challenge. The plasma concentration of free thyroxine, a marker of severity in non-thyroidal illness, was also evaluated. The older animals had an increased chemotactic gradient in favor of the airspaces, which was associated with a greater accumulation of neutrophils and protein. Furthermore, macrophage migration inhibitory factor (MIF), an inflammatory mediator and putative biomarker in acute lung injury, was increased in both the plasma and BAL of the older, but not young animals. Conversely, plasma free thyroxine, a natural inhibitor of MIF, was decreased in the older animals. These findings identify age-associated inflammatory/metabolic changes following pulmonary challenge that it may be possible to manipulate to improve outcome in the older, critically ill patient. PMID:26318747

  19. Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice.

    PubMed

    Müller, Sarah; Kaiser, Hannah; Krüger, Burkhard; Fitzner, Brit; Lange, Falko; Bock, Cristin N; Nizze, Horst; Ibrahim, Saleh M; Fuellen, Georg; Wolkenhauer, Olaf; Jaster, Robert

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively) triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of alpha-amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO) in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT) C57BL/6 mice were virtually indistinguishable with respect to disease severity. In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage than WT mice at late time points after the induction of AP (24 h and 7 days, respectively), suggesting retarded regeneration. Furthermore, a higher peak level of alpha-amylase activity and gradually increased MPO levels in pancreatic and lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin activities (in vivo studies) and intraacinar trypsin and elastase activation in response to cerulein treatment (in vitro studies) were not enhanced but even diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished ratio of reduced and oxidized glutathione in serum but no increased ROS levels in pancreatic acini. Together, our data indicate an aggravating effect of UCP2 deficiency on the severity of experimental AP in older but not in young mice. We suggest that increased severity of AP in 12 months old UCP2-/- is caused by an imbalanced inflammatory response but is unrelated to acinar cell functions. PMID:24721982

  20. Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice

    PubMed Central

    Krüger, Burkhard; Fitzner, Brit; Lange, Falko; Bock, Cristin N.; Nizze, Horst; Ibrahim, Saleh M.; Fuellen, Georg; Wolkenhauer, Olaf; Jaster, Robert

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively) triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of alpha-amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO) in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT) C57BL/6 mice were virtually indistinguishable with respect to disease severity. In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage than WT mice at late time points after the induction of AP (24 h and 7 days, respectively), suggesting retarded regeneration. Furthermore, a higher peak level of alpha-amylase activity and gradually increased MPO levels in pancreatic and lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin activities (in vivo studies) and intraacinar trypsin and elastase activation in response to cerulein treatment (in vitro studies) were not enhanced but even diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished ratio of reduced and oxidized glutathione in serum but no increased ROS levels in pancreatic acini. Together, our data indicate an aggravating effect of UCP2 deficiency on the severity of experimental AP in older but not in young mice. We suggest that increased severity of AP in 12 months old UCP2-/- is caused by an imbalanced inflammatory response but is unrelated to acinar cell functions. PMID:24721982

  1. Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice

    PubMed Central

    Bortolussi, Giulia; Baj, Gabriele; Vodret, Simone; Viviani, Giulia; Bittolo, Tamara; Muro, Andrés F.

    2014-01-01

    Neonatal jaundice is caused by high levels of unconjugated bilirubin. It is usually a temporary condition caused by delayed induction of UGT1A1, which conjugates bilirubin in the liver. To reduce bilirubin levels, affected babies are exposed to phototherapy (PT), which converts toxic bilirubin into water-soluble photoisomers that are readily excreted out. However, in some cases uncontrolled hyperbilirubinemia leads to neurotoxicity. To study the mechanisms of bilirubin-induced neurological damage (BIND) in vivo, we generated a mouse model lacking the Ugt1a1 protein and, consequently, mutant mice developed jaundice as early as 36 hours after birth. The mutation was transferred into two genetic backgrounds (C57BL/6 and FVB/NJ). We exposed mutant mice to PT for different periods and analyzed the resulting phenotypes from the molecular, histological and behavioral points of view. Severity of BIND was associated with genetic background, with 50% survival of C57BL/6‑Ugt1−/− mutant mice at postnatal day 5 (P5), and of FVB/NJ-Ugt1−/− mice at P11. Life-long exposure to PT prevented cerebellar architecture alterations and rescued neuronal damage in FVB/NJ-Ugt1−/− but not in C57BL/6-Ugt1−/− mice. Survival of FVB/NJ-Ugt1−/− mice was directly related to the extent of PT treatment. PT treatment of FVB/NJ-Ugt1−/− mice from P0 to P8 did not prevent bilirubin-induced reduction in dendritic arborization and spine density of Purkinje cells. Moreover, PT treatment from P8 to P20 did not rescue BIND accumulated up to P8. However, PT treatment administered in the time-window P0–P15 was sufficient to obtain full rescue of cerebellar damage and motor impairment in FVB/NJ-Ugt1−/− mice. The possibility to modulate the severity of the phenotype by PT makes FVB/NJ-Ugt1−/− mice an excellent and versatile model to study bilirubin neurotoxicity, the role of modifier genes, alternative therapies and cerebellar development during high bilirubin conditions. PMID

  2. Clinical features of schizophrenia with enhanced carbonyl stress.

    PubMed

    Miyashita, Mitsuhiro; Arai, Makoto; Kobori, Akiko; Ichikawa, Tomoe; Toriumi, Kazuya; Niizato, Kazuhiro; Oshima, Kenichi; Okazaki, Yuji; Yoshikawa, Takeo; Amano, Naoji; Miyata, Toshio; Itokawa, Masanari

    2014-09-01

    Accumulating evidence suggests that advanced glycation end products, generated as a consequence of facilitated carbonyl stress, are implicated in the development of a variety of diseases. These diseases include neurodegenerative illnesses, such as Alzheimer disease. Pyridoxamine is one of the 3 forms of vitamin B6, and it acts by combating carbonyl stress and inhibiting the formation of AGEs. Depletion of pyridoxamine due to enhanced carbonyl stress eventually leads to a decrease in the other forms of vitamin B6, namely pyridoxal and pyridoxine. We previously reported that higher levels of plasma pentosidine, a well-known biomarker for advanced glycation end products, and decreased serum pyridoxal levels were found in a subpopulation of schizophrenic patients. However, there is as yet no clinical characterization of this subset of schizophrenia. In this study, we found that these patients shared many clinical features with treatment-resistant schizophrenia. These include a higher proportion of inpatients, low educational status, longer durations of hospitalization, and higher doses of antipsychotic medication, compared with patients without carbonyl stress. Interestingly, psychopathological symptoms showed a tendency towards negative association with serum vitamin B6 levels. Our results support the idea that treatment regimes reducing carbonyl stress, such as supplementation of pyridoxamine, could provide novel therapeutic benefits for this subgroup of patients. PMID:24062594

  3. Determination of toxic carbonyl compounds in cigarette smoke.

    PubMed

    Fujioka, Kazutoshi; Shibamoto, Takayuki

    2006-02-01

    Toxic carbonyl compounds, including formaldehyde, malonaldehyde, and glyoxal, formed in mainstream cigarette smoke were quantified by derivatization-solid phase extraction-gas chromatography methods. Cigarette smoke from 14 commercial brands and one reference (2R1F) was drawn into a separatory funnel containing aqueous phosphate-buffered saline. Reactive carbonyl compounds trapped in the buffer solution were derivatized into stable nitrogen containing compounds (pyrazoles for beta-dicarbonyl and alpha,beta-unsaturated aldehyde; quinoxalines for alpha-dicarbonyls; and thiazolidines for alkanals). After derivatives were recovered using C(18) solid phase extraction cartridges, they were analyzed quantitatively by a gas chromatograph with a nitrogen phosphorus detector. The total carbonyl compounds recovered from regular size cigarettes ranged from 1.92 mg/cigarette(-1) to 3.14 mg/cigarette(-1). The total carbonyl compounds recovered from a reference cigarette and a king size cigarette were 3.23 mg/cigarette(-1) and 3.39 mg/cigarette(-1), respectively. The general decreasing order of the carbonyl compounds yielded was acetaldehyde (1110-2101 microg/cigarette(-1)) > diacetyl (301-433 microg/cigarette(-1)), acrolein (238-468 microg/cigarette(-1)) > formaldehyde (87.0-243 microg/cigarette(-1)), propanal (87.0-176 microg/cigarette(-1)) > malonaldehyde (18.9-36.0 microg/cigarette(-1)), methylglyoxal (13.4-59.6 microg/cigarette(-1)) > glyoxal (1.93-6.98 microg/cigarette(-1)). PMID:16463255

  4. 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

  5. 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

  6. Altered connexin 43 expression underlies age-dependent decrease of regulatory T cell suppressor function in nonobese diabetic mice.

    PubMed

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

    2015-06-01

    Type 1 diabetes 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. In this study, we show that regulatory T cells (T(regs)) 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 T(regs) 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 T(regs) and restore the ability of conventional CD4(+) T cells to upregulate Foxp3 and generate peripherally derived T(regs). Moreover, we demonstrate that suppression mediated by T(regs) 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 T(reg) suppression mechanism compromised in NOD mice and suggests how T(reg) mediated immune regulation can be improved. PMID:25911751

  7. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology

    PubMed Central

    Polydoro, Manuela; Acker, Christopher M.; Duff, Karen; Castillo, Pablo E.; Davies, Peter

    2009-01-01

    A hallmark feature of Alzheimer’s disease pathology is the presence of neurofibrillary tangles (NFTs), which are intracellular aggregates of conformationally abnormal and hyperphosphorylated tau. The presence of NFTs in the forebrain is associated with impairments of cognitive function, supporting a central role for tau in dementia. The significance of the accumulation of NFTs for neuronal and cognitive function is still obscure. It is possible that NFTs disrupt synaptic transmission and plasticity, leading to memory deficits and cognitive malfunction. To elucidate the relationship between the development of tau pathology and synaptic and cognitive functions, we performed behavioral tests and electrophysiological experiments in the htau mouse. Here we report age-dependent cognitive and physiological impairments in htau mice which preceded neurodegeneration. 12-month-old htau mice with moderate tau pathology, but not 4-month-old mice with early stage tau pathology, presented cognitive deficits in an object recognition memory task in which the visual recognition memory of a novel object was disrupted. Moreover, only 12-month-old htau mice exhibit spatial memory deficits, as indicated by the impaired performance in the Morris water maze. In addition, we report that basal synaptic transmission and induction of long-term potentiation with high frequency stimulation, but not theta burst stimulation, is perturbed in hippocampal CA1 region of old but not young htau mice. Our results suggest that tau pathology may underlie an age-dependent learning impairment through disruption of synaptic function. PMID:19710325

  8. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology.

    PubMed

    Polydoro, Manuela; Acker, Christopher M; Duff, Karen; Castillo, Pablo E; Davies, Peter

    2009-08-26

    A hallmark feature of Alzheimer's disease pathology is the presence of neurofibrillary tangles (NFTs), which are intracellular aggregates of conformationally abnormal and hyperphosphorylated tau. The presence of NFTs in the forebrain is associated with impairments of cognitive function, supporting a central role for tau in dementia. The significance of the accumulation of NFTs for neuronal and cognitive function is still obscure. It is possible that NFTs disrupt synaptic transmission and plasticity, leading to memory deficits and cognitive malfunction. To elucidate the relationship between the development of tau pathology and synaptic and cognitive functions, we performed behavioral tests and electrophysiological experiments in the htau mouse. Here we report age-dependent cognitive and physiological impairments in htau mice that preceded neurodegeneration. Twelve-month-old htau mice with moderate tau pathology, but not 4-month-old mice with early-stage tau pathology, presented cognitive deficits in an object recognition memory task in which the visual recognition memory of a novel object was disrupted. Moreover, only 12-month-old htau mice exhibit spatial memory deficits, as indicated by the impaired performance in the Morris water maze. In addition, we report that basal synaptic transmission and induction of long-term potentiation with high-frequency stimulation, but not theta burst stimulation, is perturbed in hippocampal CA1 region of old but not young htau mice. Our results suggest that tau pathology may underlie an age-dependent learning impairment through disruption of synaptic function. PMID:19710325

  9. Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection

    PubMed Central

    Richner, Justin M.; Gmyrek, Grzegorz B.; Govero, Jennifer; Tu, Yizheng; van der Windt, Gerritje J. W.; Metcalf, Talibah U.; Haddad, Elias K.; Textor, Johannes; Miller, Mark J.; Diamond, Michael S.

    2015-01-01

    Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection. PMID:26204259

  10. 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

  11. Age-dependent Characteristics in Women with Breast Cancer: Mastectomy and Reconstructive Trends at an Urban Academic Institution.

