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Sample records for inactive arylsulphatase mutants

  1. An Inactive Geminin Mutant That Binds Cdt1

    PubMed Central

    Suchyta, Marissa; Miotto, Benoit; McGarry, Thomas J.

    2015-01-01

    The initiation of DNA replication is tightly regulated in order to ensure that the genome duplicates only once per cell cycle. In vertebrate cells, the unstable regulatory protein Geminin prevents a second round of DNA replication by inhibiting the essential replication factor Cdt1. Cdt1 recruits mini-chromosome maintenance complex (MCM2-7), the replication helicase, into the pre-replication complex (pre-RC) at origins of DNA replication. The mechanism by which Geminin inhibits MCM2-7 loading by Cdt1 is incompletely understood. The conventional model is that Geminin sterically hinders a direct physical interaction between Cdt1 and MCM2-7. Here, we describe an inactive missense mutant of Geminin, GemininAWA, which binds to Cdt1 with normal affinity yet is completely inactive as a replication inhibitor even when added in vast excess. In fact, GemininAWA can compete with GemininWT for binding to Cdt1 and prevent it from inhibiting DNA replication. GemininAWA does not inhibit the loading of MCM2-7 onto DNA in vivo, and in the presence of GemininAWA, nuclear DNA is massively over-replicated within a single S phase. We conclude that Geminin does not inhibit MCM loading by simple steric interference with a Cdt1-MCM2-7 interaction but instead works by a non-steric mechanism, possibly by inhibiting the histone acetyltransferase HBO1. PMID:25988259

  2. LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition.

    PubMed

    Cuevas, Eva P; Moreno-Bueno, Gema; Canesin, Giacomo; Santos, Vanesa; Portillo, Francisco; Cano, Amparo

    2014-01-01

    Lysyl-oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family that catalyzes the cross-linking of collagens or elastins in the extracellular matrix, thus regulating the tensile strength of tissues. However, many reports have suggested different intracellular roles for LOXL2, including the ability to regulate gene transcription and tumor progression. We previously reported that LOXL2 mediates epithelial-to-mesenchymal transition (EMT) by Snail1-dependent and independent mechanisms, related to E-cadherin silencing and downregulation of epidermal differentiation and cell polarity components, respectively. Whether or not the catalytic activity of LOXL2 is required to induce/sustain EMT is actually unknown. Here we show that LOXL2 catalytic inactive mutants collaborate with Snail1 in E-cadherin gene repression to trigger EMT and, in addition, promote FAK/Src pathway activation to support EMT. These findings reveal a non-conventional role of LOXL2 on regulating epithelial cell plasticity. PMID:24414204

  3. A role for protein kinase CK2 in cell proliferation: evidence using a kinase-inactive mutant of CK2 catalytic subunit alpha.

    PubMed

    Lebrin, F; Chambaz, E M; Bianchini, L

    2001-04-12

    Protein kinase CK2 is an ubiquitous and pleiotropic Ser/Thr protein kinase composed of two catalytic (alpha and/or alpha') and two regulatory (beta) subunits generally combined to form alpha(2)beta(2), alphaalpha'beta(2), or alpha'(2)beta(2) heterotetramers. To gain more insight into the role of CK2 in the control of proliferation in mammalian cells, overexpression of isolated CK2 subunits alpha, alpha', or beta was carried out in two fibroblast cell lines: NIH3T3 and CCL39. To interfere with CK2 cellular functions, cells were also transfected with a kinase-inactive mutant of CK2alpha catalytic subunit: CK2alpha-K68A. In NIH3T3 cells, overexpression of either wild-type subunit (alpha, alpha' or beta) had no effect on cell proliferation. In contrast, overexpression of the CK2alpha kinase-deficient mutant induced a marked inhibition of cell proliferation. This resulted from a defect in G1/S progression as demonstrated in transient transfection experiments in both NIH3T3 and CCL39 cells using BrdU incorporation measurements and in CCL39 clones stably overexpressing the CK2alpha-K68A mutant by growth curve analysis. We demonstrated that the kinase-negative mutant has the capacity to integrate the endogenous CK2 subunit pool both as an isolated kinase-inactive alpha subunit and as associated to the beta subunit in a kinase-inactive tetramer. Finally we showed that expression of the kinase-inactive mutant interferes with phosphorylation of an endogenous CK2 substrate; we speculate that optimal phosphorylation of target proteins by CK2 is required to achieve optimal cell cycle progression. PMID:11360185

  4. Arylsulphatase activity and sulphate content in relation to crop rotation and fertilization of soil

    NASA Astrophysics Data System (ADS)

    Siwik-Ziomek, Anetta; Lemanowicz, Joanna; Koper, Jan

    2016-07-01

    The aim of the study was to investigate the effect of varying rates of FYM (0, 20, 40, 60 Mg ha-1) and nitrogen N0, N1, N2, and N3 on the content of sulphate sulphur (VI) and the activity of arylsulphatase, which participates in the transformations of this element in Haplic Luvisol. The study report is based on a long-term field experiment with two different crop rotations: A - recognized as exhausting the humus from soil and B - recognized as enriching the soil with humus. During the cultivation of the plants, the soil was sampled four times from corn and a red clover cultivar and grass. The FYM fertilization rate for which the highest arylsulphatase activity and the content of sulphates were identified was 60 Mg ha-1. An inhibitory effect of high rates (90 and 135 kg N ha-1) of ammonium nitrate on the arylsulphatase activity was also observed. A significant correlation between the content of carbon, nitrogen, and sulphates and the arylsulphatase activity was recorded. The investigation on the effect of combined application of farmyard manure and mineral nitrogen fertilization on the activity of arylsulphatase participating in the sulphur cycling was launched to examine the problem in detail.

  5. Generation and deposition of Aβ43 by the virtually inactive presenilin-1 L435F mutant contradicts the presenilin loss-of-function hypothesis of Alzheimer's disease.

    PubMed

    Kretner, Benedikt; Trambauer, Johannes; Fukumori, Akio; Mielke, Janina; Kuhn, Peer-Hendrik; Kremmer, Elisabeth; Giese, Armin; Lichtenthaler, Stefan F; Haass, Christian; Arzberger, Thomas; Steiner, Harald

    2016-01-01

    As stated by the prevailing amyloid cascade hypothesis, Alzheimer's disease (AD) is caused by the aggregation and cerebral deposition of long amyloid-β peptide (Aβ) species, which are released from a C-terminal amyloid precursor protein fragment by γ-secretase. Mutations in its catalytic subunit presenilin-1 (PS1) increase the Aβ42 to Aβ40 ratio and are the major cause of familial AD (FAD). An opposing hypothesis states that loss of essential presenilin functions underlies the disease. A major argument for this hypothesis is the observation that the nearly inactive PS1 L435F mutant, paradoxically, causes FAD We now show that the very little Aβ generated by PS1 L435F consists primarily of Aβ43, a highly amyloidogenic species which was overlooked in previous studies of this mutant. We further demonstrate that the generation of Aβ43 is not due to a trans-dominant effect of this mutant on WT presenilin. Furthermore, we found Aβ43-containing plaques in brains of patients with this mutation. The aberrant generation of Aβ43 by this particular mutant provides a direct objection against the presenilin hypothesis. PMID:26988102

  6. Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages.

    PubMed Central

    Muschol, Nicole; Matzner, Ulrich; Tiede, Stephan; Gieselmann, Volkmar; Ullrich, Kurt; Braulke, Thomas

    2002-01-01

    The transfer of macrophage-secreted arylsulphatase A (ASA) to enzyme-deficient brain cells is part of the therapeutic concept of bone marrow transplantation in lysosomal storage diseases. Here we have investigated this transfer in vitro. The uptake of (125)I-labelled recombinant human ASA purified from ASA-overexpressing mouse embryonic fibroblasts deficient for mannose 6-phosphate (M6P) receptors in a mouse ASA-deficient astroglial cell line was completely inhibited by M6P. In contrast, when ASA-deficient astroglial cells were incubated with secretions of [(35)S]methionine-labelled human macrophages or mouse microglia, containing various lysosomal enzymes, neither ASA nor cathepsin D (CTSD) were detected in acceptor cells. Co-culturing of metabolically labelled macrophages with ASA-deficient glial cells did not result in an M6P-dependent transfer of ASA or CTSD between these two cell types. In secretions of [(33)P]phosphate-labelled macrophages no or weakly phosphorylated ASA and CTSD precursor polypeptides were found, whereas both intracellular and secreted ASA from ASA-overexpressing baby hamster kidney cells displayed (33)P-labelled M6P residues. Finally, the uptake of CTSD from secretions of [(35)S]methionine-labelled macrophages in rat hepatocytes was M6P-independent. These data indicated that lysosomal enzymes secreted by human macrophages or a mouse microglial cell line cannot be endocytosed by brain cells due to the failure to equip newly synthesized lysosomal enzymes with the M6P recognition marker efficiently. The data suggest that other mechanisms than the proposed M6P-dependent secretion/recapture of lysosomal enzymes might be responsible for therapeutic effects of bone marrow transplantation in the brain. PMID:12296771

  7. Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages.

    PubMed

    Muschol, Nicole; Matzner, Ulrich; Tiede, Stephan; Gieselmann, Volkmar; Ullrich, Kurt; Braulke, Thomas

    2002-12-15

    The transfer of macrophage-secreted arylsulphatase A (ASA) to enzyme-deficient brain cells is part of the therapeutic concept of bone marrow transplantation in lysosomal storage diseases. Here we have investigated this transfer in vitro. The uptake of (125)I-labelled recombinant human ASA purified from ASA-overexpressing mouse embryonic fibroblasts deficient for mannose 6-phosphate (M6P) receptors in a mouse ASA-deficient astroglial cell line was completely inhibited by M6P. In contrast, when ASA-deficient astroglial cells were incubated with secretions of [(35)S]methionine-labelled human macrophages or mouse microglia, containing various lysosomal enzymes, neither ASA nor cathepsin D (CTSD) were detected in acceptor cells. Co-culturing of metabolically labelled macrophages with ASA-deficient glial cells did not result in an M6P-dependent transfer of ASA or CTSD between these two cell types. In secretions of [(33)P]phosphate-labelled macrophages no or weakly phosphorylated ASA and CTSD precursor polypeptides were found, whereas both intracellular and secreted ASA from ASA-overexpressing baby hamster kidney cells displayed (33)P-labelled M6P residues. Finally, the uptake of CTSD from secretions of [(35)S]methionine-labelled macrophages in rat hepatocytes was M6P-independent. These data indicated that lysosomal enzymes secreted by human macrophages or a mouse microglial cell line cannot be endocytosed by brain cells due to the failure to equip newly synthesized lysosomal enzymes with the M6P recognition marker efficiently. The data suggest that other mechanisms than the proposed M6P-dependent secretion/recapture of lysosomal enzymes might be responsible for therapeutic effects of bone marrow transplantation in the brain. PMID:12296771

  8. Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI

    PubMed Central

    Uttarilli, Anusha; Ranganath, Prajnya; Jain, S. Jamal Md Nurul; Krishna, Prasad C.; Sinha, Anupam; Verma, Ishwar C.; Phadke, Shubha R.; Puri, Ratna D.; Danda, Sumita; Muranjan, Mamta N.; Jevalikar, Ganesh; Nagarajaram, H. A.; Dalal, Ashwin B.

    2015-01-01

    Background & objectives: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase resulting from mutations in the arylsulphatase B (ARSB) gene. The ARSB gene is located on chromosome 5q11-q13 and is composed of eight exons. More than hundred ARSB mutations have been reported so far, but the mutation spectrum of MPS VI in India is still unknown. Hence, the aim of the present study was to identify the mutational spectrum in patients with MPS VI in India and to study the genotype-phenotype association and functional outcomes of these mutations. Methods: Molecular characterization of the ARSB gene by Sanger sequencing was done for 15 patients (aged 15 months to 11 yr) who were enzymatically confirmed to have MPS VI. Age of onset, clinical progression and enzyme activity levels in each patient were studied to look for genotype-phenotype association. Haplotype analysis performed for unrelated patients with the recurring mutation W450C, was suggestive of a founder effect. Sequence and structural analyses of the ARSB protein using standard software were carried out to determine the impact of detected mutations on the function of the ARSB protein. Results: A total of 12 mutations were identified, of which nine were novel mutations namely, p.D53N, p.L98R, p.Y103SfsX9, p.W353X, p.H393R, p.F166fsX18, p.I220fsX5, p.W450L, and p.W450C, and three were known mutations (p.D54N, p.A237D and p.S320R). The nine novel sequence variants were confirmed not to be polymorphic variants by performing sequencing in 50 unaffected individuals from the same ethnic population. Interpretation & conclusions: Nine novel mutations were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI. PMID:26609033

  9. Structure of solvation water around the active and inactive regions of a type III antifreeze protein and its mutants of lowered activity.

    PubMed

    Grabowska, Joanna; Kuffel, Anna; Zielkiewicz, Jan

    2016-08-21

    Water molecules from the solvation shell of the ice-binding surface are considered important for the antifreeze proteins to perform their function properly. Herein, we discuss the problem whether the extent of changes of the mean properties of solvation water can be connected with the antifreeze activity of the protein. To this aim, the structure of solvation water of a type III antifreeze protein from Macrozoarces americanus (eel pout) is investigated. A wild type of the protein is used, along with its three mutants, with antifreeze activities equal to 54% or 10% of the activity of the native form. The solvation water of the ice-binding surface and the rest of the protein are analyzed separately. To characterize the structure of solvation shell, parameters describing radial and angular characteristics of the mutual arrangement of the molecules were employed. They take into account short-distance (first hydration shell) or long-distance (two solvation shells) effects. The obtained results and the comparison with the results obtained previously for a hyperactive antifreeze protein from Choristoneura fumiferana lead to the conclusion that the structure and amino acid composition of the active region of the protein evolved to achieve two goals. The first one is the modification of the properties of the solvation water. The second one is the geometrical adjustment of the protein surface to the specific crystallographic plane of ice. Both of these goals have to be achieved simultaneously in order for the protein to perform its function properly. However, they seem to be independent from one another in a sense that very small antifreeze activity does not imply that properties of water become different from the ones observed for the wild type. The proteins with significantly lower activity still modify the mean properties of solvation water in a right direction, in spite of the fact that the accuracy of the geometrical match with the ice lattice is lost because of the

  10. Exercise Responses after Inactivity

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    1986-01-01

    The exercise response after bed rest inactivity is a reduction in the physical work capacity and is manifested by significant decreases in oxygen uptake. The magnitude of decrease in maximal oxygen intake V(dot)O2max is related to the duration of confinement and the pre-bed-rest level of aerobic fitness; these relationships are relatively independent of age and gender. The reduced exercise performance and V(dot)O2max following bed rest are associated with various physiological adaptations including reductions in blood volume, submaximal and maximal stroke volume, maximal cardiac output, sceletal muscle tone and strength, and aerobic enzyme capacities, as well as increases in venous compliance and submaximal and maximal heart rate. This reduction in physiological capacity can be partially restored by specific countermeasures that provide regular muscular activity or orhtostatic stress or both during the bed rest exposure. The understanding of these physiological and physical responses to exercise following bed rest inactivity has important implications for the solution to safety and health problems that arise in clinical medicine, aerospace medicine, sedentary living, and aging.

  11. [Health hazards of physical inactivity].

    PubMed

    Helajärvi, Harri; Lindholm, Harri; Vasankari, Tommi; Heinonen, Olli J

    2015-01-01

    Obesity and non-communicable diseases and related costs increase with physical inactivity. In addition to the lack of recreational exercise, a sedentary lifestyle also seems to have a negative effect of health, independently of other lifestyle and risks. New means, as well as multidisciplinary and multiprofessional collaboration, are required in order to improve health and well-being on the population level and to reduce health-related costs. New, more effective operational models are also needed in health communication in order to achieve the desired and more permanent results. PMID:26591649

  12. 21 CFR 201.117 - Inactive ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Inactive ingredients. 201.117 Section 201.117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.117 Inactive ingredients. A...

  13. 21 CFR 201.117 - Inactive ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Inactive ingredients. 201.117 Section 201.117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.117 Inactive ingredients. A...

  14. Regrets of Action and Inaction across Cultures.

    ERIC Educational Resources Information Center

    Gilovich, Thomas; Wang, Ranxiao Frances; Regan, Dennis; Nishina, Sadafumi

    2003-01-01

    Conducted five studies in three cultures considered less individualistic than the United States (China, Japan, and Russia) to investigate regrets related to action and inaction in people's lives. Respondents in all three cultures tended to regret inactions more than actions in the long term. Types of regrets (generally involving the self rather…

  15. Obesity and Physical Inactivity in Rural America

    ERIC Educational Resources Information Center

    Patterson, Paul Daniel; Moore, Charity G.; Probst, Janice C.; Shinogle, Judith Ann

    2004-01-01

    Context and Purpose: Obesity and physical inactivity are common in the United States, but few studies examine this issue within rural populations. The present study uses nationally representative data to study obesity and physical inactivity in rural populations. Methods: Data came from the 1998 National Health Interview Survey Sample Adult and…

  16. 29 CFR 1404.6 - Inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Inactive status. 1404.6 Section 1404.6 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE ARBITRATION SERVICES Roster of Arbitrators; Admission and Retention § 1404.6 Inactive status. A member of the Roster who continues to...

  17. Health and economic costs of physical inactivity.

    PubMed

    Kruk, Joanna

    2014-01-01

    Physical inactivity has reached epidemic levels in developed countries and is being recognized as a serious public health problem. Recent evidence shows a high percentages of individuals worldwide who are physically inactive, i.e. do not achieve the WHO's present recommendation of 150 minutes of moderate to vigorous intensity per week in addition to usual activities. Living in sedentary lifestyle is one of the leading causes of deaths and a high risk factor for several chronic diseases, like cancer, cardiovascular disease, diabetes type 2, and osteoporosis. This article summarizes evidence for relative risk of the civilization diseases attributable to physical inactivity and the most important conclusions available from the recent investigations computing the economic costs specific to physical inactivity. The findings provide health and economic arguments needed for people to understand the meaning of a sedentary lifestyle. This may be also useful for public health policy in the creation of programmes for prevention of physical inactivity. PMID:25292019

  18. Temperature-Compensating Inactive Strain Gauge

    NASA Technical Reports Server (NTRS)

    Moore, Thomas C., Sr.

    1993-01-01

    Thermal contribution to output of active gauge canceled. High-temperature strain gauges include both active gauge wires sensing strains and inactive gauge wires providing compensation for thermal contributions to gauge readings. Inactive-gauge approach to temperature compensation applicable to commercially available resistance-type strain gauges operating at temperatures up to 700 degrees F and to developmental strain gauges operating at temperatures up to 2,000 degrees F.

  19. Neuromuscular adaptations to respiratory muscle inactivity

    PubMed Central

    Mantilla, Carlos B.; Sieck, Gary C.

    2009-01-01

    Cervical spinal cord injury results in significant functional impairment. It is important to understand the neuroplasticity in response to inactivity of respiratory muscles in order to prevent any associated effects that limit functional recovery. Recent studies have examined the mechanisms involved in inactivity-induced neuroplasticity of diaphragm motor units. Both spinal hemisection at C2 (C2HS) and tetrodotoxin (TTX)-induced phrenic nerve blockade result in diaphragm paralysis and inactivity of axon terminals. However, phrenic motoneurons are inactive with C2HS but remain active after TTX. Diaphragm muscle fibers ipsilateral to C2HS display minimal changes post-injury. Neuromuscular transmission is enhanced following C2HS but impaired following TTX. Synaptic vesicle pool size at diaphragm neuromuscular junctions increases after C2HS, but decreases after TTX. Thus, inactivity-induced neuromuscular plasticity reflects specific adaptations that depend on inactivity at the motoneuron rather than at axon terminals or muscle fibers. Theses results indicate that neuromuscular transmission and functional properties of DIAm fibers can be maintained after spinal cord injury, providing a substrate for functional recovery and/or specific therapeutic approaches such as phrenic pacing. PMID:19744580

  20. Cloning, preparation and preliminary crystallographic studies of penicillin V acylase autoproteolytic processing mutants

    SciTech Connect

    Chandra, P. Manish; Brannigan, James A.; Prabhune, Asmita; Pundle, Archana; Turkenburg, Johan P.; Dodson, G. Guy; Suresh, C. G.

    2005-01-01

    The production, crystallization and characterization of three inactive mutants of penicillin V acylase from B. sphaericus in their respective precursor and processed forms are reported. The space groups are different for the native enzyme and the mutants. The crystallization of three catalytically inactive mutants of penicillin V acylase (PVA) from Bacillus sphaericus in precursor and processed forms is reported. The mutant proteins crystallize in different primitive monoclinic space groups that are distinct from the crystal forms for the native enzyme. Directed mutants and clone constructs were designed to study the post-translational autoproteolytic processing of PVA. The catalytically inactive mutants will provide three-dimensional structures of precursor PVA forms, plus open a route to the study of enzyme–substrate complexes for this industrially important enzyme.

  1. 24 CFR 214.200 - Inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Inactive status. 214.200 Section 214.200 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND...

  2. Dominant lethality by expression of a catalytically inactive class I tRNA synthetase.

    PubMed Central

    Schmidt, E; Schimmel, P

    1993-01-01

    Alignment-guided mutagenesis was used to create an inactive, but toxic, aminoacyl-tRNA synthetase. An Asp-96-->Ala (D96A) replacement in the nucleotide binding fold of the class I Escherichia coli isoleucyl-tRNA synthetase inactivates the enzyme without disrupting its competence for binding isoleucine tRNA. Expression of plasmid-encoded mutant enzyme in a cell with a wild-type ileS chromosomal allele resulted in cell death. Introduction of a second K732T substitution previously shown to weaken tRNA binding gives an inactive D96A/K732T double mutant. Expression of the double mutant is not lethal to E. coli. D96A but not the double mutant significantly inhibited in vitro charging of isoleucine tRNA by the wild-type enzyme. The results suggest a dominant tRNA binding-dependent arrest of cell growth caused by a reduction in the pool of a specific tRNA. Specific tRNA binding drugs may have therapeutic applications for treatment of microbial pathogens. Images Fig. 1 Fig. 3 PMID:8346197

  3. Fire protection for inactive contaminated structures

    SciTech Connect

    Wyatt, D.M.

    1994-02-01

    In general industry and construction, destruction of an inactive/surplus facility by fire may be considered a blessing. However, in a decommissioned contaminated structure, where radiological and other hazardous materials exist, such a fire could be a major catastrophe. The losses from this type of fire are not only property (i.e., structure and its contents) but also the resulting environmental damage, required cleanup, offsite releases, and public relations and reactions. The purpose of this presentation is to (1) promote an awareness among the waste management community of fire protection engineering aspects that must be considered for inactive/surplus contaminated structures, and (2) present to the fire protection community an opportunity to become involved in the decommissioning process while promoting the DOE objectives to manage the risks associated with these structures.

  4. Exploring human inactivity in computer power consumption

    NASA Astrophysics Data System (ADS)

    Candrawati, Ria; Hashim, Nor Laily Binti

    2016-08-01

    Managing computer power consumption has become an important challenge in computer society and this is consistent with a trend where a computer system is more important to modern life together with a request for increased computing power and functions continuously. Unfortunately, previous approaches are still inadequately designed to handle the power consumption problem due to unpredictable workload of a system caused by unpredictable human behaviors. This is happens due to lack of knowledge in a software system and the software self-adaptation is one approach in dealing with this source of uncertainty. Human inactivity is handled by adapting the behavioral changes of the users. This paper observes human inactivity in the computer usage and finds that computer power usage can be reduced if the idle period can be intelligently sensed from the user activities. This study introduces Control, Learn and Knowledge model that adapts the Monitor, Analyze, Planning, Execute control loop integrates with Q Learning algorithm to learn human inactivity period to minimize the computer power consumption. An experiment to evaluate this model was conducted using three case studies with same activities. The result show that the proposed model obtained those 5 out of 12 activities shows the power decreasing compared to others.