    PubMed

    Rodby, Katherine A; Robinson, Emilie; Danielson, Kirstie K; Quinn, Karina P; Antony, Anuja K

    2016-03-01

    Breast reconstruction is an important aspect of treatment after breast cancer. Postmastectomy reconstruction bears a significant impact on a woman's postsurgical confidence, sexuality, and overall well-being. Previous studies have inferred that women under age 40 years have unique characteristics that distinguish them from an older cohort. Identifying age-dependent trends will assist with counseling women on mastectomy and reconstruction. To identify age-dependent trends, 100 consecutive women were sampled from a prospectively maintained breast reconstruction database at an urban academic institution from June 2010 through June 2013. Women were placed into two cohorts <40 and ≥40 as well cohorts by decade (20s, 30s, 40s, 50s, and 60s). Statistical trends were reported as odds of risk per year of increasing age using logistic regression; linear regression, χ(2), and Fischer's exact were used to compare <40 and ≥40 and split cohorts for comparison. Comorbidities, tumor staging, oncologic treatment including chemotherapy and radiation, disease characteristics and genetics, and mastectomy, reconstructive and symmetry procedures were evaluated. Statistical analysis was performed using SAS software. In 100 patients of the sample study cohort, 151 reconstructions were performed. Increasing age was associated with one or more comorbidities [odds ratio (OR) = 1.07, P = 0.005], whereas younger age was associated with metastatic disease (OR = 0.88, P = 0.006), chemotherapy (OR = 0.94, P = 0.01), and radiation (OR = 0.94, P = 0.006); split cohorts demonstrated similar trends (P < 0.005). Mastectomy and reconstructive characteristics associated with younger age included bilateral mastectomy (OR = 0.94, P = 0.004), tissue expander (versus autologous flap) (OR = 0.94, P = 0.009), extra high implant type (OR = 0.94, P = 0.049), whereas increasing use of autologous flaps and contralateral mastopexy symmetry procedures (OR = 1.09, P = 0.02) were associated with an aging cohort

  12. 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.

  13. 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.

  14. Infrared Photodissociation Spectroscopy of Metal Oxide Carbonyl Cations.

    NASA Astrophysics Data System (ADS)

    Brathwaite, Antonio D.; Duncan, Michael A.

    2013-06-01

    Mass selected metal oxide-carbonyl cations of the form MO_{m}(CO)_{n}^{+} are studied via infrared laser photodissociation spectroscopy, in the 600-2300cm^{1} region. Insight into the structure and bonding of these complexes is obtained from the number of infrared active bands, their relative intensities and their frequency positions. Density functional theory calculations are carried out in support of the experimental data. Insight into the bonding of CO ligands to metal oxides is obtained and the effect of oxidation on the carbonyl stretching frequency is revealed.

  15. Strain- and Age-dependent Hippocampal Neuron Sodium Currents Correlate with Epilepsy Severity in Dravet Syndrome Mice

    PubMed Central

    Mistry, Akshitkumar M.; Thompson, Christopher H.; Miller, Alison R.; Vanoye, Carlos G.; George, Alfred L.; Kearney, Jennifer A.

    2014-01-01

    Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a knockout (Scn1a+/−) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. Scn1a+/− mice on strain 129S6/SvEvTac (129.Scn1a+/−) have no overt phenotype and normal survival compared with Scn1a+/− mice bred to C57BL/6J (F1.Scn1a+/−) that have severe epilepsy and premature lethality. We tested the hypothesis that strain differences in sodium current (INa) density in hippocampal neurons contribute to these divergent phenotypes. Whole-cell voltage-clamp recording was performed on acutely-dissociated hippocampal neurons from postnatal day 21–24 (P21–24) 129.Scn1a+/− or F1.Scn1a+/− mice and wild-type littermates. INa density was lower in GABAergic interneurons from F1.Scn1a+/− mice compared to wild-type littermates, while on the 129 strain there was no difference in GABAergic interneuron INa between 129.Scn1a+/− mice and wild-type littermate controls. By contrast, INa density was elevated in pyramidal neurons from both 129.Scn1a+/− and F1.Scn1a+/− mice, and was correlated with more frequent spontaneous action potential firing in these neurons, as well as more sustained firing in F1.Scn1a+/− neurons. We also observed age-dependent differences in pyramidal neuron INa density between wild-type and Scn1a+/− animals. We conclude that preserved INa density in GABAergic interneurons contributes to the milder phenotype of 129.Scn1a+/− mice. Furthermore, elevated INa density in excitatory pyramidal neurons at P21–24 correlates with age-dependent onset of lethality in F1.Scn1a+/− mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution of

  16. A novel NAD(P)H-dependent carbonyl reductase specifically expressed in the thyroidectomized chicken fatty liver: catalytic properties and crystal structure.

    PubMed

    Fukuda, Yudai; Sone, Takeki; Sakuraba, Haruhiko; Araki, Tomohiro; Ohshima, Toshihisa; Shibata, Takeshi; Yoneda, Kazunari

    2015-10-01

    A gene encoding a functionally unknown protein that is specifically expressed in the thyroidectomized chicken fatty liver and has a predicted amino acid sequence similar to that of NAD(P)H-dependent carbonyl reductase was overexpressed in Escherichia coli; its product was purified and characterized. The expressed enzyme was an NAD(P)H-dependent broad substrate specificity carbonyl reductase and was inhibited by arachidonic acid at 1.5 μm. Enzymological characterization indicated that the enzyme could be classified as a cytosolic-type carbonyl reductase. The enzyme's 3D structure was determined using the molecular replacement method at 1.98 Å resolution in the presence of NADPH and ethylene glycol. The asymmetric unit consisted of two subunits, and a noncrystallographic twofold axis generated the functional dimer. The structures of the subunits, A and B, differed from each other. In subunit A, the active site contained an ethylene glycol molecule absent in subunit B. Consequently, Tyr172 in subunit A rotated by 103.7° in comparison with subunit B, which leads to active site closure in subunit A. In Y172A mutant, the Km value for 9,10-phenanthrenequinone (model substrate) was 12.5 times higher than that for the wild-type enzyme, indicating that Tyr172 plays a key role in substrate binding in this carbonyl reductase. Because the Tyr172-containing active site lid structure (Ile164-Gln174) is not conserved in all known carbonyl reductases, our results provide new insights into substrate binding of carbonyl reductase. The catalytic properties and crystal structure revealed that thyroidectomized chicken fatty liver carbonyl reductase is a novel enzyme. PMID:26206323

  17. Metal telluride clusters composed of niobocene carbonyl, telluride, and cobalt carbonyl units: syntheses, structures, and reactivity

    PubMed

    Brunner; Lucas; Monzon; Mugnier; Nuber; Stubenhofer; Stuckl; Wachter; Wanninger; Zabel

    2000-02-01

    Abstract: The reaction of [Cp#2NbTe2H] (1#; Cp# = Cp* (C5Me5) or Cp(x) (C5Me4Et)) with two equivalents of [Co2(CO)8] gives a series of cobalt carbonyl telluride clusters that contain different types of niobocene carbonyl fragments. At 0 degrees C, [Cp#2NbTe2CO3(CO)7] (2#) and [Co4Te2(CO)10] (3) are formed which disappear at higher temperatures: in boiling toluene a mixture of [cat2][Co9Te6(CO)8] (5#) (cat= [Cp#2Nb(CO)2]+) and [cat2][Co11Te7(CO)10] (6#) is formed along with [cat][Co(CO)4] (4#). Complexes 6# transform into [cat][Co11Te7(CO)10] (7#) upon interaction with HPF6 or wet SiO2. The molecular structures of 2(Cp(x)), 4(Cp(x)), 5(Cp*), 6(Cp*) and 7(Cp*) have been determined by X-ray crystallography. The structure of the neutral 2(Cp(x)) consists of a [Co3(CO)6Te2] bipyramid which is connected to a [(C5Me4Et)2Nb(CO)] fragment through a mu4-Te bridge. The ionic structures of 4(Cp(x)), 5(Cp*), 6(Cp*) and 7(Cp*) each contain one (4, 7) or two (5, 6) [Cp#2Nb(CO)2]+ cations. Apart from 4, the anionic counterparts each contain an interstitial Co atom and are hexacapped cubic cluster anions [Co9Te6(CO)8]2- (5) or heptacapped pentagonal prismatic cluster anions [Co11Te7(CO)10]n- (n=2: [6]2- , n=1: [7]-), respectively. Electrochemical studies established a reversible electron transfer between the anionic clusters [Co11,Te7(CO)10]- and [Co11Te7(CO)10]2in 6# and 7# and provided evidence for the existence of species containing [Co11Te7(CO),0] and [Co11Te7(CO)0]3-. The electronic structures of the new clusters and their relative stabilities are examined by means of DFT calculations. PMID:10747416

  18. 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

  19. 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.

  20. Evidence for an Age-Dependent Decline in Axon Regeneration in the Adult Mammalian Central Nervous System.

    PubMed

    Geoffroy, Cédric G; Hilton, Brett J; Tetzlaff, Wolfram; Zheng, Binhai

    2016-04-12

    How aging impacts axon regeneration after CNS injury is not known. We assessed the impact of age on axon regeneration induced by Pten deletion in corticospinal and rubrospinal neurons, two neuronal populations with distinct innate regenerative abilities. As in young mice, Pten deletion in older mice remains effective in preventing axotomy-induced decline in neuron-intrinsic growth state, as assessed by mTOR activity, neuronal soma size, and axonal growth proximal to a spinal cord injury. However, axonal regeneration distal to injury is greatly diminished, accompanied by increased expression of astroglial and inflammatory markers at the injury site. Thus, the mammalian CNS undergoes an age-dependent decline in axon regeneration, as revealed when neuron-intrinsic growth state is elevated. These results have important implications for developing strategies to promote axonal repair after CNS injuries or diseases, which increasingly affect middle-aged to aging populations. PMID:27050519

  1. 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. PMID:19842431

  2. Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.

    PubMed

    Walter, Bernd; Brust, Peter; Füchtner, Frank; Müller, Marco; Hinz, Rainer; Kuwabara, Hiroto; Fritz, Harald; Zwiener, Ulrich; Bauer, Reinhard

    2004-08-01

    There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism. PMID:15319007

  3. 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.

  4. 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.

  5. Age-Dependent Decline in Mouse Lung Regeneration with Loss of Lung Fibroblast Clonogenicity and Increased Myofibroblastic Differentiation

    PubMed Central

    Paxson, Julia A.; Gruntman, Alisha; Parkin, Christopher D.; Mazan, Melissa R.; Davis, Airiel; Ingenito, Edward P.; Hoffman, Andrew M.

    2011-01-01

    While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration. PMID:21912590

  6. 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

  7. Age-Dependent Decrease and Alternative Splicing of Methionine Synthase mRNA in Human Cerebral Cortex and an Accelerated Decrease in Autism

    PubMed Central

    Muratore, Christina R.; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Persico, Antonio M.; Lintas, Carla; De La Monte, Suzanne; Deth, Richard C.

    2013-01-01

    The folate and vitamin B12-dependent enzyme methionine synthase (MS) is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin) from oxidation. Although three species of MS were evident at the protein level, corresponding to full-length and alternatively spliced mRNA transcripts, decreasing mRNA levels across the lifespan were not associated with significant changes in MS protein or methionine levels. MS mRNA levels were significantly lower in autistic subjects, especially at younger ages, and this decrease was replicated in cultured human neuronal cells by treatment with TNF-α, whose CSF levels are elevated in autism. These novel findings suggest that rather than serving as a housekeeping enzyme, MS has a broad and dynamic role in coordinating metabolism in the brain during development and aging. Factors adversely affecting MS activity, such as oxidative stress, can be a source of risk for neurological disorders across the lifespan via their impact on methylation reactions, including epigenetic regulation of gene expression. PMID:23437274

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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…

  13. 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...

  14. 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

  15. 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.

  16. 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

  17. Cobalt carbonyl catalyzed olefin hydroformylation in supercritical carbon dioxide

    SciTech Connect

    Rathke, J.W.; Klingler, R.J.

    1992-12-31

    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. Carbonylation Induces Heterogeneity in Cardiac Ryanodine Receptor Function in Diabetes Mellitus

    PubMed Central

    Shao, Chun Hong; Tian, Chengju; Ouyang, Shouqiang; Moore, Caronda J.; Alomar, Fadhel; Nemet, Ina; D'Souza, Alicia; Nagai, Ryoji; Kutty, Shelby; Rozanski, George J.; Ramanadham, Sasanka; Singh, Jaipaul

    2012-01-01

    Heart failure and arrhythmias occur at 3 to 5 times higher rates among individuals with diabetes mellitus, compared with age-matched, healthy individuals. Studies attribute these defects in part to alterations in the function of cardiac type 2 ryanodine receptors (RyR2s), the principal Ca2+-release channels on the internal sarcoplasmic reticulum (SR). To date, mechanisms underlying RyR2 dysregulation in diabetes remain poorly defined. A rat model of type 1 diabetes, in combination with echocardiography, in vivo and ex vivo hemodynamic studies, confocal microscopy, Western blotting, mass spectrometry, site-directed mutagenesis, and [3H]ryanodine binding, lipid bilayer, and transfection assays, was used to determine whether post-translational modification by reactive carbonyl species (RCS) represented a contributing cause. After 8 weeks of diabetes, spontaneous Ca2+ release in ventricular myocytes increased ∼5-fold. Evoked Ca2+ release from the SR was nonuniform (dyssynchronous). Total RyR2 protein levels remained unchanged, but the ability to bind the Ca2+-dependent ligand [3H]ryanodine was significantly reduced. Western blotting and mass spectrometry revealed RCS adducts on select basic residues. Mutation of residues to delineate the physiochemical impact of carbonylation yielded channels with enhanced or reduced cytoplasmic Ca2+ responsiveness. The prototype RCS methylglyoxal increased and then decreased the RyR2 open probability. Methylglyoxal also increased spontaneous Ca2+ release and induced Ca2+ waves in healthy myocytes. Treatment of diabetic rats with RCS scavengers normalized spontaneous and evoked Ca2+ release from the SR, reduced carbonylation of RyR2s, and increased binding of [3H]ryanodine to RyR2s. From these data, we conclude that post-translational modification by RCS contributes to the heterogeneity in RyR2 activity that is seen in experimental diabetes. PMID:22648972

  19. 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

  20. 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]...

  1. Experimental observation of supramolecular carbonyl-π/π-π/π-carbonyl assemblies of Cu II complex of iminodiacetate and dipyridylamine

    NASA Astrophysics Data System (ADS)

    Kumar Seth, Saikat; Dey, Biswajit; Kar, Tanusree; Mukhopadhyay, Subrata

    2010-06-01

    A mononuclear Cu II complex [Cu(IDA)(2,2'-dypam)(H 2O)]·H 2O ( 1) where H 2IDA and 2,2'-dypam are iminodiacetic acid and 2,2´-dipyridylamine, respectively, has been synthesized and characterized by X-ray single crystal structure analysis. The Cu(II) atom exhibits an unsymmetrical elongated octahedral coordination type 4 + 1 + 1. X-ray crystallography reveals that complex ( 1) has an unprecedented fac-O 2 + N(apical) IDA conformation, in the trans-site of Cu-N (IDA-like) bond, in contrast with structural co-relations for complexes with Cu/(IDA or IDA-like)/N-heterocyclic donor ratio 1/1/2 and closely related compounds fac-NO + O(apical) IDA-like conformation and one N-heterocyclic donor in the trans-site to the Cu-N (IDA-like) bond. These findings are attributed to the influence of π-π stacking, C-H⋯π interactions in the molecular recognition process. Moreover, the aromatic moieties of 2,2'-dypam are engaged in carbonyl⋯π interaction with the non-coordinated carbonyl groups of IDA ligand and giving rise to a remarkable supramolecular carbonyl-π/π-π/π-carbonyl interactions.

  2. 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

  3. Orally Administrated Lactobacillus pentosus var. plantarum C29 Ameliorates Age-Dependent Colitis by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway via the Regulation of Lipopolysaccharide Production by Gut Microbiota

    PubMed Central

    Jeong, Jin-Ju; Kim, Kyung-Ah; Jang, Se-Eun; Woo, Jae-Yeon; Han, Myung Joo; Kim, Dong-Hyun

    2015-01-01

    To evaluate the anti-inflammaging effect of lactic acid bacteria (LAB) on age-dependent inflammation, we first screened and selected a tumor necrosis factor (TNF)-α and reactive oxygen species (ROS)-inhibitory LAB, Lactobacillus pentosus var. plantarum C29, among the LABs isolated from fermented vegetables using LPS-stimulated mouse peritoneal macrophages. Oral administration of C29 (2 × 109 CFU/rat) for 8 weeks in aged Fischer 344 rats (age, 16 months) inhibited the expression of the inflammatory markers myeloperoxidase, inducible nitric oxide (NO) synthase, cyclooxygenase-2, pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP1), and mitogen-activated protein kinases (MAPKs). Treatment with C29 induced the expression of tight junction proteins ZO-1, occludin, and claudin-1, and reduced intestinal microbial LPS and plasmatic LPS levels and ROS, as well as the Firmicutes to Bacteroidetes ratio, which is significantly higher in aged rats than in young rats. C29 treatment also reduced plasmatic reactive oxygen species, malondialdehyde, C-reactive protein, and TNF-α, and suppressed expression of senescence markers p16 and p53 in the colon of the aged rats, but increased SIRT 1 expression. Based on these findings, we concluded that C29 treatment may suppress aging-dependent colitis by inhibiting NF-κB, AP1, and MAPK activation via the inhibition of gut microbiota LPS production and the induction of tight junction protein expression. PMID:25689583

  4. 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.

  5. Use of carbonyl iron to induce iron loading in the mussel Mytilus edulis

    SciTech Connect

    Bootsma, N.; Macey, D.J.; Webb, J.; Talbot, V. )

    1990-02-01

    It is now recognized that in organisms such as marine mussels, the prior presence of one metal can be important in determining the ultimate toxicological response to a second challenge by a different metal species. Thus, for example, the presence of iron in the mussel Mytilus edulis profoundly affects the subsequent accumulation of zinc. To determine these synergistic (or indeed antagonistic) effects in an organism such as the mussel, it is important to be able to both load the animal rapidly, and ensure that the metal ends up in a form which is ultimately the same as that found in the animal in the natural environment. Unfortunately, considerable problems have arisen with the form in which iron has been loaded into mussels. Recently, carbonyl iron has been used to induce iron loading in rats. This form of iron is prepared by reacting elemental iron at high temperatures with carbon monoxide to form iron pentacarbonyl. This study was thus undertaken to determine whether carbonyl iron could be used for the rapid non-toxic iron loading of the mussel Mytilus edulis. Such loading could subsequently be used for the investigation of synergistic metal accumulation in mussels, a topic of considerable interest due to their use as marine pollution indicator organisms. Biochemical aspects of this tissue iron loading, including the isolation and characterization of the major metal-binding protein ferritin, have been reported previously.

  6. 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. PMID:20298680

  7. 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

  8. Conversion coefficients for age-dependent ORNL phantoms from 137Cs in soil as a source of external exposure

    NASA Astrophysics Data System (ADS)

    Krstic, D.; Nikezic, D.

    2007-09-01

    Dose conversion coefficients for different organs of age-dependent ORNL phantoms, due to the 137Cs in soil have been calculated using the MCNP-4B code. A cylindrical source at a depth of 20 cm was subdivided into 10 smaller cylinders, each of height 2 cm. Any one of these smaller cylinders could be considered as a source of photons with the energies of 661.6 keV. The ORNL phantoms stand exactly above the center of the cylinders. MCNP-4B energy deposition tally (F6) in MeV/g per one emitted photon was used to calculate absorbed doses in organs of phantoms. Then, conversion of units was made to obtain absorbed dose in fGy (femto-Gray) per Bq s kg -1. Absorbed doses in all major organs and the remainder, defined in reports ICRP60 and 74, were calculated as a function of the 137Cs source depth. Conversion coefficients decrease as the phantom age increases.

  9. 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

  10. 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. PMID:27161522

  11. [Age-dependent changes of morphometric and histochemical characteristics of neurocytes in different ganglia of albino rats].

    PubMed

    Rumiantseva, T A

    2004-01-01

    The aim of this study was to obtain the normative data on the age-dependent transformation of morphometric and histochemical characteristics of neurocytes in different ganglia in albino rats. Cell cross-sectional area, activities of cholinesterase (demonstrated with thioacetic acid method) monoamine oxidase (demonstrated with Glenner method) were measured in neurocytes of stellate, spinal, trigeminal and gastric ganglia in rats aged 2 to 360 days. Measurements were made with the help of "Bioscan" videoanalyzer. Informational analysis was used for the evaluation of the degree of maturation of neurocyte systems. General features, age- and organ-related peculiarities of morphometric and enzyme-histochemical characteristics were established for neurocytes of different ganglia, as well as a heterochronism of their definitive state attainment. The time of stabilization for neurocytes of stellate and I thoracic spinal ganglia was the age of 60 days, for those of trigeminal ganglion and intramural gastric ganglia -90 and 120 days, respectively. By this time, neurocyte systems turned from a determined state into a probabilistic-determined one, this transformation being considered as a population stabilization. PMID:15359692

  12. Life-history differences in age-dependent expressions of multiple ornaments and behaviors in a lekking bird.

    PubMed

    Kervinen, Matti; Lebigre, Christophe; Alatalo, Rauno V; Siitari, Heli; Soulsbury, Carl D

    2015-01-01

    Age is a major factor explaining variation in life-history traits among individuals with typical patterns of increasing trait values early in life, maximum trait expression, and senescence. However, age-dependent variation in the expressions of sexually selected traits has received less attention, although such variation underpins differences in male competitive abilities and female preference, which are central to sexual selection. In contrast to previous studies focusing on single traits, we used repeated measures of seven sexually selected morphological and behavioral traits in male black grouse (Tetrao tetrix) to quantify the effects of age and life span on their expressions and quantified this variation in relation to male reproductive effort. Trait expression increased with age, but long-lived males had a slower increase and delayed maxima in trait values compared with short-lived males. There was evidence of terminal investment (increasing trait values during the last breeding season) in some traits and senescence in all traits. These trait dynamics were largely explained by the timing of male peak lekking effort. This study shows that fully understanding the variation in sexually selected traits and fitness benefits associated with sexual selection requires accounting for the complex interaction among individual age, life span, and the timing of individuals' investment in reproduction. PMID:25560550

  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. 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

  15. 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.

  16. 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.

  17. 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. PMID:26415702

  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. 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

  2. Age-dependent biochemical dysfunction in skeletal muscle of triple-transgenic mouse model of Alzheimer`s disease.

    PubMed

    Monteiro-Cardoso, Vera F; Castro, Marisa; Oliveira, M M; Moreira, Paula I; Peixoto, Francisco; Videira, Romeu A

    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

  3. Novel age-dependent learning deficits in a mouse model of Alzheimer’s disease: implications for translational research

    PubMed Central

    Montgomery, K. S.; Simmons, R. K.; Edwards, G.; Nicolle, M. M.; Gluck, M. A.; Myers, C. E.; Bizon, J. L.

    2015-01-01

    Computational modeling predicts that the hippocampus plays an important role in the ability to apply previously learned information to novel problems and situations (referred to as the ability to generalize information or simply as ‘transfer learning’). These predictions have been tested in humans using a computer-based task on which individuals with hippocampal damage are able to learn a series of complex discriminations with two stimulus features (shape and color), but are impaired in their ability to transfer this information to newly configured problems in which one of the features is altered. This deficit occurs despite the fact that the feature predictive of the reward (the relevant information) is not changed. The goal of the current study was to develop a mouse analog of transfer learning and to determine if this new task was sensitive to pathological changes in a mouse model of AD. We describe a task in which mice were able to learn a series of concurrent discriminations that contained two stimulus features (odor and digging media) and could transfer this learned information to new problems in which the irrelevant feature in each discrimination pair was altered. Moreover, we report age-dependent deficits specific to transfer learning in APP+PS1 mice relative to nontransgenic littermates. The robust impairment in transfer learning may be more sensitive to AD-like pathology than traditional cognitive assessments in that no deficits were observed in the APP+PS1 mice on the widely used Morris water maze task. These data describe a novel and sensitive paradigm to evaluate mnemonic decline in AD mouse models that has unique translational advantages over standard species-specific cognitive assessments (e.g. water maze for rodent and delayed paragraph recall for humans). PMID:19720431

  4. 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

  5. Age-Dependent Resistance to Excitotoxicity in Htt CAG140 Mice and the Effect of Strain Background

    PubMed Central

    Strong, Melissa K.; Southwell, Amber L.; Yonan, Jennifer M.; Hayden, Michael R.; MacGregor, Grant R.; Thompson, Leslie M.; Steward, Oswald

    2013-01-01

    Mouse strain background can influence vulnerability to excitotoxic neuronal cell death and potentially modulate phenotypes in transgenic mouse models of human disease. Evidence supports a contribution of excitotoxicity to the selective death of medium spiny neurons in Huntington’s disease (HD). Here, we assess whether strain differences in excitotoxic vulnerability influence striatal cell death in a knock-in mouse model of HD. Previous studies that evaluated resistance to excitotoxic lesions in several mouse models of HD had variable outcomes. In the present study, we directly compare one model on two different background strains to test the contribution of strain to excitotoxicity-mediated neurodegeneration. Mice of the FVB/N strain, which are highly vulnerable to excitotoxicity, become extremely resistant to quinolinic acid-induced striatal neurodegeneration with age, when carrying a huntingtin (Htt) allele expressing a HD transgene (CAG140). The resistance is much greater than the age-dependent resistance that has been previously reported in YAC128 mice. By 12 months of age, both heterozygous and homozygous FVB.CAG140 mice displayed virtually complete resistance to quinolinic acid-induced striatal neurodegeneration. A similar resistance develops in CAG140 mice on a C57BL/6N background although the effect size is smaller because C57BL/6N mice are already resistant due to genetic background. In a direct comparison with the YAC128 mice, FVB.CAG140 mice have greater resistance. FVB.CAG140 mice are also resistant to neurodegeneration following kainic acid-induced status epilepticus suggesting the existence of a common cellular mechanism that provides protection against multiple types of excitotoxic insult. These findings establish FVB.CAG140 mice as a useful model to investigate the cellular and molecular mechanisms that confer neuroprotection against excitotoxicity. PMID:23833693

  6. 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

  7. Age-dependent uncoupling of mitochondria from Ca2⁺ release units in skeletal muscle.

    PubMed

    Pietrangelo, Laura; D'Incecco, Alessandra; Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T; Boncompagni, Simona; Protasi, Feliciano

    2015-11-01

    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/100 µm2) and CRU-mitochondrial pair density (37.4 ± 0.8 vs. 27.0 ± 0.7 pairs/100 µm2) 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

  8. 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

  9. The number of elevated cytokines/chemokines in pre-clinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner

    PubMed Central

    Deane, Kevin D.; O’Donnell, Colin I.; Hueber, Wolfgang; Majka, Darcy S.; Lazar, Ann A.; Derber, Lezlie A.; Gilliland, William R.; Edison, Jess D.; Norris, Jill M.; Robinson, William H.; Holers, V. Michael