  5. The Global Physical Inactivity Pandemic: An Analysis of Knowledge Production

    ERIC Educational Resources Information Center

    Piggin, Joe; Bairner, Alan

    2016-01-01

    In July 2012, "The Lancet" announced a pandemic of physical inactivity and a global call to action to effect change. The worldwide pandemic is said to be claiming millions of lives every year. Asserting that physical inactivity is pandemic is an important moment. Given the purported scale and significance of physical inactivity around…

  6. AN INACTIVE PRECURSOR OF STREPTOCOCCAL PROTEINASE

    PubMed Central

    Elliott, Stuart D.; Dole, Vincent P.

    1947-01-01

    1. Streptococcal proteinase is derived from an inactive precursor found in culture filtrates of proteinase-producing streptococci. 2. The precursor can be converted into the proteinase by low concentrations of trypsin but not by chymotrypsin. 3. In cultures grown in suitable media the conversion of precursor to proteinase is effected autocatalytically. This reaction occurs under reducing conditions and is initiated by active proteinase present in low concentrations with the precursor. 4. The autocatalytic reaction is suppressed or retarded by conditions which decrease the activity of the proteinase, e.g. by growing cultures at 22°C. instead of at 37°C. or by growing them under markedly aerobic conditions. It is also retarded in the presence of casein. PMID:19871616

  7. Characterizing inactive ribosomes in translational profiling.

    PubMed

    Liu, Botao; Qian, Shu-Bing

    2016-01-01

    The broad impact of translational regulation has emerged explosively in the last few years in part due to the technological advance in genome-wide interrogation of gene expression. During mRNA translation, the majority of actively translating ribosomes exist as polysomes in cells with multiple ribosomes loaded on a single transcript. The importance of the monosome, however, has been less appreciated in translational profiling analysis. Here we report that the monosome fraction isolated by sucrose sedimentation contains a large quantity of inactive ribosomes that do not engage on mRNAs to direct translation. We found that the elongation factor eEF2, but not eEF1A, stably resides in these non-translating ribosomes. This unique feature permits direct evaluation of ribosome status under various stress conditions and in the presence of translation inhibitors. Ribosome profiling reveals that the monosome has a similar but not identical pattern of ribosome footprints compared to the polysome. We show that the association of free ribosomal subunits minimally contributes to ribosome occupancy outside of the coding region. Our results not only offer a quantitative method to monitor ribosome availability, but also uncover additional layers of ribosome status needed to be considered in translational profiling analysis. PMID:27335722

  8. Sarcopenia and Physical Inactivity in Patients With Chronic Kidney Disease.

    PubMed

    Hirai, Keiji; Ookawara, Susumu; Morishita, Yoshiyuki

    2016-05-01

    Sarcopenia and physical inactivity synergistically progress in patients with chronic kidney disease (CKD) and are strong predictors of mortality in this population. Exercise training and essential amino acids and vitamin D supplements may contribute to improving sarcopenia and physical inactivity in CKD patients. PMID:27570755

  9. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  10. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  11. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  12. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT Appeals § 23.63 Appeals from inaction of official. A person or persons whose interests are...

  13. 1. AERIAL VIEW, NAVAL INACTIVE SHIPS MAINTENANCE FACILITY, SINCLAIR ISLET, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. AERIAL VIEW, NAVAL INACTIVE SHIPS MAINTENANCE FACILITY, SINCLAIR ISLET, BREMERTON, KITSAP COUNTY, WASHINGTON WITH EX-USS HORNET CVS-12, THREE MINECRAFT ALONGSIDE TO PORT. OTHER INACTIVE SHIPS IN BACKGROUND. - U.S.S. HORNET, Puget Sound Naval Shipyard, Sinclair Inlet, Bremerton, Kitsap County, WA

  14. An Exploratory Study of Inactive Health Information Seekers

    PubMed Central

    2014-01-01

    Purpose This study aims to identify people who do not actively seek out health information and the demographic characteristics of Inactive Seekers. The possible determinants of inactive seeking behaviors is also explored. Design and Measurements A total of 14,420 survey respondents were drawn from the 2009 Annenberg National Health Communication Survey (ANHCS) data. K-means clustering was used to discriminate Inactive Seekers from Active Seekers. The inactive information seeker group was formed based on their experience with health information seeking. The potential determinants that were tested to predict inactive seeking included the following: health condition, health service use, health media exposure, and computer/Internet activities. Results Within this national survey data, the respondents were more likely to be included in the Inactive Seekers (N=8,312, 58.5%) compared to Active Seekers (N=5,908, 41.5%). The demographic characteristics indicated that the Inactive Seekers were identified as younger, male, highly educated, White, and high household income people. The binary logistic regression results from the study model indicated that healthier people were less likely to seek out health information than their counterparts. In addition, those who were exposed to various media were almost 1.6 times more likely to seek out health information than those who were not exposed to such media. Within this study data, the statistically significant determinants identified were health condition and health media exposure while computer/Internet activities did not show strong indications in predicting inactive seeking behavior. Conclusion The development of more generalizable measures for health literacy or behavioral patterns will bolster advanced study on inactive seeking relating to knowledge of technology and health context. Further study should be directed at estimating the negative aspects of information seeking such as information ignorance or information

  15. Inactive Women May Face Higher Risk for Cervical Cancer

    MedlinePlus

    ... html Inactive Women May Face Higher Risk for Cervical Cancer But study found just 30 minutes of exercise ... who are sedentary appear more likely to develop cervical cancer, but just 30 minutes of exercise each week ...

  16. Dynamics differentiate between active and inactive inteins.

    PubMed

    Cronin, Melissa; Coolbaugh, Michael J; Nellis, David; Zhu, Jianwei; Wood, David W; Nussinov, Ruth; Ma, Buyong

    2015-02-16

    The balance between stability and dynamics for active enzymes can be somewhat quantified by studies of intein splicing and cleaving reactions. Inteins catalyze the ligation of flanking host exteins while excising themselves. The potential for applications led to engineering of a mini-intein splicing domain, where the homing endonuclease domain of the Mycobacterium tuberculosis RecA (Mtu recA) intein was removed. The remaining domains were linked by several short peptides, but splicing activity in all was substantially lower than the full-length intein. Native splicing activity was restored in some cases by a V67L mutation. Using computations and experiments, we examine the impact of this mutation on the stability and conformational dynamics of the mini-intein splicing domain. Molecular dynamics simulations were used to delineate the factors that determine the active state, including the V67L mini-intein mutant, and peptide linker. We found that (1) the V67L mutation lowers the global fluctuations in all modeled mini-inteins, stabilizing the mini-intein constructs; (2) the connecting linker length affects intein dynamics; and (3) the flexibilities of the linker and intein core are higher in the active structure. We have observed that the interaction of the linker region and a turn region around residues 35-41 provides the pathway for the allostery interaction. Our experiments reveal that intein catalysis is characterized by non-linear Arrhenius plot, confirming the significant contribution of protein conformational dynamics to intein function. We conclude that while the V67L mutation stabilizes the global structure, cooperative dynamics of all intein regions appear more important for intein function than high stability. Our studies suggest that effectively quenching the conformational dynamics of an intein through engineered allosteric interactions could deactivate intein splicing or cleaving. PMID:25087201

  17. Association between Physical Inactivity and Academic Record in Korean Adolescents

    PubMed Central

    Shin, Yi-Soo; So, Wi-Young

    2012-01-01

    Background: The purpose of this study was to investigate the association between physical inactivity and academic record in Korean adolescents. Methods: Adolescent students from the first grade of middle school to the third grade of high school (n=75,066) participated in the 5th Korea Youth Risk Behavior Web-based Survey project in 2009. The association between physical inactivity and academic record was assessed using multivariate logistic regression analysis after adjusting for gender, age, body mass index, family’s socioeconomic status, parents’ education level, and frequency of vigorous or moderate physical activity (PA) as well as muscular strength exercises. Results: During weekdays, the odds ratios (ORs) (95% confidence interval [CI]) for reporting a higher than average academic record, as compared with <1 hour of physical inactivity per day, was 0.796 (0.761–0.832, for ≥1 to <2 hours, 0.632 (0.603–0.663, for ≥2 to <3 hours, 0.567 (0.535–0.601, for ≥3 to <4 hours, and 0.494 (0.468–0.522, P < 0.001 for all cases) for ≥4 hours of physical inactivity per day. During the weekends, the ORs (95% CI) for reporting a higher than average academic record, as compared with <1 hour of physical inactivity per day, were 0.901 (0.848–0.957, P = 0.001) for ≥3 to <4 hours and 0.785 (0.743–0.830, P < 0.001) for ≥4 hours of physical inactivity per day. Conclusion: Korean adolescents who spend more time engaged in physical inactivity are predisposed to a below-average academic record. PMID:23308350

  18. Prevalence and factors associated with physical inactivity among Malaysian adults.

    PubMed

    Ying, Chanying; Kuay, Lim Kuang; Huey, Teh Chien; Hock, Lim Kuang; Hamid, Hamizatul Akmal Abd; Omar, Mohd Azahadi; Ahmad, Noor Ani; Cheong, Kee Chee

    2014-03-01

    Using data from the Third National Health and Morbidity Survey (NHMS III) in 2006, this study examined the association between socio-demographic factors and physical inactivity in a sample of 33,949 adults aged 18 years and above by gender. Physical activity levels were measured using the Global Physical Activity Questionnaire (GPAQ vers 1). Physical inactivity was defined as having a total physical activity level of less than 600 metabolic equivalents-minutes per week (METs-minutes/week) contributed by all three different life domains.Logistic regression analyses were conducted.The prevalence of overall physical inactivity was 43.7% (95% CI: 42.9-44.5). The mean total physical activity level was 894.2 METs-minutes/ week. The means METs-minutes/week for the domain of work, travelling, and leisure time were 518.4, 288.1, and 134.8, respectively. Multivariable logistic regression analyses indicated that females were more likely to be physically inactive than males were (aOR=1.62; 95% CI: 1.53-1.72). Among women, being a housewife (aOR = 1.78; 95% CI: 1.56-2.03), widow/divorcee (aOR = 1.23; 95% CI: 1.05-1.43), and those with no formal education (aOR = 1.20; 95% CI: 1.01-1.43) were found to be significantly associated with physical inactivity.Urban residents, older adults aged 65 years and above, private employees, nonworking group, and those with a monthly household income level of MYR5,000 and above appeared to be consistently associated with physical inactivity across men, women, and combined group (both). Specific health intervention strategies to promote physical activity should be targeted on population subgroups who are inactive. PMID:24968689

  19. The Costs of Inaction with Respect to Climate Change

    SciTech Connect

    Cline, William R.

    2005-04-14

    This paper first considers the principal trade-offs in the timing of policy response to climate change. It then turns to a synoptic review of the economic literature on costs and benefits of climate change abatement. The discussion closes with an estimate of the potential economic cost that might be associated with delay in abatement, based on the analysis in the author, published elsewhere. In the specific calculations of the paper, the costs of inaction are specified in two alternative ways. In the first and likely more relevant formulation, it is assumed that inaction persists for only two decades. The costs of inaction are then calculated as the damage arising from the additional climate change above that identified in the optimal abatement path as a consequence of failing to carry out any abatement in the first two decades, net of the savings in abatement costs thereby avoided. In the second and more extreme formulation, inaction is assumed to be permanent (i.e. there is never any reduction in emissions from their baseline path). In this case the costs of inaction are again the net costs of future climate damage after deducting the savings from absence of abatement, but this time over the full time horizon of three centuries.