    2010-01-01

    Purpose Pre-clinical rheumatoid arthritis (RA) biomarker elevations were evaluated and utilized to develop a model for the prediction of time to future diagnosis of seropositive RA. Methods Stored samples from 73 military seropositive RA cases (and controls) from pre-RA diagnosis (mean 2.9 samples per case; samples collected a mean of 6.6 years prior-to-diagnosis) were tested for rheumatoid factor (RF) isotypes, anti-cyclic citrullinated peptide (anti-CCP) antibodies, 14 cytokines/chemokines (bead-based assay) and C-reactive protein (CRP). Results Pre-clinical positivity of anti-CCP and/or 2 or more RF isotypes was >96% specific for future RA. In pre-clinical RA, levels of the following were positive in a significantly greater proportion of RA cases versus controls: interleukin (IL)-1α, IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, fibroblast growth factor-2, Flt-3 ligand, tumor necrosis factor-α, interferon gamma induced protein-10, granulocyte macrophage colony-stimulating factor, and CRP. Also, increasing numbers of elevated cytokines/chemokines were present in cases nearer to the time of diagnosis. RA cases ≥40 years-old at diagnosis had a higher proportion of samples positive for cytokines/chemokines 5-10 years prior-to-diagnosis, compared to cases <40 at diagnosis (p<0.01). In regression modeling using only case samples positive for autoantibodies highly specific for future RA, increasing numbers of cytokines/chemokines predicted decreased time-to-diagnosis, and the predicted time-to-diagnosis based on cytokines/chemokines was longer in older compared to younger cases. Conclusions Autoantibodies, cytokines/chemokines and CRP are elevated in the pre-clinical period of RA development. In pre-clinical autoantibody positive cases, the number of elevated cytokines/chemokines predicts the time of diagnosis of future RA in an age-dependent manner. PMID:20597112

  10. Crystallization and preliminary X-ray diffraction analysis of (R)-carbonyl reductase from Candida parapsilosis

    PubMed Central

    Wang, Shanshan; Nie, Yao; Yan, Xu; Ko, Tzu-Ping; Huang, Chun-Hsiang; Chan, Hsiu-Chien; Guo, Rey-Ting; Xiao, Rong

    2014-01-01

    The NADH-dependent (R)-carbonyl reductase from Candida parapsilosis (RCR) catalyzes the asymmetric reduction of 2-hydroxyacetophenone (HAP) to produce (R)-1-phenyl-1,2-ethanediol [(R)-PED], which is used as a versatile building block for the synthesis of pharmaceuticals and fine chemicals. To gain insight into the catalytic mechanism, the structures of complexes of RCR with ligands, including the coenzyme, are important. Here, the recombinant RCR protein was expressed and purified in Escherichia coli and was crystallized in the presence of NAD+. The crystals, which belonged to the orthorhombic space group P212121, with unit-cell parameters a = 85.64, b = 106.11, c = 145.55 Å, were obtained by the sitting-drop vapour-diffusion method and diffracted to 2.15 Å resolution. Initial model building indicates that RCR forms a homotetramer, consistent with previous reports of medium-chain-type alcohol dehydrogenases. PMID:24915097

  11. [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

  12. 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

  13. 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 ...

  14. 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.

  15. Evidence for an age-dependent influence of environmental variations on a long-lived seabird's life-history traits.

    PubMed

    Pardo, Deborah; Barbraud, Christophe; Authier, Matthieu; Weimerskirch, Henri

    2013-01-01

    Theoretical and empirical studies have highlighted the effects of age on several life-history traits in wild populations. There is also increasing evidence for environmental effects on their demographic traits. However, quantifying how individuals differentially respond to environmental variations according to their age remains a challenge in ecology. In a population of Black-browed Albatrosses monitored during 43 years, we analyzed how life-history traits varied according to age, and whether individuals of different ages responded in different ways to environmental conditions. To do so, we: (1) examined how age affected seven life-history traits, (2) investigated differences in temporal variance of demographic traits between age classes, and (3) tested for age-dependent effects of climate and fisheries covariates on demographic traits. Overall, there was a tendency for traits to improve during the first years of life (5-10 years), to peak and remain stable at middle age (10-30 years), and decline at old ages. At young ages, survival and reproductive parameters increased, except offspring body condition at fledging, suggesting that younger parents had already acquired good foraging capacities. However, they suffered from inexperience in breeding as suggested by their higher breeding failures during incubation. There was evidence for reproductive and actuarial senescence. In particular, breeding success and offspring body condition declined abruptly, suggesting altered foraging capacities of old individuals. Middle-aged individuals had the lowest temporal variance of demographic traits. Although this is predicted by the theory of environmental canalization, it could also results from a higher susceptibility of young and old birds due to their respective inexperience and senescence. The highest temporal variances were found in old individuals. Survival was significantly influenced by sea surface temperatures in the foraging zone of this albatross population during

  16. 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

  17. Age-dependent variation in mating success of sterile male Mediterranean fruit flies (Diptera: Tephritidae): implications for sterile insect technique.

    PubMed

    Shelly, Todd E; Edu, James; Pahio, Elaine

    2007-08-01

    The sterile insect technique (SIT) is widely used in integrated programs against the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). Unfortunately, the mass-rearing procedures inherent to the SIT often lead to a reduction in the mating ability of the released males. To counter this deficiency, SIT programs rely upon the production and release of large numbers of sterile males to achieve high overflooding (sterile:wild male) ratios. To ensure a high release volume, emergence facilities release adult males at a young age (2 d old in some cases). The primary objective of this study was to describe age-dependent variation in the mating propensity and competitiveness of sterile males of C. capitata. Males that were 2 or 3 d old had lower mating propensity than males that were > or =4 d old, and 3-d-old males had lower mating competitiveness than males that were > or =4 d old. Given these results, we measured the effect of a longer holding period on male mortality in storage boxes. With delayed food placement, males held in storage boxes for 4 d after emergence showed no higher mortality than males held for only 2 d (the standard interval). Using large field enclosures, we compared the levels of egg sterility attained via releases of 2- versus 4-d-old sterile males at two overflooding ratios (5:1 and 100:1). At the lower ratio, the proportion of unhatched eggs observed for trials involving 2-d-old sterile males was not, on average, significantly higher than that observed for matings between wild flies (33 versus 25%, respectively), whereas the level of egg sterility observed for releases of 4 d old sterile males was 62%. At the 100:1 overflooding ratio, the proportion of unhatched eggs associated with the 2-d-old sterile males was 58%, a level not significantly different from that induced by 4-d-old sterile males at the 5:1 ratio and significantly lower than the level (79%) observed for 4-d-old sterile males at 100:1 overflooding ratio

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Synthesis of Diiron(I) Dithiolato Carbonyl Complexes.

    PubMed

    Li, Yulong; Rauchfuss, Thomas B

    2016-06-22

    Virtually all organosulfur compounds react with Fe(0) carbonyls to give the title complexes. These reactions are reviewed in light of major advances over the past few decades, spurred by interest in Fe2(μ-SR)2(CO)x centers at the active sites of the [FeFe]-hydrogenase enzymes. The most useful synthetic route to Fe2(μ-SR)2(CO)6 involves the reaction of thiols with Fe2(CO)9 and Fe3(CO)12. Such reactions can proceed via mono-, di-, and triiron intermediates. The reactivity of Fe(0) carbonyls toward thiols is highly chemoselective, and the resulting dithiolato complexes are fairly rugged. Thus, many complexes tolerate further synthetic elaboration directed at the organic substituents. A second major route involves alkylation of Fe2(μ-S2)(CO)6, Fe2(μ-SH)2(CO)6, and Li2Fe2(μ-S)2(CO)6. This approach is especially useful for azadithiolates Fe2[(μ-SCH2)2NR](CO)6. Elaborate complexes arise via addition of the FeSH group to electrophilic alkenes, alkynes, and carbonyls. Although the first example of Fe2(μ-SR)2(CO)6 was prepared from ferrous reagents, ferrous compounds are infrequently used, although the Fe(II)(SR)2 + Fe(0) condensation reaction is promising. Almost invariably low-yielding, the reaction of Fe3(CO)12, S8, and a variety of unsaturated substrates results in C-H activation, affording otherwise inaccessible derivatives. Thiones and related C═S-containing reagents are highly reactive toward Fe(0), often giving complexes derived from substituted methanedithiolates and C-H activation. PMID:27258046

  3. 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...

  4. 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.

  5. Vasoactive Intestinal Peptide Knockout (VIP KO) mouse model of sulfite-sensitive asthma: up-regulation of novel lung carbonyl reductase

    PubMed Central

    2011-01-01

    Background We earlier reported spontaneous features of asthma in Vasoactive Intestinal Peptide knockout mice (VIP KO): 1) peribronchiolar airway inflammation, with accumulation of lymphocytes and eosinophils, 2) pro-inflammatory cytokine production of IL-5, IL-6, with IFN-γ, and 3) airway hyper-responsiveness to inhaled methacholine. In human asthma, a phenotype with sulfite sensitivity leads to airway inflammation and hyper-responsiveness to inhaled sulfites, and is associated with upregulation of anti-oxidant protein lung carbonyl reductase. For the present experiments, we examined the role of VIP in modulating anti-oxidant genes and their proteins, including lung carbonyl reductase. Results Four male VIP KO mice and four wild-type age- and gender matched mice had lungs examined for whole genome microarray and a proteomics approach using mass spectrometry. The proteomics analysis revealed that a novel variant of anti-oxidant protein lung carbonyl reductase (car3) was uniquely and markedly elevated in the VIP KO mice. RT-PCR indicated that carbonic anhydrase 3, which is an anti-oxidant protein, was elevated in the VIP KO mice. Conclusions These data support the concept that VIP influences the endogenous oxidant/antioxidant balance. One potential implication is that VIP and its analogues may be used to treat inflammatory diseases, including asthma. PMID:22103391

  6. 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

  7. 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.

  8. 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

  9. The carbonyl oxide-aldehyde complex: a new intermediate of the ozonolysis reaction

    NASA Astrophysics Data System (ADS)

    Cremer, Dieter; Kraka, Elfi; McKee, M. L.; Radharkrishnan, T. P.

    1991-12-01

    MP4(SDQ)/6-31G (d,p) calculations suggest that the ozonolysis of alkenes in solution phase does not proceed via carbonyl oxide, but via a dipole complex between aldehyde and carbonyl oxide, which is 9 kcal/mol more stable than the separated molecules. The dipole complex is probably formed in the solvent cage upon decomposition of primary ozonide to aldehyde and carbonyl oxide. Rotation of either aldehyde or carbonyl oxide in the solvent cage leads to an antiparallel alignment of molecular dipole moments and dipole-dipole attraction.

  10. 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.

  11. Indoor and outdoor carbonyl compounds in the hotel ballrooms in Guangzhou, China

    NASA Astrophysics Data System (ADS)

    Feng, Yanli; Wen, Sheng; Wang, Xinming; Sheng, Guoying; He, Qiusheng; Tang, Jianhui; Fu, Jiamo

    Twenty-one carbonyl compounds were measured simultaneously at four hotel ballrooms in urban Guangzhou during the autumn, 2002. In each ballroom, measurements were carried out in business hours in the evening (20:30-24:00) on 7 consecutive days without any disturbance of the ballroom's normal operation. Nineteen out of the 21 target carbonyl compounds were identified in indoor and outdoor air. In the outdoor environment, formaldehyde was the most abundant carbonyl, followed by acetaldehyde, and there existed a strong correlation between formaldehyde and acetaldehyde. In the indoor air, however, acetaldehyde was the most abundant carbonyl, its concentrations seemed to be affected significantly by smoking. The indoor concentrations of carbonyls were found higher than their outdoor counterparts with only a few exceptions. Further studies concerning the indoor/outdoor ratios and mutual correlation of the carbonyls indicated that apart from direct emission from indoor materials and infiltration of outdoor air, other anthropogenic sources, e.g. tobacco smoke, also significantly contributed to carbonyl compounds. The possible sources of some high molecular weight carbonyls, e.g. nonanaldehyde, were also discussed briefly. Preliminary estimate of the exposures and risks due to carbonyls in the ballrooms was made, which indicated that long-term exposure in such places might cause increased chance of developing cancers.

  12. Age-Dependent Changes in the Proteome Following Complete Spinal Cord Transection in a Postnatal South American Opossum (Monodelphis domestica)

    PubMed Central

    Noor, Natassya M.; Steer, David L.; Wheaton, Benjamin J.; Ek, C. Joakim; Truettner, Jessie S.; Dietrich, W. Dalton; Dziegielewska, Katarzyna M.; Richardson, Samantha J.; Smith, A. Ian; VandeBerg, John L.; Saunders, Norman R.

    2011-01-01

    Recovery from severe spinal injury in adults is limited, compared to immature animals who demonstrate some capacity for repair. Using laboratory opossums (Monodelphis domestica), the aim was to compare proteomic responses to injury at two ages: one when there is axonal growth across the lesion and substantial behavioural recovery and one when no axonal growth occurs. Anaesthetized pups at postnatal day (P) 7 or P28 were subjected to complete transection of the spinal cord at thoracic level T10. Cords were collected 1 or 7 days after injury and from age-matched controls. Proteins were separated based on isoelectric point and subunit molecular weight; those whose expression levels changed following injury were identified by densitometry and analysed by mass spectrometry. Fifty-six unique proteins were identified as differentially regulated in response to spinal transection at both ages combined. More than 50% were cytoplasmic and 70% belonged to families of proteins with characteristic binding properties. Proteins were assigned to groups by biological function including regulation (40%), metabolism (26%), inflammation (19%) and structure (15%). More changes were detected at one than seven days after injury at both ages. Seven identified proteins: 14-3-3 epsilon, 14-3-3 gamma, cofilin, alpha enolase, heart fatty acid binding protein (FABP3), brain fatty acid binding protein (FABP7) and ubiquitin demonstrated age-related differential expression and were analysed by qRT-PCR. Changes in mRNA levels for FABP3 at P7+1day and ubiquitin at P28+1day were statistically significant. Immunocytochemical staining showed differences in ubiquitin localization in younger compared to older cords and an increase in oligodendrocyte and neuroglia immunostaining following injury at P28. Western blot analysis supported proteomic results for ubiquitin and 14-3-3 proteins. Data obtained at the two ages demonstrated changes in response to injury, compared to controls, that were different for

  13. 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

  14. 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

  15. Carbonyl reductase of dog liver: purification, properties, and kinetic mechanism.

    PubMed

    Hara, A; Nakayama, T; Deyashiki, Y; Kariya, K; Sawada, H

    1986-01-01

    A carbonyl reductase has been extracted into 0.5 M KCl from dog liver and purified to apparent homogeneity by a three-step procedure consisting of chromatography on CM-Sephadex, Matrex green A, and Sephadex G-100 in high-ionic-strength buffers. The enzyme is a dimer composed of two identical subunits of molecular weight 27,000. The pH optimum is 5.5 and the isoelectric point of the enzyme is 9.3. The enzyme reduces aromatic ketones and aldehydes; the aromatic ketones with adjacent medium alkyl chains are the best substrates. Quinones, ketosteroids, prostaglandins, and aliphatic carbonyl compounds are poor or inactive substrates for the enzyme. As a cofactor the enzyme utilizes NADPH, the pro-S hydrogen atom of which is transferred to the substrate. Two moles of NADPH bind to one mole of the enzyme molecule, causing a blue shift and enhancement of the cofactor fluorescence. The reductase reaction is reversible and the equilibrium constant determined at pH 7.0 is 12.8. Steady-state kinetic measurements in both directions suggest that the reaction proceeds through a di-iso ordered bi-bi mechanism. PMID:3511844

  16. Prosthetic iodination methods for radiolabeling of carbonyl moieties

    SciTech Connect

    Barakat, B.M.A.

    1987-01-01

    The demonstrable need for an indirect, prosthetic-group, radioiodination of carbonyl-containing biomolecules such as ketosteroids, carbohydrates, gangliosides, glycoproteins and aldehydo- and keto-drugs. This need has been addressed by developing a route to iodinated (radioiodination) aryl hydrazides which are subsequently condensed with carbonyl-containing moieties. This dissertation is directed at improving the utility of this reaction and at comparing the hydrolytic stability of the resulting hydrazones to that of similar tyramine imines, a type presently employed in indirect radioiodinations. The aryl carboxylic acid hydrazones were virtually inert to hydrolysis under simulated physiological conditions which caused imine bond rupture. Further improvements to this new prosthetic labeling method were sought in simplifying its two-step, acid-catalyzed cleavage of triazenooxadiazoles (the protected, pre-labeling form of the aryl carboxylic acid hydrazides) to the iodinated hydrazide. Synthetic procedures were explored which might yield non-conjugated aryl oxadiazoles--bearing methylenes inserted between the phenyl and the heterocyclic ring--in the expectation that these substances would be less stable and would hydrolyze in a single-acid-catalyzed step. Four synthetic pathways to amino (or nitro) aryl-methyl oxadiazoles could not be advanced beyond the open-chain precursors of the heterocyclics. Pyrolysis, thermolysis, and catalyzed cyclization reagents could not effect ring closure. A method was developed, however, to an oxadiazolone which can serve as a protective functionality for the iodinated aryl acid hydrazides.

  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. What about the future of carbonylation reactions? CO is already one of the most versatile C1 building blocks for organic synthesis and is widely used in industry. However, because of CO's high toxicity and gaseous nature, organic chemists are often reluctant to apply carbonylations more frequently. In addition, new regulations have recently made the transportation of carbon monoxide more difficult. Hence, researchers will need to develop and more frequently use practical and benign CO-generating reagents. Apart from formates, alcohols, and metal

  18. Carbonylation reactions of alkyl iodides through the interplay of carbon radicals and Pd catalysts.

    PubMed

    Sumino, Shuhei; Fusano, Akira; Fukuyama, Takahide; Ryu, Ilhyong

    2014-05-20

    Numerous methods for transition metal catalyzed carbonylation reactions have been established. Examples that start from aryl, vinyl, allyl, and benzyl halides to give the corresponding carboxylic acid derivatives have all been well documented. In contrast, the corresponding alkyl halides often encounter difficulty. This is inherent to the relatively slow oxidative addition step onto the metal center and subsequent β-hydride elimination which causes isomerization of the alkyl metal species. Radical carbonylation reactions can override such problems of reactivity; however, carbonylation coupled to iodine atom transfer (atom transfer carbonylation), though useful, often suffers from a slow iodine atom transfer step that affects the outcome of the reaction. We found that atom transfer carbonylation of primary, secondary, and tertiary alkyl iodides was efficiently accelerated by the addition of a palladium catalyst under light irradiation. Stereochemical studies support a mechanistic pathway based on the synergic interplay of radical and Pd-catalyzed reaction steps which ultimately lead to an acylpalladium species. The radical/Pd-combined reaction system has a wide range of applications, including the synthesis of carboxylic acid esters, lactones, amides, lactams, and unsymmetrical ketones such as alkyl alkynyl and alkyl aryl ketones. The design of unique multicomponent carbonylation reactions involving vicinal C-functionalization of alkenes, double and triple carbonylation reactions, in tandem with radical cyclization reactions, has also been achieved. Thus, the radical/Pd-combined strategy provides a solution to a longstanding problem of reactivity involving the carbonylation of alkyl halides. This novel methodology expands the breadth and utility of carbonylation chemistry over either the original radical carbonylation reactions or metal-catalyzed carbonylation reactions. PMID:24712759

  19. Involvement of Prx3, a Drosophila ortholog of the thiol-dependent peroxidase PRDX3, in age-dependent oxidative stress resistance.

    PubMed

    Kayashima, Yasunari; Yamakawa-Kobayashi, Kimiko

    2012-01-01

    Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thioredoxin-dependent peroxidases. We used Drosophila melanogaster to examine the function of Prx3, the Drosophila homolog of human PRDX3. The oxidative stress response in adult Drosophila is age-dependent. RNAiinduced Prx3 knockdown in adult flies did not change their phenotype in normal conditions, but they had a shorter survival than the Prx3(+) controls in the presence of H2O2. The expression levels of the Prx3 were reduced by aging. These results suggest that Prx3 plays an important role in the oxidative stress response and is involved in the age-dependent competence of the oxidative stress response. PMID:23124252

  20. Melatonin membrane receptor (MT1R) expression and nitro-oxidative stress in testis of golden hamster, Mesocricetus auratus: An age-dependent study.

    PubMed

    Mukherjee, Arun; Haldar, Chandana

    2015-09-01

    Age-dependent decline in melatonin level induces nitro-oxidative stress that compromises physiological homeostasis including reproduction. However, less information exist regarding the age-dependent variation in local melatonin (lMel) concentration and MT1R expression in testis and its interaction with testicular steroidogenesis and nitro-oxidative stress in golden hamster, Mesocricetus auratus. Therefore, we evaluated lMel level along with MT1R expression and its possible interaction with steroidogenesis and nitro-oxidative stress in testes of young (6weeks), adult (15weeks) and old (2years) aged hamsters. Further, we injected the old hamsters with melatonin to address whether age-related decline in lMel and MT1R is responsible for the reduction in testicular steroidogenesis and antioxidant status. Increased expression of steroidogenic markers suggests increased testicular steroidogenesis in adult hamsters that declined in old hamsters. An age-dependent elevation in the level of NOX, TBARS, corticosterone and the expression of iNOS and GR with a concomitant decrease in enzyme activities for SOD, CAT, GSH-PX indicate increased nitro-oxidative stress in testes. Data suggest that reproductive senescence in male hamsters might be a consequence of declined lMel concentration with MT1R expression inducing nitro-oxidative stress resulting in diminished testicular steroidogenesis. However, administration of Mel in old-aged hamsters significantly increased steroidogenesis and antioxidant status without a significant variation in lMel concentration and MT1R expression in testes. Therefore, decreased lMel and MT1R might not be the causative factor underlying the age-associated decrease in antioxidant defence and steroidogenesis in testes. In conclusion, Mel induced amelioration of testicular oxidative insult and elevation of steroidogenic activity suggests a potential role of increased nitro-oxidative stress underlying the age-dependent decrease in steroidogenesis. PMID

  1. Vaccination against rubella: Analysis of the temporal evolution of the age-dependent force of infection and the effects of different contact patterns

    NASA Astrophysics Data System (ADS)

    Amaku, M.; Coutinho, F. A.; Azevedo, R. S.; Burattini, M. N.; Lopez, L. F.; Massad, E.

    2003-05-01

    In this paper, we analyze the temporal evolution of the age-dependent force of infection and incidence of rubella, after the introduction of a very specific vaccination program in a previously nonvaccinated population where rubella was in endemic steady state. We deduce an integral equation for the age-dependent force of infection, which depends on a number of parameters that can be estimated from the force of infection in a steady state prior to the vaccination program. We present the results of our simulations, which are compared with observed data. We also examine the influence of contact patterns among members of a community on the age-dependent intensity of transmission of rubella and on the results of vaccination strategies. As an example of the theory proposed, we calculate the effects of vaccination strategies for four communities from Caieiras (Brazil), Huixquilucan (Mexico), Finland, and the United Kingdom. The results for each community differ considerably according to the distinct intensity and pattern of transmission in the absence of vaccination. We conclude that this simple vaccination program is not very efficient (very slow) in the goal of eradicating the disease. This gives support to a mixed strategy, proposed by Massad et al., accepted and implemented by the government of the State of São Paulo, Brazil.

  2. The ability of lens alpha crystallin to protect against heat-induced aggregation is age-dependent

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    Alpha crystallin was prepared from newborn and aged bovine lenses. SDS-PAGE and tryptic peptide mapping demonstrated that both preparations contained only the alpha-A and alpha-B chains, with no significant contamination of other crystallins. Compared with alpha crystallin from the aged lens, alpha crystallin from the newborn lens was much more effective in the inhibition of beta L crystallin denaturation and precipitation induced in vitro by heat. Together, these results demonstrate that during the aging process, the alpha crystallins lose their ability to protect against protein denaturation, consistent with the hypothesis that the alpha crystallins play an important role in the maintenance of protein native structure in the intact lens.

  3. Ketene as a Reaction Intermediate in the Carbonylation of Dimethyl Ether to Methyl Acetate over Mordenite.

    PubMed

    Rasmussen, Dominik B; Christensen, Jakob M; Temel, Burcin; Studt, Felix; Moses, Poul Georg; Rossmeisl, Jan; Riisager, Anders; Jensen, Anker D

    2015-06-15

    Unprecedented insight into the carbonylation of dimethyl ether over Mordenite is provided through the identification of ketene (CH2CO) as a reaction intermediate. The formation of ketene is predicted by detailed DFT calculations and verified experimentally by the observation of doubly deuterated acetic acid (CH2DCOOD), when D2O is introduced in the feed during the carbonylation reaction. PMID:25967363

  4. 40 CFR 721.10705 - Aromatic amine with cyclo amino carbonyls (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Aromatic amine with cyclo amino... Specific Chemical Substances § 721.10705 Aromatic amine with cyclo amino carbonyls (generic). (a) Chemical... as aromatic amine with cyclo amino carbonyls (PMN P-12-572) is subject to reporting under...

  5. In Situ Derivatization and Quantification of Seven Carbonyls in Cigarette Mainstream Smoke.

    PubMed

    Ding, Yan S; Yan, Xizheng; Wong, Joshua; Chan, Michele; Watson, Clifford H

    2016-01-19

    Carbonyls, especially aldehydes, are a group of harmful volatile organic compounds that are found in tobacco smoke. Seven carbonyls are listed on the FDA's harmful and potential harmful constituents list for tobacco or tobacco smoke. Carbonyls have reactive functional groups and thus are challenging to quantitatively measure in cigarette smoke. The traditional method of measuring carbonyls in smoke involves solvent-filled impinger trapping and derivatization. This procedure is labor-intensive and generates significant volumes of hazardous waste. We have developed a new method to efficiently derivatize and trap carbonyls from mainstream smoke in situ on Cambridge filter pads. The derivatized carbonyls are extracted from the pads and subsequently quantified by ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry. The new method has been validated and applied to research and commercial cigarettes. Carbonyl yields from research cigarettes are comparable to those from other published literature data. With a convenient smoke collection apparatus, a 4 min sample analysis time, and a low- or submicrogram detection limit, this new method not only simplifies and speeds the detection of an important class of chemical constituents in mainstream smoke but also reduces reactive losses and provides a more accurate assessment of carbonyl levels in smoke. Excellent accuracy (average 98%) and precision (14% average relative standard deviation in research cigarettes) ensure this new method's sufficient fidelity to characterize conventional combusted tobacco products, with potential application toward new or emerging products. PMID:26700249

  6. Metal-atom fluorescence from the quenching of metastable rare gases by metal carbonyls

    SciTech Connect

    Hollingsworth, W.E.