  20. Parental Predictors of Physical Inactivity in Spanish Adolescents

    PubMed Central

    Sanz-Arazuri, Eva; Ponce-de-León-Elizondo, Ana; Valdemoros-San-Emeterio, María Ángeles

    2012-01-01

    The purpose of this study was to determine some parental predictors of physical inactivity in Spanish adolescents. The sample comprised 1,978 children, aged between 12 and 16 years. A quantitative and qualitative technical triangulation was employed. The study analyzed data of the parents' educational level, the importance they grant to physical-sport activities, and their physical-sport practice. Quantitative technique: a questionnaire (MACOFYD) was used to collect the data. Descriptive, bivariate, and multinomial regression analyses were employed. Statistical significance was set at p < 0.05. Qualitative technique: four discussion groups were conducted, consisting of parents, physical education teachers, teachers of other subjects, and children aged between 12 and 16 years. The results indicated that adolescents are four times more likely to be physically inactive if their parents have never exercised (odds ratio [OR] = 4.065, and = 3.487, for the fathers and mothers, respectively, p < 0.05). When parents grant “some” or “much” importance to physical-sport practice, adolescents are less likely to be physically inactive (OR = 0.185 and 0.118 respectively, p < 0.01). No significant correlation was found between adolescents' physical-sport activity and parents' educational level. However, young people reproach their parents because they emphasize academic goals more than physical-sport practice-an observation that teachers also confirm. Young people perceive their parents as being the education agents with the greatest influence over their inactive lifestyles. Many parents are unaware of their influence and, therefore, do not take responsibility, declaring that the teachers' influence is greater. Key points Parental factors significantly affect adolescent physical inactivity. Parents' physical inactivity is among the most important factors. Statistically significant results were found for gender. Being female tripled the likelihood of being sedentary. The

  1. Inactive conformation enhances binding function in physiological conditions

    PubMed Central

    Yakovenko, Olga; Tchesnokova, Veronika; Sokurenko, Evgeni V.; Thomas, Wendy E.

    2015-01-01

    Many receptors display conformational flexibility, in which the binding pocket has an open inactive conformation in the absence of ligand and a tight active conformation when bound to ligand. Here we study the bacterial adhesin FimH to address the role of the inactive conformation of the pocket for initiating binding by comparing two variants: a wild-type FimH variant that is in the inactive state when not bound to its target mannose, and an engineered activated variant that is always in the active state. Not surprisingly, activated FimH has a longer lifetime and higher affinity, and bacteria expressing activated FimH bound better in static conditions. However, bacteria expressing wild-type FimH bound better in flow. Wild-type and activated FimH demonstrated similar mechanical strength, likely because mechanical force induces the active state in wild-type FimH. However, wild-type FimH displayed a faster bond association rate than activated FimH. Moreover, the ability of different FimH variants to mediate adhesion in flow reflected the fraction of FimH in the inactive state. These results demonstrate a new model for ligand-associated conformational changes that we call the kinetic-selection model, in which ligand-binding selects the faster-binding inactive state and then induces the active state. This model predicts that in physiological conditions for cell adhesion, mechanical force will drive a nonequilibrium cycle that uses the fast binding rate of the inactive state and slow unbinding rate of the active state, for a higher effective affinity than is possible at equilibrium. PMID:26216967

  2. A Rhizobium meliloti mutant that forms ineffective pseudonodules in alfalfa produces exopolysaccharide but fails to form beta-(1----2) glucan.

    PubMed Central

    Geremia, R A; Cavaignac, S; Zorreguieta, A; Toro, N; Olivares, J; Ugalde, R A

    1987-01-01

    A mutant of Rhizobium meliloti that elicited the formation of inactive nodules in alfalfa was found not to form beta-(1----2) glucan in vivo or in vitro. It was nonmotile because it lacks flagella. The 235-kilodalton protein which acts as an intermediate in beta-(1----2) glucan synthesis was undetectable in the mutant. These properties of the mutant are common to those of chvB mutants of Agrobacterium tumefaciens. Exopolysaccharide formation by the R. meliloti mutant was about double that by the wild type. Images PMID:3804979

  3. Identification of inactive medications in narrative medical text.

    PubMed

    Breydo, Eugene M; Chu, Julia T; Turchin, Alexander

    2008-01-01

    Discontinued medications are frequently not removed from EMR medication lists - a patient safety risk. We developed an algorithm to identify inactive medications using in the text of narrative notes in the EMR. The algorithm was evaluated against manual review of 297 randomly selected notes. One in five notes documented inactive medications. Sensitivity and precision of 87.7% and 80.7%, respectively, on per-note basis and 66.3% and 80.0%, respectively, on per-medication basis. When medication names missing from the dictionary were excluded, the algorithm achieved sensitivity of 91.4%. Using real clinical data, the algorithm identified inactive medications documented in the note but still listed as active on the patients medication list in more than one in ten notes. Documentation of inactive medications is common in narrative provider notes and can be computationally extracted. This technology could be employed in real-time patient care as well as for research and quality of care monitoring. PMID:18999079

  4. 25 CFR 23.63 - Appeals from inaction of official.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Appeals from inaction of official. 23.63 Section 23.63 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT... affected, or whose ability to protect such interests is impeded by the failure of an official to act on...

  5. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  6. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid Waste Disposal Programs § 256.25 Recommendation...

  7. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  8. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  9. 40 CFR 256.25 - Recommendation for inactive facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Solid...

  10. Active and inactive faults in southern California viewed from Skylab

    NASA Technical Reports Server (NTRS)

    Merifield, P. M.; Lamar, D. L.

    1975-01-01

    The application is discussed of Skylab imagery along with larger scale photography and field investigations in preparing fault maps of California for use in land use planning. The images were used to assist in distinguishing active from inactive faults (by recognizing indications of recent displacement), determining the length of potentially active faults, identifying previously unmapped faults, and gaining additional information on regional tectonic history.

  11. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  12. C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.

    PubMed

    Kanteti, Rajani; Dhanasingh, Immanuel; El-Hashani, Essam; Riehm, Jacob J; Stricker, Thomas; Nagy, Stanislav; Zaborin, Alexander; Zaborina, Olga; Biron, David; Alverdy, John C; Im, Hae Kyung; Siddiqui, Shahid; Padilla, Pamela A; Salgia, Ravi

    2016-01-01

    We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans. PMID:26574927

  13. 200-Area plateau inactive miscellaneous underground storage tanks locations

    SciTech Connect

    Brevick, C.H.

    1997-12-01

    Fluor Daniel Northwest (FDNW) has been tasked by Lockheed Martin Hanford Corporation (LMHC) to incorporate current location data for 64 of the 200-Area plateau inactive miscellaneous underground storage tanks (IMUST) into the centralized mapping computer database for the Hanford facilities. The IMUST coordinate locations and tank names for the tanks currently assigned to the Hanford Site contractors are listed in Appendix A. The IMUST are inactive tanks installed in underground vaults or buried directly in the ground within the 200-East and 200-West Areas of the Hanford Site. The tanks are categorized as tanks with a capacity of less than 190,000 liters (50,000 gal). Some of the IMUST have been stabilized, pumped dry, filled with grout, or may contain an inventory or radioactive and/or hazardous materials. The IMUST have been out of service for at least 12 years.

  14. Investigation of the organic matter in inactive nuclear tank liquids

    SciTech Connect

    Schenley, R.L.; Griest, W.H.

    1990-08-01

    Environmental Protection Agency (EPA) methodology for regulatory organics fails to account for the organic matter that is suggested by total organic carbon (TOC) analysis in the Oak Ridge National Laboratory (ORNL) inactive nuclear waste-tank liquids and sludges. Identification and measurement of the total organics are needed to select appropriate waste treatment technologies. An initial investigation was made of the nature of the organics in several waste-tank liquids. This report details the analysis of ORNL wastes.

  15. Physical inactivity: the "Cinderella" risk factor for noncommunicable disease prevention.

    PubMed

    Bull, Fiona C; Bauman, Adrian E

    2011-08-01

    There is strong evidence demonstrating the direct and indirect pathways by which physical activity prevents many of the major noncommunicable diseases (NCD) responsible for premature death and disability. Physical inactivity was identified as the 4th leading risk factor for the prevention of NCD, preceded only by tobacco use, hypertension, and high blood glucose levels, and accounting for more than 3 million preventable deaths globally in 2010. Physical inactivity is a global public health priority but, in most countries, this has not yet resulted in widespread recognition nor specific physical activity-related policy action at the necessary scale. Instead, physical inactivity could be described as the Cinderella of NCD risk factors, defined as "poverty of policy attention and resourcing proportionate to its importance." The pressing question is "Why is this so?" The authors identify and discuss 8 possible explanations and the need for more effective communication on the importance of physical activity in the NCD prevention context. Although not all of the issues identified will be relevant for any 1 country, it is likely that at different times and in different combinations these 8 problems continue to delay national-level progress on addressing physical inactivity in many countries. The authors confirm that there is sufficient evidence to act, and that much better use of well-planned, coherent communication strategies are needed in most countries and at the international level. Significant opportunities exist. The Toronto Charter on Physical Activity and the Seven Investments that Work are 2 useful tools to support increased advocacy on physical activity within and beyond the context of the crucial 2011 UN High-Level Meeting on NCDs. PMID:21916710

  16. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  17. Connexin Mutants and Cataracts

    PubMed Central

    Beyer, Eric C.; Ebihara, Lisa; Berthoud, Viviana M.

    2013-01-01

    The lens is a multicellular, but avascular tissue that must stay transparent to allow normal transmission of light and focusing of it on the retina. Damage to lens cells and/or proteins can cause cataracts, opacities that disrupt these processes. The normal survival of the lens is facilitated by an extensive network of gap junctions formed predominantly of connexin46 and connexin50. Mutations of the genes that encode these connexins (GJA3 and GJA8) have been identified and linked to inheritance of cataracts in human families and mouse lines. In vitro expression studies of several of these mutants have shown that they exhibit abnormalities that may lead to disease. Many of the mutants reduce or modify intercellular communication due to channel alterations (including loss of function or altered gating) or due to impaired cellular trafficking which reduces the number of gap junction channels within the plasma membrane. However, the abnormalities detected in studies of other mutants suggest that they cause cataracts through other mechanisms including gain of hemichannel function (leading to cell injury and death) and formation of cytoplasmic accumulations (that may act as light scattering particles). These observations and the anticipated results of ongoing studies should elucidate the mechanisms of cataract development due to mutations of lens connexins and abnormalities of other lens proteins. They may also contribute to our understanding of the mechanisms of disease due to connexin mutations in other tissues. PMID:23596416

  18. ERICA: leisure-time physical inactivity in Brazilian adolescents.

    PubMed

    Cureau, Felipe Vogt; Silva, Thiago Luiz Nogueira da; Bloch, Katia Vergetti; Fujimori, Elizabeth; Belfort, Dilson Rodrigues; Carvalho, Kênia Mara Baiocchi de; Leon, Elisa Brosina de; Vasconcellos, Mauricio Teixeira Leite de; Ekelund, Ulf; Schaan, Beatriz D

    2016-02-01

    OBJECTIVE To evaluate the prevalence of leisure-time physical inactivity in Brazilian adolescents and their association with geographical and sociodemographic variables. METHODS The sample was composed by 74,589 adolescents participating in the Study of Cardiovascular Risks in Adolescents (ERICA). This cross-sectional study of school basis with national scope involved adolescents aged from 12 to 17 years in Brazilian cities with more than 100 thousand inhabitants. The prevalence of leisure-time physical inactivity was categorized according to the volume of weekly practice (< 300; 0 min). The prevalences were estimated for the total sample and by sex. Poisson regression models were used to assess associated factors. RESULTS The prevalence of leisure-time physical inactivity was 54.3% (95%CI 53.4-55.2), and higher for the female sex (70.7%, 95%CI 69.5-71.9) compared to the male (38.0%, 95%CI 36.7-39.4). More than a quarter of adolescents (26.5%, 95%CI 25.8-27.3) reported not practicing physical activity in the leisure time, a condition more prevalent for girls (39.8%, 95%CI 38.8-40.9) than boys (13.4%, 95%CI 12.4-14.4). For girls, the variables that were associated with physical inactivity were: reside in the Northeast (RP = 1.13, 95%CI 1.08-1.19), Southeast (RP = 1.16, 95%CI 1.11-1.22) and South (RP = 1.12, 95%CI 1.06-1.18); have 16-17 years (RP = 1.06, 95%CI 1.12-1.15); and belong to the lower economic class (RP = 1.33, 95%CI 1.20-1.48). The same factors, except reside in the Southeast and South, were also associated with not practicing physical activity in the leisure time for the same group. In males, as well as the region, being older (p < 0.001) and declaring to be indigenous (RP = 0.37, 95%CI 0.19-0.73) were also associated with not practicing physical activities in the leisure time. CONCLUSIONS The prevalence of leisure-time physical inactivity in Brazilian adolescents is high. It presents regional variations and is associated with age and low socioeconomic

  19. ERICA: leisure-time physical inactivity in Brazilian adolescents

    PubMed Central

    Cureau, Felipe Vogt; da Silva, Thiago Luiz Nogueira; Bloch, Katia Vergetti; Fujimori, Elizabeth; Belfort, Dilson Rodrigues; de Carvalho, Kênia Mara Baiocchi; de Leon, Elisa Brosina; de Vasconcellos, Mauricio Teixeira Leite; Ekelund, Ulf; Schaan, Beatriz D

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate the prevalence of leisure-time physical inactivity in Brazilian adolescents and their association with geographical and sociodemographic variables. METHODS The sample was composed by 74,589 adolescents participating in the Study of Cardiovascular Risks in Adolescents (ERICA). This cross-sectional study of school basis with national scope involved adolescents aged from 12 to 17 years in Brazilian cities with more than 100 thousand inhabitants. The prevalence of leisure-time physical inactivity was categorized according to the volume of weekly practice (< 300; 0 min). The prevalences were estimated for the total sample and by sex. Poisson regression models were used to assess associated factors. RESULTS The prevalence of leisure-time physical inactivity was 54.3% (95%CI 53.4-55.2), and higher for the female sex (70.7%, 95%CI 69.5-71.9) compared to the male (38.0%, 95%CI 36.7-39.4). More than a quarter of adolescents (26.5%, 95%CI 25.8-27.3) reported not practicing physical activity in the leisure time, a condition more prevalent for girls (39.8%, 95%CI 38.8-40.9) than boys (13.4%, 95%CI 12.4-14.4). For girls, the variables that were associated with physical inactivity were: reside in the Northeast (RP = 1.13, 95%CI 1.08-1.19), Southeast (RP = 1.16, 95%CI 1.11-1.22) and South (RP = 1.12, 95%CI 1.06-1.18); have 16-17 years (RP = 1.06, 95%CI 1.12-1.15); and belong to the lower economic class (RP = 1.33, 95%CI 1.20-1.48). The same factors, except reside in the Southeast and South, were also associated with not practicing physical activity in the leisure time for the same group. In males, as well as the region, being older (p < 0.001) and declaring to be indigenous (RP = 0.37, 95%CI 0.19-0.73) were also associated with not practicing physical activities in the leisure time. CONCLUSIONS The prevalence of leisure-time physical inactivity in Brazilian adolescents is high. It presents regional variations and is associated with age and low

  20. 37 CFR 11.19 - Disciplinary jurisdiction; Jurisdiction to transfer to disability inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...; Jurisdiction to transfer to disability inactive status. 11.19 Section 11.19 Patents, Trademarks, and Copyrights... disability inactive status. (a) All practitioners engaged in practice before the Office; all practitioners... transferred to disability inactive status, reprimanded, suspended, or excluded from the practice of law by...

  1. 37 CFR 11.29 - Reciprocal transfer or initial transfer to disability inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... initial transfer to disability inactive status. 11.29 Section 11.29 Patents, Trademarks, and Copyrights..., Sanctions, Investigations, and Proceedings § 11.29 Reciprocal transfer or initial transfer to disability inactive status. (a) Notification of OED Director. (1) Transfer to disability inactive status in...

  2. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types... circumstances. (c) Transfer to disability inactive status. The USPTO Director, after notice and opportunity...

  3. Molecular basis for the catalytic inactivity of a naturally occurring near-null variant of human ALOX15.

    PubMed

    Horn, Thomas; Ivanov, Igor; Di Venere, Almerinda; Kakularam, Kumar Reddy; Reddanna, Pallu; Conrad, Melanie L; Richter, Constanze; Scheerer, Patrick; Kuhn, Hartmut

    2013-12-01

    Mammalian lipoxygenases belong to a family of lipid-peroxidizing enzymes, which have been implicated in cardiovascular, hyperproliferative and neurodegenerative diseases. Here we report that a naturally occurring mutation in the hALOX15 gene leads to expression of a catalytically near-null enzyme variant (hGly422Glu). The inactivity may be related to severe misfolding of the enzyme protein, which was concluded from CD-spectra as well as from thermal and chemical stability assays. In silico mutagenesis experiments suggest that most mutations at hGly422 have the potential to induce sterical clash, which might be considered a reason for protein misfolding. hGly422 is conserved among ALOX5, ALOX12 and ALOX15 isoforms and corresponding hALOX12 and hALOX5 mutants also exhibited a reduced catalytic activity. Interestingly, in the hALOX5 Gly429Glu mutants the reaction specificity of arachidonic acid oxygenation was shifted from 5S- to 8S- and 12R-H(p)ETE formation. Taken together, our data indicate that the conserved glycine is of functional importance for these enzyme variants and most mutants at this position lose catalytic activity. PMID:23958500

  4. Xist Exon 7 Contributes to the Stable Localization of Xist RNA on the Inactive X-Chromosome

    PubMed Central

    Yamada, Norishige; Hasegawa, Yuko; Yue, Minghui; Hamada, Tomofumi; Nakagawa, Shinichi; Ogawa, Yuya

    2015-01-01

    To equalize X-linked gene dosage between the sexes in mammalian females, Xist RNA inactivates one of the two X-chromosomes. Here, we report the crucial function of Xist exon 7 in X-inactivation. Xist exon 7 is the second-largest exon with a well-conserved repeat E in eutherian mammals, but its role is often overlooked in X-inactivation. Although female ES cells with a targeted truncation of the Xist exon 7 showed no significant differences in their Xist expression levels and RNA stability from control cells expressing wild-type Xist, compromised localization of Xist RNA and incomplete silencing of X-linked genes on the inactive X-chromosome (Xi) were observed in the exon 7-truncated mutant cells. Furthermore, the interaction between the mutant Xist RNA and hnRNP U required for localization of Xist RNA to the Xi was impaired in the Xist exon 7 truncation mutant cells. Our results suggest that exon 7 of Xist RNA plays an important role for stable Xist RNA localization and silencing of the X-linked genes on the Xi, possibly acting through an interaction with hnRNP U. PMID:26244333

  5. The zebrafish early arrest mutants.

    PubMed

    Kane, D A; Maischein, H M; Brand, M; van Eeden, F J; Furutani-Seiki, M; Granato, M; Haffter, P; Hammerschmidt, M; Heisenberg, C P; Jiang, Y J; Kelsh, R N; Mullins, M C; Odenthal, J; Warga, R M; Nüsslein-Volhard, C

    1996-12-01

    This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes. PMID:9007229

  6. Physical inactivity in COPD and increased patient perception of dyspnea

    PubMed Central

    Katajisto, Milla; Kupiainen, Henna; Rantanen, Piritta; Lindqvist, Ari; Kilpeläinen, Maritta; Tikkanen, Heikki; Laitinen, Tarja

    2012-01-01

    Objective: To study patients’ levels of exercise activity and the clinical characteristics that relate to physical activity and inactivity among patients with chronic obstructive pulmonary disease (COPD). Methods: A postal questionnaire was administered to 719 patients with COPD in 2010; patients were recruited from the Helsinki and Turku University Central Hospitals in Finland and have been followed since 2005. The questionnaire asked participants about their exercise routines and other daily activities, potential restrictions to exercise, health-related quality of life, and subjective sensations of dyspnea upon exertion. Results: A total of 50% of the participants reported exercising > 2 times a week throughout the year. The proportion of the exercise inactive patients increased in parallel with disease progression, but the participants exhibited great variation in the degree of activity as well as in sport choices. Year-round activity was better maintained among patients who exercised both indoors and outdoors. Training activity was significantly correlated with patients’ reported subjective dyspnea (r = 0.32, P < 0.001), health-related quality of life (r = 0.25, P < 0.001), mobility score (r = 0.37, P < 0.001), and bronchial obstruction (r = 0.18, P < 0.001). Active patients did not differ from inactive patients in terms of sex, age, smoking status, somatic comorbidities, or body mass index. Irrespective of the level of severity of patients’ COPD, the most significant barrier to exercising was the subjective sensation of dyspnea. Conclusion: When a patient with COPD suffers from dyspnea and does not have regular exercise routines, the patient will most likely benefit from an exercise program tailored to his or her physical capabilities. PMID:23152679

  7. Inactive mutants of human pyridoxine 5'-phosphate oxidase: a possible role for a noncatalytic pyridoxal 5'-phosphate tight binding site.

    PubMed

    Ghatge, Mohini S; Karve, Sayali S; David, Tanya M S; Ahmed, Mostafa H; Musayev, Faik N; Cunningham, Kendra; Schirch, Verne; Safo, Martin K

    2016-05-01

    Pyridoxal 5'-phosphate (PLP) is a cofactor for many vitamin B6-requiring enzymes that are important for the synthesis of neurotransmitters. Pyridoxine 5'-phosphate oxidase (PNPO) is one of two enzymes that produce PLP. Some 16 known mutations in human PNPO (hPNPO), including R95C and R229W, lead to deficiency of PLP in the cell and have been shown to cause neonatal epileptic encephalopathy (NEE). This disorder has no effective treatment, and is often fatal unless treated with PLP. In this study, we show that R95C hPNPO exhibits a 15-fold reduction in affinity for the FMN cofactor, a 71-fold decrease in affinity for the substrate PNP, a 4.9-fold decrease in specific activity, and a 343-fold reduction in catalytic activity, compared to the wild-type enzyme. We have reported similar findings for R229W hPNPO. This report also shows that wild-type, R95C and R229W hPNPO bind PLP tightly at a noncatalytic site and transfer it to activate an apo-B6 enzyme into the catalytically active holo-form. We also show for the first time that hPNPO forms specific interactions with several B6 enzymes with dissociation constants ranging from 0.3 to 12.3 μm. Our results suggest a possible in vivo role for the tight binding of PLP in hPNPO, whether wild-type or variant, by protecting the very reactive PLP, and transferring this PLP directly to activate apo-B6 enzymes. PMID:27419045

  8. Alterations in protein metabolism during space flight and inactivity.

    PubMed

    Ferrando, Arny A; Paddon-Jones, Doug; Wolfe, Robert R

    2002-10-01

    Space flight and the accompanying diminished muscular activity lead to a loss of body nitrogen and muscle function. These losses may affect crew capabilities and health in long-duration missions. Space flight alters protein metabolism such that the body is unable to maintain protein synthetic rates. A concomitant hypocaloric intake and altered anabolic/catabolic hormonal profiles may contribute to or exacerbate this problem. The inactivity associated with bedrest also reduces muscle and whole-body protein synthesis. For this reason, bedrest provides a good model for the investigation of potential exercise and nutritional countermeasures to restore muscle protein synthesis. We have demonstrated that minimal resistance exercise preserves muscle protein synthesis throughout bedrest. In addition, ongoing work indicates that an essential amino acid and carbohydrate supplement may ameliorate the loss of lean body mass and muscle strength associated with 28 d of bedrest. The investigation of inactivity-induced alterations in protein metabolism, during space flight or prolonged bedrest, is applicable to clinical populations and, in a more general sense, to the problems associated with the decreased activity that occur with aging. PMID:12361775

  9. Enzyme Inhibition by Allosteric Capture of an Inactive Conformation

    PubMed Central

    Lee, Gregory M.; Shahian, Tina; Baharuddin, Aida; Gable, Jonathan E.; Craik, Charles S.

    2011-01-01

    All members of the human herpesvirus protease family are active as weakly associating dimers, but inactive as monomers. A small molecule allosteric inhibitor of Kaposi’s sarcoma-associated herpesvirus protease (KSHV Pr) traps the enzyme in an inactive monomeric state where the C-terminal helices are unfolded and the hydrophobic dimer interface is exposed. NMR titration studies demonstrate that the inhibitor binds to KSHV Pr monomers with low μM affinity. A 2.0 Å resolution X-ray crystal structure of a C-terminal truncated KSHV Pr-inhibitor complex locates the binding pocket at the dimer interface and displays significant conformational perturbations at the active site, 15 Å from the allosteric site. NMR and CD data suggest that the small molecule inhibits human cytomegalovirus protease (HCMV Pr) via a similar mechanism. As all HHV proteases are functionally and structurally homologous, the inhibitor represents a class of compounds that may be developed into broad-spectrum therapeutics which allosterically regulate enzymatic activity by disrupting protein-protein interactions. PMID:21723875

  10. Alterations in protein metabolism during space flight and inactivity

    NASA Technical Reports Server (NTRS)

    Ferrando, Arny A.; Paddon-Jones, Doug; Wolfe, Robert R.