    1982-11-01

    A flowing afterglow apparatus was used to study the metal fluorescence resulting from the quenching of metastable rare-gas states by metal carbonyls. The data from the quenching or argon, neon, and helium by iron and nickel carbonyl agreed well with a restricted degree of freedom model indicating a concerted bond-breaking dissociation.

  7. PROCESS OF COATING WITH NICKEL BY THE DECOMPOSITION OF NICKEL CARBONYL

    DOEpatents

    Hoover, T.B.

    1959-04-01

    An improved process is presented for the deposition of nickel coatings by the thermal decomposition of nickel carbonyl vapor. The improvement consists in incorporating a small amount of hydrogen sulfide gas in the nickel carbonyl plating gas. It is postulated that the hydrogen sulfide functions as a catalyst. i

  8. Versatile, mild, and selective reduction of various carbonyl groups using an electron-deficient boron catalyst.

    PubMed

    Lucas, Katherine M; Kleman, Adam F; Sadergaski, Luke R; Jolly, Caitlyn L; Bollinger, Brady S; Mackesey, Brittany L; McGrath, Nicholas A

    2016-06-15

    A mild and selective new method was discovered to reduce acetanilides and other carbonyl compounds. Unlike sodium borohydride, which is selective in reducing aldehydes and ketones, this new protocol is uniquely selective in reducing acetanilides and nitriles over other carbonyl containing functional groups. Additionally, β-ketoamides were shown to be reduced at the ketone preferentially over the amide. PMID:27005847

  9. Impact of HVAC filter on indoor air quality in terms of ozone removal and carbonyls generation

    NASA Astrophysics Data System (ADS)

    Lin, Chi-Chi; Chen, Hsuan-Yu

    2014-06-01

    This study aims at detecting ozone removal rates and corresponding carbonyls generated by ozone reaction with HVAC filters from various building, i.e., shopping mall, school, and office building. Studies were conducted in a small-scale environmental chamber. By examining dust properties including organic carbon proportion and specific surface area of dusts adsorbed on filters along with ozone removal rates and carbonyls generation rate, the relationship among dust properties, ozone removal rates, and carbonyls generation was identified. The results indicate a well-defined positive correlation between ozone removal efficiency and carbonyls generation on filters, as well as a positive correlation among the mass of organic carbon on filters, ozone removal efficiency and carbonyls generations.

  10. Zirconocene-Mediated Carbonylative Coupling of Grignard Reagents.

    PubMed

    Moss, Melissa; Han, Xinping; Ready, Joseph M

    2016-08-16

    Organozirconocenes are versatile synthetic intermediates that can undergo carbonylation to yield acyl anion equivalents. Zirconocene hydrochloride ([Cp2 ZrHCl]) is often the reagent of choice for accessing these intermediates but generates organozirconocenes only from alkenes and alkynes. This requirement eliminates a broad range of substrates. For example, organozirconocenes in which the zirconium center is bonded to an aromatic ring, a benzylic group, or an alkyl group that possesses a tertiary or quaternary carbon atom α to the carbon-zirconium bond can not be formed in this way. To provide more generalized access to acyl zirconium reagents, we explored the transmetalation of Grignard reagents with zirconocene dichloride under a CO atmosphere. This protocol generates acyl zirconium(IV) complexes that are inaccessible with the Schwartz reagent, including those derived from secondary and tertiary alkyl and aryl Grignard reagents. PMID:27410720

  11. Photosynthetic Control of Atmospheric Carbonyl Sulfide during the Growing Season

    NASA Technical Reports Server (NTRS)

    Campbell, J. Elliott; Carmichael, Gregory R.; Chai, T.; Mena-Carrasco, M.; Tang, Y.; Blake, D. R.; Blake, N. J.; Vay, Stephanie A.; Collatz, G. James; Baker, I.; Berry, J. A.; Montzka, S. A.; Sweeney, C.; Schnoor, J. L.; Stanier, Charles O.

    2008-01-01

    Climate models incorporate photosynthesis-climate feedbacks, yet we lack robust tools for large-scale assessments of these processes. Recent work suggests that carbonyl sulfide (COS), a trace gas consumed by plants, could provide a valuable constraint on photosynthesis. Here we analyze airborne observations of COS and carbon dioxide concentrations during the growing season over North America with a three-dimensional atmospheric transport model. We successfully modeled the persistent vertical drawdown of atmospheric COS using the quantitative relation between COS and photosynthesis that has been measured in plant chamber experiments. Furthermore, this drawdown is driven by plant uptake rather than other continental and oceanic fluxes in the model. These results provide quantitative evidence that COS gradients in the continental growing season may have broad use as a measurement-based photosynthesis tracer.

  12. Magnetorheological Characterization of Organoclay Added Carbonyl-Iron Suspensions

    NASA Astrophysics Data System (ADS)

    Lim, S. T.; Cho, M. S.; Choi, H. J.; Jhon, M. S.

    Carbonyl-iron (CI) based magnetorheological (MR) fluid containing submicron-sized additive particles was prepared. The flow behavior at steady and oscillatory shear modes was investigated by comparing flow properties of CI-mineral oil suspensions without an additive via precise control of magnetic field strength. To enhance the dispersion stability and to examine submicron-sized filler effect for the CI suspensions, organically modified montmorillonite (organoclay) was added to the CI suspensions. In addition, with the precision control of magnetic field strength, we examined the novel features of submicron-sized particle filled CI suspensions, especially under weak magnetic field strengths, in steady shear modes; a temporal decrease of steady shear viscosity in sweeping magnetic field strengths was observed.

  13. Pt and Pt/(Cu) Carbonyl clusters synthesized by radiolysis

    NASA Astrophysics Data System (ADS)

    Le Gratiet, B.; Remita, H.; Picq, G.; Delcourt, M. O.

    1996-02-01

    In the mixed solvent: 50/50% v/v water/2-propanol, [Pt 3(CO) 6] n2- clusters with n = 3-10 have been obtained by irradiating solutions containing K 2PtCl 4 under 1 atm CO. n is deduced from the very typical UV-visible and IR absorption spectra. The reduction occurs by a combined effect of CO and of the radicals produced by radiolysis (radiocatalysis). The synthesis is selective: the nuclearity n can be chosen by adjusting the dose (high doses yield low n values). Increasing the Pt salt concentration leads to CO-stabilized subcolloid particles. Intermetallic cluster compounds are expected from solutions containing two metal salts: bimetallic Pt/Cu carbonyl clusters have been obtained. Two distinct compounds have been characterized by their UV-visible spectra. Attempts with Pt/Ru and Pt/Sn systems were unsuccessful.

  14. Gas-phase reactivity of ruthenium carbonyl cluster anions.

    PubMed

    Henderson, Matthew A; Kwok, Samantha; McIndoe, J Scott

    2009-04-01

    Partially-ligated anionic ruthenium carbonyl clusters react with alkenes, arenes, and alkanes in the gas phase; the products undergo extensive C-H activation and lose dihydrogen and carbon monoxide under collision-induced dissociation conditions. Triethylsilane and phenylsilane are also reactive towards the unsaturated clusters, and oxygen was shown to rapidly break down the cluster core by oxidative cleavage of the metal-metal bonds. These qualitative gas-phase reactivity studies were conducted using an easily-installed and inexpensive modification of a commercial electrospray ionization mass spectrometer. Interpretation of the large amounts of data generated in these studies is made relatively straightforward by employing energy-dependent electrospray ionization mass spectrometry (EDESI-MS). PMID:19185511

  15. Synthesis, characterization and bioactivities of N,O-carbonylated chitosan.

    PubMed

    Liu, Hongli; Liu, Xiaoli; Yue, Lin; Jiang, Qixing; Xia, Wenshui

    2016-10-01

    N,O-Carbonylated chitosan derivative (NTCS) was synthesized via oxidation and substitution reaction, respectively. The carboxyethylation of the polysaccharide was identified by Fourier transform infrared (FTIR), (1)H nuclear magnetic resonance (NMR), X-ray diffraction analysis (XRD), Zeta potential measurement and Thermogravimetric analysis (TGA). It is revealed that compared with chitosan (CS), NTCS exhibited an excellent solubility in distilled water, high in vitro bile acid binding capacity, as well as a low viscosity. The in vitro bile acid binding capacity reached 17.21mg/g, which was 4.5-fold higher than that of CS. The results suggest that NTCS may be useful as a potential functional food supplement in food industry or a key ingredient in the pharmaceutical industry. These findings provide important supports for developing new food additive, and expand the scope of application of CS in the food industry. PMID:27189702

  16. Age-dependent roles of peroxisomes in the hippocampus of a transgenic mouse model of Alzheimer’s disease

    PubMed Central

    2013-01-01

    Background Alzheimer’s Disease (AD) is a progressive neurodegenerative disease, especially affecting the hippocampus. Impairment of cognitive and memory functions is associated with amyloid β-peptide-induced oxidative stress and alterations in lipid metabolism. In this scenario, the dual role of peroxisomes in producing and removing ROS, and their function in fatty acids β-oxidation, may be critical. This work aims to investigating the possible involvement of peroxisomes in AD onset and progression, as studied in a transgenic mouse model, harboring the human Swedish familial AD mutation. We therefore characterized the peroxisomal population in the hippocampus, focusing on early, advanced, and late stages of the disease (3, 6, 9, 12, 18 months of age). Several peroxisome-related markers in transgenic and wild-type hippocampal formation were comparatively studied, by a combined molecular/immunohistochemical/ultrastructural approach. Results Our results demonstrate early and significant peroxisomal modifications in AD mice, compared to wild-type. Indeed, the peroxisomal membrane protein of 70 kDa and acyl-CoA oxidase 1 are induced at 3 months, possibly reflecting the need for efficient fatty acid β-oxidation, as a compensatory response to mitochondrial dysfunction. The concomitant presence of oxidative damage markers and the altered expression of antioxidant enzymes argue for early oxidative stress in AD. During physiological and pathological brain aging, important changes in the expression of peroxisome-related proteins, also correlating with ongoing gliosis, occur in the hippocampus. These age- and genotype-based alterations, strongly dependent on the specific marker considered, indicate metabolic and/or numerical remodeling of peroxisomal population. Conclusions Overall, our data support functional and biogenetic relationships linking peroxisomes to mitochondria and suggest peroxisomal proteins as biomarkers/therapeutic targets in pre-symptomatic AD. PMID

  17. An oxidoreductase from 'Alphonso' mango catalyzing biosynthesis of furaneol and reduction of reactive carbonyls.

    PubMed

    Kulkarni, Ram; Chidley, Hemangi; Deshpande, Ashish; Schmidt, Axel; Pujari, Keshav; Giri, Ashok; Gershenzon, Jonathan; Gupta, Vidya

    2013-01-01

    Two furanones, furaneol (4-hydroxy-2,5-dimethyl-3(2H)-furanone) and mesifuran (2,5-dimethyl-4-methoxy-3(2H)-furanone), are important constituents of flavor of the Alphonso cultivar of mango (Mangifera indica). To get insights into the biosynthesis of these furanones, we isolated an enone oxidoreductase gene from the Alphonso mango. It has high sequence similarity to an alkenal/one oxidoreductase from cucumber (79% identity) and enone oxidoreductases from tomato (73% identity) and strawberry (72% identity). The complete open reading frame was expressed in E. coli and the (his)6-tagged recombinant protein was purified by affinity chromatography. The purified protein assayed with NADH as a reducing agent converted D-fructose-1,6-diphosphate into furaneol, the immediate precursor of mesifuran. The enzyme was also able to convert two highly reactive carbonyls, 3-buten-2-one and 1-penten-3-one, produced by lipid peroxidation in plants, into their saturated derivatives. Expression profiling in various ripening stages of Alphonso fruits depicted an expression maxima at 10 days after harvest stage, shortly before the appearance of the maximum amount of furanones (completely ripe stage, 15 days after harvest). Although no furanones were detected at the 0 day after harvest stage, significant expression of this gene was detected in the fruits at this stage. Overall, the results suggest that this oxidoreductase plays important roles in Alphonso mango fruits. PMID:24133645

  18. Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic neuron degeneration and neuroinflammation is age-dependent.