    2002-01-01

    Space flight and the accompanying diminished muscular activity lead to a loss of body nitrogen and muscle function. These losses may affect crew capabilities and health in long-duration missions. Space flight alters protein metabolism such that the body is unable to maintain protein synthetic rates. A concomitant hypocaloric intake and altered anabolic/catabolic hormonal profiles may contribute to or exacerbate this problem. The inactivity associated with bedrest also reduces muscle and whole-body protein synthesis. For this reason, bedrest provides a good model for the investigation of potential exercise and nutritional countermeasures to restore muscle protein synthesis. We have demonstrated that minimal resistance exercise preserves muscle protein synthesis throughout bedrest. In addition, ongoing work indicates that an essential amino acid and carbohydrate supplement may ameliorate the loss of lean body mass and muscle strength associated with 28 d of bedrest. The investigation of inactivity-induced alterations in protein metabolism, during space flight or prolonged bedrest, is applicable to clinical populations and, in a more general sense, to the problems associated with the decreased activity that occur with aging.

  11. Physical Inactivity and Incidence of Obesity among South Australian Adults

    PubMed Central

    Montgomerie, Alicia M.; Chittleborough, Catherine R.; Taylor, Anne W.

    2014-01-01

    The aim of this paper is to examine the association of physical inactivity with incidence of obesity in the South Australian adult population. Two representative data sources were used – the South Australian Monitoring and Surveillance System (SAMSS), a monthly surveillance system, and the North West Adelaide Health Study (NWAHS), a biomedical cohort study. There were 75.3% (n = 12873) SAMSS participants and 72.8% (n = 1521) of NWAHS participants that were not obese at baseline. The cumulative incidence of obesity for SAMSS participants from the previous year to the current year was 2.7%. The cumulative incidence of obesity for NWAHS participants between baseline and stage 3 was 14.4%. Physical inactivity was associated with incident obesity (RR 1.48, 95% CI 1.14–1.90 [SAMSS] and RR 1.41, 95% CI 1.03–1.93 [NWAHS]). This association remained, but was attenuated after adjustment for chronic conditions, risk factors and socio-demographic factors. However, physical activity should be continued to be encouraged in the population for its known additional health benefits. PMID:25383626

  12. ECB deacylase mutants

    DOEpatents

    Arnold, Frances H.; Shao, Zhixin; Zhao, Huimin; Giver, Lorraine J.

    2002-01-01

    A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

  13. Human development, occupational structure and physical inactivity among 47 low and middle income countries

    PubMed Central

    Atkinson, Kaitlin; Lowe, Samantha; Moore, Spencer

    2015-01-01

    This study aimed to (a) assess the relationship between a person's occupational category and their physical inactivity, and (b) analyze the association among country-level variables and physical inactivity. The World Health Survey (WHS) was administered in 2002–2003 among 47 low- and middle-income countries (n = 196,742). The International Physical Activity Questionnaire (IPAQ) was used to collect verbal reports of physical activity and convert responses into measures of physical inactivity. Economic development (GDP/c), degree of urbanization, and the Human Development Index (HDI) were used to measure country-level variables and physical inactivity. Multilevel logistic regression analysis was used to examine the association among country-level factors, individual occupational status, and physical inactivity. Overall, the worldwide prevalence of physical inactivity in 2002–2003 was 23.7%. Individuals working in the white-collar industry compared to agriculture were 84% more likely to be physically inactive (OR: 1.84, CI: 1.73–1.95). Among low- and middle-income countries increased HDI values were associated with decreased levels of physical inactivity (OR: 0.98, CI: 0.97–0.99). This study is one of the first to adjust for within-country differences, specifically occupation while analyzing physical inactivity. As countries experience economic development, changes are also seen in their occupational structure, which result in increased countrywide physical inactivity levels. PMID:26844185

  14. Human development, occupational structure and physical inactivity among 47 low and middle income countries.

    PubMed

    Atkinson, Kaitlin; Lowe, Samantha; Moore, Spencer

    2016-06-01

    This study aimed to (a) assess the relationship between a person's occupational category and their physical inactivity, and (b) analyze the association among country-level variables and physical inactivity. The World Health Survey (WHS) was administered in 2002-2003 among 47 low- and middle-income countries (n = 196,742). The International Physical Activity Questionnaire (IPAQ) was used to collect verbal reports of physical activity and convert responses into measures of physical inactivity. Economic development (GDP/c), degree of urbanization, and the Human Development Index (HDI) were used to measure country-level variables and physical inactivity. Multilevel logistic regression analysis was used to examine the association among country-level factors, individual occupational status, and physical inactivity. Overall, the worldwide prevalence of physical inactivity in 2002-2003 was 23.7%. Individuals working in the white-collar industry compared to agriculture were 84% more likely to be physically inactive (OR: 1.84, CI: 1.73-1.95). Among low- and middle-income countries increased HDI values were associated with decreased levels of physical inactivity (OR: 0.98, CI: 0.97-0.99). This study is one of the first to adjust for within-country differences, specifically occupation while analyzing physical inactivity. As countries experience economic development, changes are also seen in their occupational structure, which result in increased countrywide physical inactivity levels. PMID:26844185

  15. Tyrosyl-DNA phosphodiesterase I catalytic mutants reveal an alternative nucleophile that can catalyze substrate cleavage.

    PubMed

    Comeaux, Evan Q; Cuya, Selma M; Kojima, Kyoko; Jafari, Nauzanene; Wanzeck, Keith C; Mobley, James A; Bjornsti, Mary-Ann; van Waardenburg, Robert C A M

    2015-03-01

    Tyrosyl-DNA phosphodiesterase I (Tdp1) catalyzes the repair of 3'-DNA adducts, such as the 3'-phosphotyrosyl linkage of DNA topoisomerase I to DNA. Tdp1 contains two conserved catalytic histidines: a nucleophilic His (His(nuc)) that attacks DNA adducts to form a covalent 3'-phosphohistidyl intermediate and a general acid/base His (His(gab)), which resolves the Tdp1-DNA linkage. A His(nuc) to Ala mutant protein is reportedly inactive, whereas the autosomal recessive neurodegenerative disease SCAN1 has been attributed to the enhanced stability of the Tdp1-DNA intermediate induced by mutation of His(gab) to Arg. However, here we report that expression of the yeast His(nuc)Ala (H182A) mutant actually induced topoisomerase I-dependent cytotoxicity and further enhanced the cytotoxicity of Tdp1 His(gab) mutants, including H432N and the SCAN1-related H432R. Moreover, the His(nuc)Ala mutant was catalytically active in vitro, albeit at levels 85-fold less than that observed with wild type Tdp1. In contrast, the His(nuc)Phe mutant was catalytically inactive and suppressed His(gab) mutant-induced toxicity. These data suggest that the activity of another nucleophile when His(nuc) is replaced with residues containing a small side chain (Ala, Asn, and Gln), but not with a bulky side chain. Indeed, genetic, biochemical, and mass spectrometry analyses show that a highly conserved His, immediately N-terminal to His(nuc), can act as a nucleophile to catalyze the formation of a covalent Tdp1-DNA intermediate. These findings suggest that the flexibility of Tdp1 active site residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl intermediates and provide the rationale for developing chemotherapeutics that stabilize the covalent Tdp1-DNA intermediate. PMID:25609251

  16. Mechanical properties and fiber type composition of chronically inactive muscles

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Zhong, H.; Monti, R. J.; Vallance, K. A.; Kim, J. A.; Edgerton, V. R.

    2000-01-01

    A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties.

  17. Prevalence of atherosclerosis in patients with inactive rheumatoid arthritis.

    PubMed

    Dehghan, Pooneh; Rajaei, Alireza; Moeineddin, Reza; Alizadeh, Afshin Mohammad

    2015-08-01

    Patients with rheumatoid arthritis (RA) exhibit higher cardiovascular morbidity and mortality than the general population. The common carotid artery intima-media thickness (CCA-IMT) measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in patients with inactive RA. CCA-IMT was measured at the level of the carotid bifurcation in 35 patients with RA and 35 age- and sex-matched controls. CCA-IMT measurements more than two standard deviations above the mean measurement of the control group were defined as abnormal. Patients and controls with known cardiovascular risk factors were excluded from the study. The following data were taken into consideration for each patient: age, sex, duration of RA, and medication received by the patient. These variables were adjusted in data analysis. The patients were required to have had normal C-reactive protein levels for at least 1 year and no clinical signs or symptoms of active disease. An independent t test and chi-squared test were used for statistical analysis. Nine patients with RA (25.7 %) and two controls (5.7 %) had an abnormal IMT. Patients showed more carotid atherosclerotic plaques and a higher mean CCA-IMT than did controls (48.6 vs. 14.3 % and 0.705 ± 0.140 vs. 0.580 ± 0.125, respectively). An abnormal CCA-IMT was more prevalent in patients >50 years of age with >5 years of involvement (P = 0.001). These results support the theory that chronic inflammation in patients with inactive RA is associated with atherosclerosis and suggest the use of carotid ultrasonography as a useful tool with which to establish the risk of cardiovascular disease. PMID:26122966

  18. KEPLER FLARES. I. ACTIVE AND INACTIVE M DWARFS

    SciTech Connect

    Hawley, Suzanne L.; Davenport, James R. A.; Kowalski, Adam F.; Wisniewski, John P.; Deitrick, Russell; Hilton, Eric J.; Hebb, Leslie

    2014-12-20

    We analyzed Kepler short-cadence M dwarf observations. Spectra from the Astrophysical Research Consortium 3.5 m telescope identify magnetically active (Hα in emission) stars. The active stars are of mid-M spectral type, have numerous flares, and have well-defined rotational modulation due to starspots. The inactive stars are of early M type, exhibit less starspot signature, and have fewer flares. A Kepler to U-band energy scaling allows comparison of the Kepler flare frequency distributions with previous ground-based data. M dwarfs span a large range of flare frequency and energy, blurring the distinction between active and inactive stars designated solely by the presence of Hα. We analyzed classical and complex (multiple peak) flares on GJ 1243, finding strong correlations between flare energy, amplitude, duration, and decay time, with only a weak dependence on rise time. Complex flares last longer and have higher energy at the same amplitude, and higher energy flares are more likely to be complex. A power law fits the energy distribution for flares with log E{sub K{sub p}}> 31 erg, but the predicted number of low-energy flares far exceeds the number observed, at energies where flares are still easily detectable, indicating that the power-law distribution may flatten at low energy. There is no correlation of flare occurrence or energy with starspot phase, the flare waiting time distribution is consistent with flares occurring randomly in time, and the energies of consecutive flares are uncorrelated. These observations support a scenario where many independent active regions on the stellar surface are contributing to the observed flare rate.

  19. Nutritional status and physical inactivity in moderated asthmatics

    PubMed Central

    Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

    2016-01-01

    Abstract Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity. Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants. FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12). This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening. PMID:27495092

  20. Naïve Definitions of Action and Inaction: The Continuum, Spread, and Valence of Behaviors

    PubMed Central

    McCulloch, Kathleen C.; Li, Hong; Hong, Sungjin; Albarracin, Dolores

    2011-01-01

    The cohesiveness of a society depends, in part, on how its individual members manage their daily activities with respect to the goals of that society. Hence, there should be a degree of social agreement on what constitutes action and what constitutes inaction. The present research investigated the structure of action and inaction definitions, the evaluation of action versus inaction, and individual differences in these evaluations. Action-inaction ratings of behaviors and states showed more social agreement at the ends of the inaction-action continuum than at the middle, suggesting a socially shared construal of this definition. Action-inaction ratings were also shown to correlate with the valence of the rated behaviors, such that the more active the behavior the more positive its valence. Lastly, individual differences in locomotion, need for closure, and Christian religious beliefs correlated positively with a preference for action. PMID:23487013

  1. Calculating a checksum with inactive networking components in a computing system

    DOEpatents

    Aho, Michael E; Chen, Dong; Eisley, Noel A; Gooding, Thomas M; Heidelberger, Philip; Tauferner, Andrew T

    2015-01-27

    Calculating a checksum utilizing inactive networking components in a computing system, including: identifying, by a checksum distribution manager, an inactive networking component, wherein the inactive networking component includes a checksum calculation engine for computing a checksum; sending, to the inactive networking component by the checksum distribution manager, metadata describing a block of data to be transmitted by an active networking component; calculating, by the inactive networking component, a checksum for the block of data; transmitting, to the checksum distribution manager from the inactive networking component, the checksum for the block of data; and sending, by the active networking component, a data communications message that includes the block of data and the checksum for the block of data.