    PubMed

    Frau, Lucia; Costa, Giulia; Porceddu, Pier Francesca; Khairnar, Amit; Castelli, Maria Paola; Ennas, Maria Grazia; Madeddu, Camilla; Wardas, Jadwiga; Morelli, Micaela

    2016-01-01

    Previous studies have demonstrated that caffeine administration to adult mice potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). As neuroinflammatory response seems to correlate with neurodegeneration, and the young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine neuron degeneration and glial activation in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were treated with MDMA (4 × 20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, neuronal nitric oxide synthase (nNOS) were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary acidic protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers in CPu were only decreased in adults. In CPu of adolescent mice, caffeine potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b, whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS, IL-1β, and TNF-α were increased by MDMA in CPu of adults, whereas in adolescents, levels were only elevated after combined MDMA plus caffeine. Caffeine alone modified only nNOS. Results suggest that the use of MDMA in association with caffeine during adolescence may exacerbate the neurotoxicity and neuroinflammation elicited by MDMA. Previous studies have demonstrated that caffeine potentiated glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA) in adult mice. In this study, caffeine was shown to potentiate MDMA-induced dopamine neuron degeneration in substantia nigra pars compacta, astrogliosis, and TNF-α levels in caudate-putamen of adolescent mice. Results suggest that combined use of MDMA plus caffeine during adolescence may worsen the neurotoxicity and neuroinflammation elicited by MDMA. PMID:26442661

  19. Palladium-Catalyzed Carbonylative Cyclization of Arenes by C-H Bond Activation with DMF as the Carbonyl Source.

    PubMed

    Chen, Jianbin; Feng, Jian-Bo; Natte, Kishore; Wu, Xiao-Feng

    2015-11-01

    A novel palladium-catalyzed CO-gas- and autoclave-free protocol for the synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones has been developed. Quinazolinones, which are omnipresent motif in many pharmaceuticals and agrochemicals, were prepared in good yields by C-H bond activation and annulation using DMF as the CO surrogate. A (13) CO-labelled DMF control experiment demonstrated that CO gas was released from the carbonyl of DMF with acid as the promotor. The kinetic isotope effect (KIE) value indicated that the C-H activation step may not be involved in the rate-determining step. This methodology is operationally simple and showed a broad substrate scope with good to excellent yields. PMID:26406903

  20. [Source emission characteristics of malodorous volatile organic carbonyls from a municipal sewage treatment plant].

    PubMed

    Zhou, Mi; Wang, Bo-Guang; Zhao, De-Jun; Zhang, Chun-Lin; Gu, Yin-Gang

    2011-12-01

    A 4-day field observation was conducted at Liede sewage treatment plant in Guangzhou, using PFPH/GC/MS method to analyse the composition and the concentration of volatile carbonyl compounds, and investigate the source emission characteristics of the pollutants. The results were as follows: 18 carbonyl species were detected, which including 15 malodorous volatile carbonyls with a concentration range from 0.39 microg x m(-3) to 19.92 microg x m(-3) at six processing units. Mean value of the total malodorous volatile carbonyls was (68.66 +/- 10.05) microg x m(-3). Normalization data process was used to research the source emission profile for malodorous volatile carbonyls, formaldehyde, acetaldehyde, propionaldehyde, 2-butanone, butyraldehyde and hexaldehyde were found to be molecular markers of the source emission with their percentage of total carbonyls up to 78.91%. Hexaldehyde was the most abundant carbonyl species with an average concentration of 11.71 microg x m(-3). Using a calculation model of area source emission, it estimated that the total annual emissions of the municipal sewage treatment plant was 2 302.33 kg(-1), and the contribution ratio of each processing unit was in an order of biochemical reaction basin, concentration basin, grade A aeration, ascending pump room, grit basin, dewatering house. The malodorous emission of sewage treatment plant is affected by many complex factors, so there's some uncertainty on the estimate. PMID:22468520

  1. Variation of ambient carbonyl levels in urban Beijing between 2005 and 2012

    NASA Astrophysics Data System (ADS)

    Chen, Wentai; Shao, Min; Wang, Ming; Lu, Sihua; Liu, Ying; Yuan, Bin; Yang, Yudong; Zeng, Limin; Chen, Zhongming; Chang, Chih-Chung; Zhang, Qian; Hu, Min

    2016-03-01

    Carbonyl compounds are important precursors of secondary air pollutants. With the rapid economic development and the implementation of stricter control measures in Beijing, the sources of carbonyls possibly changed. Based on measurement data obtained at an urban site in Beijing between 2005 and 2012, we investigated annual variations in carbonyl levels and sources during these years. In summer, formaldehyde and acetaldehyde levels decreased significantly at a rate of 9.1%/year and 7.2%/year, respectively, while acetone levels increased at a rate of 4.3%/year. In winter, formaldehyde levels increased and acetaldehyde levels decreased. We also investigated the factors driving the variation in carbonyls levels during summer by determination of emission ratios for carbonyls and their precursors, and calculation of photochemical formation of carbonyls. The relative declines for primary formaldehyde and acetaldehyde levels were larger than those for secondary formation. This is possibly due to the increasing usage of natural gas and liquefied petroleum gas which could result in the rise of carbonyl precursor emission ratios. The increase in acetone levels might be related to the rising solvent usage in Beijing during these years. The influences of these sources should be paid more attention in future research.

  2. Electroless plating preparation and electromagnetic properties of Co-coated carbonyl iron particles/polyimide composite

    NASA Astrophysics Data System (ADS)

    Zhou, Yingying; Zhou, Wancheng; Li, Rong; Qing, Yuchang; Luo, Fa; Zhu, Dongmei

    2016-03-01

    To solve the serious electromagnetic interference problems at elevated temperature, one thin microwave-absorbing sheet employing Co-coated carbonyl iron particles and polyimide was prepared. The Co-coated carbonyl iron particles were successfully prepared using an electroless plating method. The microstructure, composition, phase and static magnetic properties of Co-coated carbonyl iron particles were characterized by combination of scanning electron microscope (SEM), energy dispersive spectrometer (EDS), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The electromagnetic parameters of Co-coated carbonyl iron particles/polyimide composite were measured in the frequency range of 2-18 GHz, and the electromagnetic loss mechanism of the material-obtained was discussed. The microwave absorption properties of composites before and after heat treatment at 300 °C for 100 h were characterized in 2-18 GHz frequency range. It was established that composites based on Co-coated carbonyl iron demonstrate thermomagnetic stability, indicating that Co coating reduces the oxidation of carbonyl iron. Thus, Co-coated carbonyl iron particles/polyimide composites are useful in the design of microwave absorbers operating at temperatures up to 300 °C.

  3. Cytoprotection by almond skin extracts or catechins of hepatocyte cytotoxicity induced by hydroperoxide (oxidative stress model) versus glyoxal or methylglyoxal (carbonylation model).

    PubMed

    Dong, Qiang; Banaich, Monica S; O'Brien, Peter J

    2010-04-29

    Oxidative and carbonyl stress are detrimental in the pathogenesis of diabetic complications, as well as in other chronic diseases. However, this process may be decreased by dietary bioactive compounds. Almond skin is an abundant source of bioactive compounds and antioxidants, including polyphenolic flavonoids, which may contribute to the decrease in oxidative and carbonyl stress. In this study, four Almond Skin Extracts (ASEI, ASEII, ASEIII, and ASEIV) were prepared by different methods and evaluated for their antioxidant activity. The order of the polyphenol content (total muM gallic acid equivalents) of the four extracts was found to be, in decreasing order of effectiveness: ASEI>ASEIII>ASEIV>ASEII. The order of Ferric-reducing antioxidant power (FRAP, microM FeSO(4)/g) value, in decreasing order was ASEI (216)>ASEIII (176)>ASEIV (89)>ASEII (85). The order of ASE effectiveness for decreasing protein carbonyation induced by the copper Fenton reaction was ASEI>ASEIV>ASEII>ASEIII. The order of antioxidant effectiveness for inhibiting tertiary-butyl hydroperoxide (TBH) induced microsomal lipid peroxidation was ASEI>ASEIV>ASEII, ASEIII. Also, the order of ASE effectiveness for inhibiting TBH induced hepatocyte cell death was: ASEIII, ASEIV>ASEI, ASEII. Catechin also protected hepatocytes from TBH induced hepatocyte, lipid peroxidation and cytotoxicity. In a cell free model, equimolar concentrations of catechin or epicatechin rescued serum albumin from protein carbonylation induced by methylglyoxal (MGO). Catechin, epicatechin and ASEI all decreased gloxal induced hepatocyte cell death and reactive oxygen species (ROS) formation in GSH-depleted hepatocytes. Catechin and epicatechin protected against GO or MGO induced hepatocyte cell death, protein carbonylation and ROS formation. Catechin was more effective than epicatechin. Our results suggest that (a) bioactive almond skin constituents in the non-lipophilic polyphenol extract were the most effective at protecting

  4. [Age-dependent characteristics of oxidative stress formation in the liver of rats with hypothyroidism during intensive physical exercise].

    PubMed

    Dzhazaérli, Mokhamad Salem; Davydov, V V

    2006-01-01

    The objective of the present experiment was to study free radical protein oxidation and lipid peroxidation in the liver of 1.5-month-old and 12-month-old rats with drug-induced hypothyroidism caused by exercises. The results of the present study suggest that intensive exercises are accompanied by an increase of intensity of free radical processes in the liver. Hypothyroidism and exercises do not greatly affect free radical processes in the liver of 12-month-old rats but result in additional stimulation of free radical oxidation in subcellular liver fractions of 1.5-month-old rats. An increase of free radical processes in the liver of 1.5-month-old rats with hypothyroidism caused by exercises is associated neither with changes in the first level antioxidant defense system enzymes function, nor with modulation of hepatocytes subcellular sensitivity to prooxidants. Such change is due largely to an increase of free radical production in the liver cells. PMID:17290792

  5. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Vandal, Milene; White, Phillip J; Chevrier, Geneviève; Tremblay, Cyntia; St-Amour, Isabelle; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2015-10-01

    Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple-transgenic (3xTg)-AD mouse model of AD, compared with those in nontransgenic (non-Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical Aβ accumulation (2- and 3.5-fold increase in Aβ42 in the soluble and insoluble protein fractions, respectively) in female 3xTg-AD mice than in the males. Furthermore, female 3xTg-AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non-Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5-fold from 6 to 14 mo of age in female 3xTg-AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg-AD mice. The present results suggest that AD-like neuropathology extends to the pancreas in the 3xTg-AD mouse, leading to glucose intolerance and contributing to a pathologic self-amplifying loop between AD and T2D. PMID:26108977

  6. Claudin-4 undergoes age-dependent change in cellular localization on pig jejunal villous epithelial cells, independent of bacterial colonization.

    PubMed

    Pasternak, J Alex; Kent-Dennis, Coral; Van Kessel, Andrew G; Wilson, Heather L

    2015-01-01

    Newborn piglets are immunologically naïve and must receive passive immunity via colostrum within 24 hours to survive. Mechanisms by which the newborn piglet gut facilitates uptake of colostral cells, antibodies, and proteins may include FcRn and pIgR receptor-mediated endocytosis and paracellular transport between tight junctions (TJs). In the present study, FcRn gene (FCGRT) was minimally expressed in 6-week-old gut and newborn jejunum but it was expressed at significantly higher levels in the ileum of newborn piglets. pIgR was highly expressed in the jejunum and ileum of 6-week-old animals but only minimally in neonatal gut. Immunohistochemical analysis showed that Claudin-5 localized to blood vessel endothelial cells. Claudin-4 was strongly localized to the apical aspect of jejunal epithelial cells for the first 2 days of life after which it was redistributed to the lateral surface between adjacent enterocytes. Claudin-4 was localized to ileal lateral surfaces within 24 hours after birth indicating regional and temporal differences. Tissue from gnotobiotic piglets showed that commensal microbiota did not influence Claudin-4 surface localization on jejunal or ileal enterocytes. Regulation of TJs by Claudin-4 surface localization requires further investigation. Understanding the factors that regulate gut barrier maturation may yield protective strategies against infectious diseases. PMID:25948883

  7. Decline in Age-dependent, MK801-induced Injury Coincides With Developmental Switch in Parvalbumin Expression: Somatosensory and Motor Cortex

    PubMed Central

    Tomé, Carla M Lema; Miller, Ryan; Bauer, Clayton; Smith, Chelsey; Blackstone, Kaitlin; Leigh, Adam; Busch, Jamie; Turner, Christopher P

    2009-01-01

    MK801-induced activation of caspase-3 is developmentally regulated, peaking at postnatal day (P) 7 and decreasing with increasing postnatal age thereafter. Further, at P7, cells displaying activation of caspase-3 lack expression of calcium binding proteins (CaBPs). To further explore this relationship, we investigated postnatal expression of calbindin (CB), calretinin (CR) and parvalbumin (PV) in two brain regions susceptible to MK801-induced injury, the somatosensory cortex (S1) and layer II/III of motor cortex (M1/M2). Expression of CB and especially PV was low to absent prior to P7 but substantially increased from P7 through to P21 and adulthood. In contrast, CR expression was more variable at early developmental ages, stabilized to lower levels after P7 and showed a marked decline by P21. The results suggest that not only does calcium buffering capacity increase developmentally but acquisition of enhanced buffering may be one mechanism by which neurons survive agent-induced alterations in calcium homeostasis. PMID:18688810

  8. Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine

    PubMed Central

    Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja; Nabi, Rafiq; Kozlowski, Pamela A.; Montefiori, David C.; LaBranche, Celia C.; Wrammert, Jens; Keele, Brandon F.; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Santra, Sampa; Basu, Rahul; Moss, Bernard; Robinson, Harriet L.; Amara, Rama Rao

    2016-01-01

    Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods. The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results. Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions. The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques. PMID:27006959

  9. Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts.