  2. Calculating a checksum with inactive networking components in a computing system

    DOEpatents

    Aho, Michael E; Chen, Dong; Eisley, Noel A; Gooding, Thomas M; Heidelberger, Philip; Tauferner, Andrew T

    2014-12-16

    Calculating a checksum utilizing inactive networking components in a computing system, including: identifying, by a checksum distribution manager, an inactive networking component, wherein the inactive networking component includes a checksum calculation engine for computing a checksum; sending, to the inactive networking component by the checksum distribution manager, metadata describing a block of data to be transmitted by an active networking component; calculating, by the inactive networking component, a checksum for the block of data; transmitting, to the checksum distribution manager from the inactive networking component, the checksum for the block of data; and sending, by the active networking component, a data communications message that includes the block of data and the checksum for the block of data.

  3. Biologically inactive leptin and early-onset extreme obesity.

    PubMed

    Wabitsch, Martin; Funcke, Jan-Bernd; Lennerz, Belinda; Kuhnle-Krahl, Ursula; Lahr, Georgia; Debatin, Klaus-Michael; Vatter, Petra; Gierschik, Peter; Moepps, Barbara; Fischer-Posovszky, Pamela

    2015-01-01

    Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss. PMID:25551525

  4. Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1.

    PubMed

    Sampath, J; Sun, D; Kidd, V J; Grenet, J; Gandhi, A; Shapiro, L H; Wang, Q; Zambetti, G P; Schuetz, J D

    2001-10-19

    The most frequently expressed drug resistance genes, MDR1 and MRP1, occur in human tumors with mutant p53. However, it was unknown if mutant p53 transcriptionally regulated both MDR1 and MRP1. We demonstrated that mutant p53 did not activate either the MRP1 promoter or the endogenous gene. In contrast, mutant p53 strongly up-regulated the MDR1 promoter and expression of the endogenous MDR1 gene. Notably, cells that expressed either a transcriptionally inactive mutant p53 or the empty vector showed no endogenous MDR1 up-regulation. Transcriptional activation of the MDR1 promoter by mutant p53 required an Ets binding site, and mutant p53 and Ets-1 synergistically activated MDR1 transcription. Biochemical analysis revealed that Ets-1 interacted exclusively with mutant p53s in vivo but not with wild-type p53. These findings are the first to demonstrate the induction of endogenous MDR1 by mutant p53 and provide insight into the mechanism. PMID:11483599

  5. Reexamination of alcohol dehydrogenase structural mutants in Drosophila using protein blotting

    SciTech Connect

    Hollocher, H.; Place, A.R.

    1987-06-01

    Using protein blotting and an immuno-overlay procedure, the authors have reexamined the cross-reacting material produced by ADH null-activity mutants generated with ethyl methanesulfonate (EMS). Of the 13 mutants, 11 have an immunodetectable polypeptide of wild-type size. The native and urea denatured isoelectric points (pI) establish that 7 of 13 of the mutations have no effect on protein charge. The electrophoretic mobilities of each variant on increasing percent acrylamide gels (Ferguson analysis), reveal that 9 of the 11 immunodetectable mutations have retained the ability form dimers under native conditions. None of the inactive mutant proteins has the ability to form the adduct-bound isozyme. The authors have found no correlation between protein pI and i vivo stability. The observed frequencies of specific charge class alterations do not dispute the propensity of G:A transitions previously found for EMS mutagenesis.

  6. Burden of physical inactivity and hospitalization costs due to chronic diseases

    PubMed Central

    Bielemann, Renata Moraes; da Silva, Bruna Gonçalves Cordeiro; Coll, Carolina de Vargas Nunes; Xavier, Mariana Otero; da Silva, Shana Ginar

    2015-01-01

    OBJECTIVE To evaluate the physical inactivity-related inpatient costs of chronic non-communicable diseases. METHODS This study used data from 2013, from Brazilian Unified Health System, regarding inpatient numbers and costs due to malignant colon and breast neoplasms, cerebrovascular diseases, ischemic heart diseases, hypertension, diabetes, and osteoporosis. In order to calculate the share physical inactivity represents in that, the physical inactivity-related risks, which apply to each disease, were considered, and physical inactivity prevalence during leisure activities was obtained from Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey). The analysis was stratified by genders and residing country regions of subjects who were 40 years or older. The physical inactivity-related hospitalization cost regarding each cause was multiplied by the respective share it regarded to. RESULTS In 2013, 974,641 patients were admitted due to seven different causes in Brazil, which represented a high cost. South region was found to have the highest patient admission rate in most studied causes. The highest prevalences for physical inactivity were observed in North and Northeast regions. The highest inactivity-related share in men was found for osteoporosis in all regions (≈ 35.0%), whereas diabetes was found to have a higher share regarding inactivity in women (33.0% to 37.0% variation in the regions). Ischemic heart diseases accounted for the highest total costs that could be linked to physical inactivity in all regions and for both genders, being followed by cerebrovascular diseases. Approximately 15.0% of inpatient costs from Brazilian Unified Health System were connected to physical inactivity. CONCLUSIONS Physical inactivity significantly impacts the number of patient admissions due to the evaluated causes and through their resulting costs, with different genders and country regions representing different shares. PMID:26487291

  7. Structural organization of the inactive X chromosome in the mouse.

    PubMed

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  8. Nonchemotactic Mutants of Escherichia coli

    PubMed Central

    Armstrong, John B.; Adler, Julius; Dahl, Margaret M.

    1967-01-01

    We have isolated 40 mutants of Escherichia coli which are nonchemotactic as judged by their failure to swarm on semisolid tryptone plates or to make bands in capillary tubes containing tryptone broth. All the mutants have normal flagella, a fact shown by their shape and reaction with antiflagella serum. All are fully motile under the microscope and all are sensitive to the phage chi. Unlike its parent, one of the mutants, studied in greater detail, failed to show chemotaxis toward oxygen, glucose, serine, threonine, or aspartic acid. The failure to exhibit chemotaxis does not result from a failure to use the chemicals. The swimming of this mutant was shown to be random. The growth rate was normal under several conditions, and the growth requirements were unchanged. Images PMID:5335897

  9. Adolescent reproductive health in Indonesia: contested values and policy inaction.

    PubMed

    Utomo, Iwu Dwisetyani; McDonald, Peter

    2009-06-01

    This study examines the changing social and political context of adolescent sexual and reproductive health policy in Indonesia. We describe how, in 2001, Indonesia was on the brink of implementing an adolescent reproductive health policy that was consistent with international agreements to which the Indonesian government was a party. Although the health of young Indonesians was known to be at risk, the opportunity for reform passed quickly with the emergence of a new competing force, Middle Eastern fundamentalist Islam. Faced with the risk of regional separatism and competing politico-religious influences, the Indonesian government retreated to the safety of inaction in this area of policy. In the absence of a supportive and committed political environment that reinforces policy specifically targeted to young people's reproductive health, extremist approaches that involve considerable health risk prevailed. The sexual and reproductive values and behaviors that are emerging among single young people in contemporary Indonesia are conditioned by a political context that allows the conflicting forces of traditional Indonesian values, Westernization, and the strong emerging force of fundamentalist Islam to compete for the allegiance of young people. PMID:19662805

  10. Genetic and pharmacological reactivation of the mammalian inactive X chromosome

    PubMed Central

    Bhatnagar, Sanchita; Zhu, Xiaochun; Ou, Jianhong; Lin, Ling; Chamberlain, Lynn; Zhu, Lihua J.; Wajapeyee, Narendra; Green, Michael R.

    2014-01-01

    X-chromosome inactivation (XCI), the random transcriptional silencing of one X chromosome in somatic cells of female mammals, is a mechanism that ensures equal expression of X-linked genes in both sexes. XCI is initiated in cis by the noncoding Xist RNA, which coats the inactive X chromosome (Xi) from which it is produced. However, trans-acting factors that mediate XCI remain largely unknown. Here, we perform a large-scale RNA interference screen to identify trans-acting XCI factors (XCIFs) that comprise regulators of cell signaling and transcription, including the DNA methyltransferase, DNMT1. The expression pattern of the XCIFs explains the selective onset of XCI following differentiation. The XCIFs function, at least in part, by promoting expression and/or localization of Xist to the Xi. Surprisingly, we find that DNMT1, which is generally a transcriptional repressor, is an activator of Xist transcription. Small-molecule inhibitors of two of the XCIFs can reversibly reactivate the Xi, which has implications for treatment of Rett syndrome and other dominant X-linked diseases. A homozygous mouse knockout of one of the XCIFs, stanniocalcin 1 (STC1), has an expected XCI defect but surprisingly is phenotypically normal. Remarkably, X-linked genes are not overexpressed in female Stc1−/− mice, revealing the existence of a mechanism(s) that can compensate for a persistent XCI deficiency to regulate X-linked gene expression. PMID:25136103

  11. Effects of Physical (In)activity on Platelet Function

    PubMed Central

    Heber, Stefan; Volf, Ivo

    2015-01-01

    As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (in)activity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects' cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i) acute, strenuous exercise can lead to platelet activation, (ii) regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii) habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality. PMID:26557653

  12. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now...

  13. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now...

  14. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now...

  15. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now...

  16. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now...

  17. Excess Medical Care Costs Associated with Physical Inactivity among Korean Adults: Retrospective Cohort Study.

    PubMed

    Min, Jin-Young; Min, Kyoung-Bok

    2016-01-01

    Physical inactivity is a major risk factor for chronic diseases and premature death. The increased health risks associated with physical inactivity may also generate a heavier economic burden to society. We estimated the direct medical costs attributable to physical inactivity among adults using data from the 2002-2010 Korean National Health Insurance Service-National Sample Cohort. A total of 68,556 adults whose reported physical activity status did not change during the study period was included for this study. Propensity scores for inactive adults were used to match 23,645 inactive groups with 23,645 active groups who had similar propensity scores. We compared medical expenditures between the two groups using generalized linear models with a gamma distribution and a log link. Direct medical costs were based on the reimbursement records of all medical facilities from 2005 to 2010. The average total medical costs for inactive individuals were $1110.5, which was estimated to be 11.7% higher than the costs for physically active individuals. With respect to specific diseases, the medical costs of inactive people were significantly higher than those of active people, accounting for approximately 8.7% to 25.3% of the excess burden. Physical inactivity is associated with considerable medical care expenditures per capita among Korean adults. PMID:26797622

  18. 10 CFR 40.2a - Coverage of inactive tailings sites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Coverage of inactive tailings sites. (a) Prior to the completion of the remedial action, the Commission will not require a license pursuant to 10 CFR chapter I for possession of residual radioactive... 10 Energy 1 2011-01-01 2011-01-01 false Coverage of inactive tailings sites. 40.2a Section...

  19. 10 CFR 40.2a - Coverage of inactive tailings sites.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Coverage of inactive tailings sites. (a) Prior to the completion of the remedial action, the Commission will not require a license pursuant to 10 CFR chapter I for possession of residual radioactive... 10 Energy 1 2012-01-01 2012-01-01 false Coverage of inactive tailings sites. 40.2a Section...

  20. 10 CFR 40.2a - Coverage of inactive tailings sites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Coverage of inactive tailings sites. (a) Prior to the completion of the remedial action, the Commission will not require a license pursuant to 10 CFR chapter I for possession of residual radioactive... 10 Energy 1 2010-01-01 2010-01-01 false Coverage of inactive tailings sites. 40.2a Section...