    PubMed

    Bowman, Amy; Birch-Machin, Mark A

    2016-05-01

    The mitochondrial theory of aging remains one of the most widely accepted aging theories and implicates mitochondrial electron transport chain dysfunction with subsequent increasing free radical generation. Recently, complex II of the electron transport chain appears to be more important than previously thought in this process, suggested predominantly by nonhuman studies. We investigated the relationship between complex II and aging using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering a wide age range. Complex II activity significantly decreased with age in fibroblasts (P = 0.015) but not in keratinocytes. This was associated with a significant decline in transcript expression (P = 0.008 and P = 0.001) and protein levels (P = 0.0006 and P = 0.005) of the succinate dehydrogenase complex subunit A and subunit B catalytic subunits of complex II, respectively. In addition, there was a significant decrease in complex II activity with age (P = 0.029) that was specific to senescent skin cells. There was no decrease in complex IV activity with increasing age, suggesting possible locality to complex II. PMID:26829036

  10. Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.

    PubMed

    Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja; Nabi, Rafiq; Kozlowski, Pamela A; Montefiori, David C; LaBranche, Celia C; Wrammert, Jens; Keele, Brandon F; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Santra, Sampa; Basu, Rahul; Moss, Bernard; Robinson, Harriet L; Amara, Rama Rao

    2016-01-01

    Background.  In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods.  The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results.  Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)α-permissive rhesus macaques showed an 80% reduction in per-exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions.  The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques. PMID:27006959

  11. Genomewide analysis of Drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation

    PubMed Central

    Westholm, Jakub O.; Miura, Pedro; Olson, Sara; Shenker, Sol; Joseph, Brian; Sanfilippo, Piero; Celniker, Susan E.; Graveley, Brenton R.; Lai, Eric C.

    2014-01-01

    Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues and cultured cells, to rigorously annotate >2500 fruitfly circular RNAs. These mostly derive from back-splicing of protein-coding genes and lack poly(A) tails, and circularization of hundreds of genes is conserved across multiple Drosophila species. We elucidate structural and sequence properties of Drosophila circular RNAs, which exhibit commonalities and distinctions from mammalian circles. Notably, Drosophila circular RNAs harbor >1000 well-conserved canonical miRNA seed matches, especially within coding regions, and coding conserved miRNA sites reside preferentially within circularized exons. Finally, we analyze the developmental and tissue specificity of circular RNAs, and note their preferred derivation from neural genes and enhanced accumulation in neural tissues. Interestingly, circular isoforms increase dramatically relative to linear isoforms during CNS aging, and constitute a novel aging biomarker. PMID:25544350

  12. Combinational losses of synucleins reveal their differential requirements for compensating age-dependent alterations in motor behavior and dopamine metabolism.

    PubMed

    Connor-Robson, Natalie; Peters, Owen M; Millership, Steven; Ninkina, Natalia; Buchman, Vladimir L

    2016-10-01

    Synucleins are involved in multiple steps of the neurotransmitter turnover, but the largely normal synaptic function in young adult animals completely lacking synucleins suggests their roles are dispensable for execution of these processes. Instead, they may be utilized for boosting the efficiency of certain molecular mechanisms in presynaptic terminals, with a deficiency of synuclein proteins sensitizing to or exacerbating synaptic malfunction caused by accumulation of mild alterations, which are commonly associated with aging. Although functional redundancy within the family has been reported, it is unclear whether the remaining synucleins can fully compensate for the deficiency of a lost family member or whether some functions are specific for a particular member. We assessed several structural and functional characteristics of the nigrostriatal system of mice lacking members of the synuclein family in every possible combination and demonstrated that stabilization of the striatal dopamine level depends on the presence of α-synuclein and cannot be compensated by other family members, whereas β-synuclein is required for efficient maintenance of animal's balance and coordination in old age. PMID:27614017

  13. Claudin-4 Undergoes Age-Dependent Change in Cellular Localization on Pig Jejunal Villous Epithelial Cells, Independent of Bacterial Colonization

    PubMed Central

    Van Kessel, Andrew G.; Wilson, Heather L.

    2015-01-01

    Newborn piglets are immunologically naïve and must receive passive immunity via colostrum within 24 hours to survive. Mechanisms by which the newborn piglet gut facilitates uptake of colostral cells, antibodies, and proteins may include FcRn and pIgR receptor-mediated endocytosis and paracellular transport between tight junctions (TJs). In the present study, FcRn gene (FCGRT) was minimally expressed in 6-week-old gut and newborn jejunum but it was expressed at significantly higher levels in the ileum of newborn piglets. pIgR was highly expressed in the jejunum and ileum of 6-week-old animals but only minimally in neonatal gut. Immunohistochemical analysis showed that Claudin-5 localized to blood vessel endothelial cells. Claudin-4 was strongly localized to the apical aspect of jejunal epithelial cells for the first 2 days of life after which it was redistributed to the lateral surface between adjacent enterocytes. Claudin-4 was localized to ileal lateral surfaces within 24 hours after birth indicating regional and temporal differences. Tissue from gnotobiotic piglets showed that commensal microbiota did not influence Claudin-4 surface localization on jejunal or ileal enterocytes. Regulation of TJs by Claudin-4 surface localization requires further investigation. Understanding the factors that regulate gut barrier maturation may yield protective strategies against infectious diseases. PMID:25948883

  14. Characteristics of carbonyls: Concentrations and source strengths for indoor and outdoor residential microenvironments in China

    NASA Astrophysics Data System (ADS)

    Wang, B.; Lee, S. C.; Ho, K. F.

    Indoor and outdoor carbonyl concentrations were measured simultaneously in 12 urban dwellings in Beijing, Shanghai, Guangzhou, and Xi'an, China in summer (from July to September in 2004) and winter (from December 2004 to February 2005). Formaldehyde was the most abundant indoor carbonyls species, while formaldehyde, acetaldehyde and acetone were found to be the most abundant outdoor carbonyls species. The average formaldehyde concentrations in summer indoor air varied widely between cities, ranging from a low of 19.3 μg m -3 in Xi'an to a high of 92.8 μg m -3 in Beijing. The results showed that the dwellings with tobacco smoke, incense burning or poor ventilation had significantly higher indoor concentrations of certain carbonyls. It was noticed that although one half of the dwellings in this study installed with low emission building materials or furniture, the carbonyls levels were still significantly high. It was also noted that in winter both the indoor and outdoor acetone concentrations in two dwellings in Guangzhou were significantly high, which were mainly caused by the usage of acetone as industrial solvent in many paint manufacturing and other industries located around Guangzhou and relatively longer lifetime of acetone for removal by photolysis and OH reaction than other carbonyls species. The indoor carbonyls levels in Chinese dwellings were higher than that in dwellings in the other countries. The levels of indoor and ambient carbonyls showed great seasonal differences. Six carbonyls species were carried out the estimation of indoor source strengths. Formaldehyde had the largest indoor source strength, with an average of 5.25 mg h -1 in summer and 1.98 mg h -1 in winter, respectively. However, propionaldehyde, crotonaldehyde and benzaldehyde had the weakest indoor sources.

  15. Multiple abiotic stress tolerance in Vigna mungo is altered by overexpression of ALDRXV4 gene via reactive carbonyl detoxification.

    PubMed

    Singh, Preeti; Kumar, Deepak; Sarin, Neera Bhalla

    2016-06-01

    Vigna mungo (blackgram) is an important leguminous pulse crop, which is grown for its protein rich edible seeds. Drought and salinity are the major abiotic stresses which adversely affect the growth and productivity of crop plants including blackgram. The ALDRXV4 belongs to the aldo-keto reductase superfamily of enzymes that catalyze the reduction of carbonyl metabolites in the cells and plays an important role in the osmoprotection and detoxification of the reactive carbonyl species. In the present study, we developed transgenic plants of V. mungo using Agrobacterium mediated transformation. The transgene integration was confirmed by Southern blot analysis whereas the expression was confirmed by RT-PCR, Western blot and enzyme activity. The T1 generation transgenic plants displayed improved tolerance to various environmental stresses, including drought, salt, methyl viologen and H2O2 induced oxidative stress. The increased aldose reductase activity, higher sorbitol content and less accumulation of the toxic metabolite, methylglyoxal in the transgenic lines under non-stress and stress (drought and salinity) conditions resulted in increased protection through maintenance of better photosynthetic efficiency, higher relative water content and less photooxidative damage. The accumulation of reactive oxygen species was remarkably decreased in the transgenic lines as compared with the wild type plants. This study of engineering multiple stress tolerance in blackgram, is the first report to date and this strategy for trait improvement is proposed to provide a novel germplasm for blackgram production on marginal lands. PMID:26956699

  16. Engineering of a novel carbonyl reductase with coenzyme regeneration in E. coli for efficient biosynthesis of enantiopure chiral alcohols.

    PubMed

    Wei, Ping; Gao, Jia-Xin; Zheng, Gao-Wei; Wu, Hong; Zong, Min-Hua; Lou, Wen-Yong

    2016-07-20

    The novel anti-Prelog stereospecific carbonyl reductase from Acetobacter sp. CCTCC M209061 was successfully expressed in E. coli combined with glucose dehydrogenase (GDH) to construct an efficient whole-cell biocatalyst with coenzyme NADH regeneration. The enzymatic activity of GAcCR (AcCR with a GST tag) reached 304.9U/g-dcw, even 9 folds higher than that of wild strain, and the activity of GDH for NADH regeneration recorded 46.0U/mg-protein in the recombinant E. coli. As a whole-cell biocatalyst, the recombinant E. coli BL21(DE3)pLysS (pETDuet-gaccr-gdh) possessed a broad substrate spectrum for kinds of carbonyl compounds with encouraging yield and stereoselectivity. Besides, the asymmetric reduction of ethyl 4-chloroacetoacetate (COBE) to optically pure ethyl 4-chloro-3-hydroxybutyrate (CHBE) catalyzed by the whole-cell biocatalyst was systematically investigated. Under the optimal reaction conditions, the optical purity of CHBE was over 99% e.e. for (S)-enantiomer, and the initial rate and product yield reached 8.04μmol/min and 99.4%, respectively. Moreover, the space-time yield was almost 20 folds higher than that catalyzed by the wild strain. Therefore, a new, high efficiency biocatalyst for asymmetric reductions was constructed successfully, and the enantioselective reduction of prochiral compounds using the biocatalyst was a promising approach for obtaining enantiopure chiral alcohols. PMID:27211999

  17. Extraction of dielectric and magnetic properties of carbonyl iron powder composites at high frequencies

    NASA Astrophysics Data System (ADS)

    Zivkovic, I.; Murk, A.

    2012-06-01

    In this paper, we examine carbonyl iron composites in silicone rubber and epoxy matrices. Transmission measurements were performed at W (70 to 110 GHz) and Ka (26 to 40 GHz) bands and effective permittivity and permeability of composites with 10% volume fraction of carbonyl iron powder (CIP) were extracted at these frequencies. To extract permittivity and permeability of carbonyl iron powder in W and Ka bands, we use Looyenga formula. We extract permittivity and permeability of CIP from both silicone rubber and epoxy based composites and good agreement is achieved.

  18. A Convenient Palladium-Catalyzed Reductive Carbonylation of Aryl Iodides with Dual Role of Formic Acid.

    PubMed

    Qi, Xinxin; Li, Chong-Liang; Wu, Xiao-Feng

    2016-04-18

    Palladium-catalyzed reductive carbonylation of aryl halides represents a straightforward pathway for the synthesis of aromatic aldehydes. The known reductive carbonylation procedures either require CO gas or complexed compounds as CO sources. In this communication, we developed a palladium-catalyzed reductive carbonylation of aryl iodides with formic acid as the formyl source. As a convenient, practical, and environmental friendly methodology, no additional silane or H2 was required. A variety of aromatic aldehydes were isolated in moderate to excellent yields under mild reaction conditions. Notably, this is the first procedure on using formic acid as the formyl source. PMID:26934464

  19. Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism.

    PubMed

    Friedl, Gerald; Turner, Russell T; Evans, Glenda L; Dobnig, Harald

    2007-11-01

    In recent years, intermittent PTH treatment has been investigated extensively for its efficacy in preventing osteoporotic fractures and to improve fracture healing and implant fixation. Although these tasks concern patients of all ages, very little is known about whether aging impacts the bone anabolic response to PTH. Female Sprague-Dawley rats of 1, 3, and 13 months of age were either treated by hPTH-(1-34) or by vehicle solution (CTR) for 1 week. As main outcome measures, we determined the effects on static and dynamic histomorphometry of cancellous bone. In addition, we measured gene expression in femur and serum parameters reflecting bone turnover and mineral metabolism. There was a profound decrease in bone formation rate (BFR) with aging in CTR rats, whereas PTH treatment resulted in a significant relative 1.5-, 3-, and 4.7-fold increase in BFR, without altering indices of bone resorption. Aging decreased and PTH increased mRNA levels for bone matrix proteins and growth factors in a gene-specific manner. In younger animals, PTH-induced a marked stimulation in the mineral apposition rate with no effect on osteoblast number, whereas the latter was increased in older animals (1.0-, 1.7-, and 3.1-fold). Treatment with PTH in young rats led to a significant increase in trabecular number (1.6-2.6/mm, p < 0.05), whereas older rats demonstrated increases in trabecular thickness only (52.8-77.8 microm, p < 0.001). Although PTH increased bone formation at all ages, we found significant age-related differences in the cellular and molecular mechanisms involved in the bone anabolic response to the hormone. PMID:17557320

  20. Protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Proteins are the major structural and functional components of all cells in the body. They are macromolecules that comprise 1 or more chains of amino acids that vary in their sequence and length and are folded into specific 3-dimensional structures. The sizes and conformations of proteins, therefor...