  1. 10 CFR 40.2a - Coverage of inactive tailings sites.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Coverage of inactive tailings sites. (a) Prior to the completion of the remedial action, the Commission will not require a license pursuant to 10 CFR chapter I for possession of residual radioactive... 10 Energy 1 2014-01-01 2014-01-01 false Coverage of inactive tailings sites. 40.2a Section...

  2. In Search of Lost Springs: A Protocol for Locating Active and Inactive Springs.

    PubMed

    Fensham, R J; Silcock, J L; Powell, O; Habermehl, M A

    2016-05-01

    Groundwater springs are significant landscape features for humans and the biota that occupies their habitat. Many springs become inactive where groundwater exploitation by humans has lowered the water table or artesian pressure. In order to assess this impact, it is important to identify and locate active, and with more difficulty, inactive springs. Using a variety of archival, environmental and field-based data, this study presents a protocol for the determination of the location and status of springs across the Great Artesian Basin of Australia. This protocol underpins a database of springs, which is not only important for the assessment of spring ecosystems, but also contributes to understand groundwater extraction impacts and hydrogeological processes. The database indicates that 30.0% of discharge (artesian) springs in the Great Artesian Basin are entirely inactive and another 11.8% are partially inactive. For the outcrop (gravity) springs of the Basin, only 1.9% are entirely inactive and 7.4% partially inactive, and for the outcrop springs in the Tertiary sandstone overlying the Basin 30.9% are inactive and 18.2% are partially inactive. PMID:26436535

  3. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types... practitioner take and pass a professional responsibility examination. (c) Transfer to disability...

  4. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types... practitioner take and pass a professional responsibility examination. (c) Transfer to disability...

  5. Motility mutants of Dictyostelium discoideum

    PubMed Central

    1982-01-01

    We describe six motility mutants of Dictyostelium discoideum in this report. They were identified among a group of temperature-sensitive growth (Tsg) mutants that had been previously isolated using an enrichment for phagocytosis-defective cells. The Tsg mutants were screened for their ability to produce tracks on gold-coated cover slips, and several strains were found that were temperature-sensitive for migration in this assay. Analysis of spontaneous Tsg+ revertants of 10 migration-defective strains identified six strains that co-reverted the Tsg and track formation phenotypes. Characterization of these six strains indicated that they were defective at restrictive temperature in track formation, phagocytosis of bacteria, and pseudopodial and filopodial activity, while retaining normal rates of oxygen consumption and viability. Because they had lost this group of motile capabilities, these strains were designated motility mutants. The Tsg+ revertants of these mutants, which coordinately recovered all of the motile activities, were found at frequencies consistent with single genetic events. Analysis of the motility mutants and their revertants suggests a relationship between the motility mutations in some of these strains and genes affecting axenic growth. PMID:7118999

  6. Predictors of physical inactivity among elderly malaysians: recommendations for policy planning.

    PubMed

    Kaur, Jasvindar; Kaur, Gurpreet; Ho, Bee Kiau; Yao, Weng Keong; Salleh, Mohmad; Lim, Kuang Hock

    2015-04-01

    Physical inactivity is the fourth leading risk factor for global mortality. Regular moderate-intensity physical activity has significant benefits for health. To determine the socioeconomic predictors of physical inactivity among elderly Malaysian population. A nationwide community-based survey was conducted among 4831 respondents aged ≥60 years with a face-to-face questionnaire. The prevalence of physical inactivity among the elderly was 88.0%, highest in respondents aged older than 80 years (95.4%), females (90.1%), other Bumiputra (92.2%), earning household income less than RM1000 (87.9%), and residing in urban locality (88.4%). In the multivariate model, the predictors of physical inactivity were only sex, ethnicity, locality, and age group (adjusted odds ratio = 1.3-3.6). The predictors of physical inactivity can identify the risk factors to develop policies that will reduce the public health burden of noncommunicable diseases. PMID:24425796

  7. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

    PubMed Central

    Lito, Piro; Solomon, Martha; Li, Lian-Sheng; Hansen, Rasmus; Rosen, Neal

    2016-01-01

    It is thought that KRAS oncoproteins are constitutively active because their guanosine triphosphatase (GTPase) activity is disabled. Consequently, drugs targeting the inactive or guanosine 5′-diphosphate–bound conformation are not expected to be effective. We describe a mechanism that enables such drugs to inhibit KRASG12C signaling and cancer cell growth. Inhibition requires intact GTPase activity and occurs because drug-bound KRASG12C is insusceptible to nucleotide exchange factors and thus trapped in its inactive state. Indeed, mutants completely lacking GTPase activity and those promoting exchange reduced the potency of the drug. Suppressing nucleotide exchange activity downstream of various tyrosine kinases enhanced KRASG12C inhibition, whereas its potentiation had the opposite effect. These findings reveal that KRASG12C undergoes nucleotide cycling in cancer cells and provide a basis for developing effective therapies to treat KRASG12C-driven cancers. PMID:26841430

  8. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism.

    PubMed

    Lito, Piro; Solomon, Martha; Li, Lian-Sheng; Hansen, Rasmus; Rosen, Neal

    2016-02-01

    It is thought that KRAS oncoproteins are constitutively active because their guanosine triphosphatase (GTPase) activity is disabled. Consequently, drugs targeting the inactive or guanosine 5'-diphosphate-bound conformation are not expected to be effective. We describe a mechanism that enables such drugs to inhibit KRAS(G12C) signaling and cancer cell growth. Inhibition requires intact GTPase activity and occurs because drug-bound KRAS(G12C) is insusceptible to nucleotide exchange factors and thus trapped in its inactive state. Indeed, mutants completely lacking GTPase activity and those promoting exchange reduced the potency of the drug. Suppressing nucleotide exchange activity downstream of various tyrosine kinases enhanced KRAS(G12C) inhibition, whereas its potentiation had the opposite effect. These findings reveal that KRAS(G12C) undergoes nucleotide cycling in cancer cells and provide a basis for developing effective therapies to treat KRAS(G12C)-driven cancers. PMID:26841430

  9. Anti-HIV Activity of Defective Cyanovirin-N Mutants Is Restored by Dimerization*

    PubMed Central

    Matei, Elena; Zheng, Andrew; Furey, William; Rose, Jeremy; Aiken, Christopher; Gronenborn, Angela M.

    2010-01-01

    Cyanovirin-N (CV-N) is a two-domain, cyanobacterial protein that inhibits human immunodeficiency virus (HIV) at nanomolar concentrations by binding to high mannose sugars on the HIV envelope glycoprotein gp120. The wild type protein can exist as a monomer or a domain-swapped dimer with the monomer and dimer containing two or four sugar binding sites, respectively, one on each domain. Here we demonstrate that monomeric, single binding site mutants are completely inactive and that a single site, whether located on domain A or B, is insufficient to impart the antiviral activity. Linking inactive, monomeric proteins in a head-to-head fashion by an intermolecular disulfide bond or by creating an exclusively domain-swapped dimer via a hinge residue deletion restored antiviral activity to levels similar to that of wild type CV-N. These findings demonstrate unequivocally that multisite binding by CV-N type lectins is necessary for viral inhibition. PMID:20147291

  10. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis

    PubMed Central

    Motl, R. W.; Goldman, M.

    2011-01-01

    Objective We examined the associations among physical activity, neurological disability, and cardiorespiratory fitness in two studies of individuals with multiple sclerosis (MS). Method Study 1 included 25 women with relapsing-remitting MS (RRMS) who undertook an incremental exercise test for measuring peak oxygen (V̇O2peak) consumption, wore an accelerometer during a 7-day period, and completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Study 2 was a follow-up of Study 1 and included 24 women with RRMS who completed the self-reported Expanded Disability Status Scale (EDSS), undertook an incremental exercise test, wore an accelerometer during a 7-day period, and completed the GLTEQ. Results Study 1 indicated that V̇O2peak was significantly correlated with accelerometer counts (pr = 0.69) and GLTEQ scores (pr = 0.63) even after controlling for age and MS duration. Study 2 indicated that V̇O2peak was significantly correlated with accelerometer counts (pr = 0.50), GLTEQ scores (pr = 0.59), and EDSS scores (pr = −0.43) even after controlling for age and MS duration; there was a moderate partial correlation between accelerometer counts and EDSS scores (pr = −0.43). Multiple linear regression analysis indicated that both accelerometer counts (β = 0.32) and EDSS scores (β = −0.40) had statistically significant associations with V̇O2peak. Conclusion The findings indicate that physical inactivity and neurological disability might represent independent risk factors for reduced levels of cardiorespiratory fitness in this population. PMID:21108624

  11. Effects of Physical Activity and Inactivity on Muscle Fatigue

    PubMed Central

    Bogdanis, Gregory C.

    2012-01-01

    The aim of this review was to examine the mechanisms by which physical activity and inactivity modify muscle fatigue. It is well known that acute or chronic increases in physical activity result in structural, metabolic, hormonal, neural, and molecular adaptations that increase the level of force or power that can be sustained by a muscle. These adaptations depend on the type, intensity, and volume of the exercise stimulus, but recent studies have highlighted the role of high intensity, short-duration exercise as a time-efficient method to achieve both anaerobic and aerobic/endurance type adaptations. The factors that determine the fatigue profile of a muscle during intense exercise include muscle fiber composition, neuromuscular characteristics, high energy metabolite stores, buffering capacity, ionic regulation, capillarization, and mitochondrial density. Muscle fiber-type transformation during exercise training is usually toward the intermediate type IIA at the expense of both type I and IIx myosin heavy-chain isoforms. High-intensity training results in increases of both glycolytic and oxidative enzymes, muscle capillarization, improved phosphocreatine resynthesis and regulation of K+, H+, and lactate ions. Decreases of the habitual activity level due to injury or sedentary lifestyle result in partial or even compete reversal of the adaptations due to previous training, manifested by reductions in fiber cross-sectional area, decreased oxidative capacity, and capillarization. Complete immobilization due to injury results in markedly decreased force output and fatigue resistance. Muscle unloading reduces electromyographic activity and causes muscle atrophy and significant decreases in capillarization and oxidative enzymes activity. The last part of the review discusses the beneficial effects of intermittent high-intensity exercise training in patients with different health conditions to demonstrate the powerful effect of exercise on health and well being. PMID

  12. The prognosis and management of inactive HBV carriers.

    PubMed

    Invernizzi, Federica; Viganò, Mauro; Grossi, Glenda; Lampertico, Pietro

    2016-01-01

    Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1 year, while a single-point detection of combined HBsAg <1000 IU/ml and HBV DNA <2000 IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5 kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12 months with periodic measurement of serum HBsAg levels to identify viral clearance. PMID:26725905

  13. Comprehensive Management Strategies for Physical Inactivity in Youth

    PubMed Central

    MYER, GREGORY D.; FAIGENBAUM, AVERY D.; STRACCIOLINI, ANDREA; HEWETT, TIMOTHY E.; MICHELI, LYLE J.; BEST, THOMAS M.

    2013-01-01

    Despite the widely recognized benefits of daily play, recreation, sports, and physical education on the physical and psychosocial well-being of children and adolescents, many contemporary children and adolescents worldwide do not meet the recommendations for daily physical activity. The decline in physical activity seems to start early in life which leads to conditions characterized by reduced levels of physical activity in the pediatric population that are inconsistent with current public health recommendations. Unlike many other diseases and disorders in pediatrics, physical inactivity in youth is unique in that it currently lacks a clinical gold standard for diagnosis. This makes the diagnosis and treatment medically challenging, though no less important, as the resultant ramifications of a missed diagnosis are of significant detriment. Exercise deficient children need to be identified early in life and treated with developmentally appropriate exercise programs designed to target movement deficiencies and physical weaknesses in a supportive environment. Without such interventions early in life, children are more likely to become resistant to our interventions later in life and consequently suffer from adverse health consequences. Integrative approaches that link health care professionals, pediatric exercise specialists, school administrators, community leaders, and policy makers, may provide the best opportunity to promote daily physical activity, reinforce desirable behaviors, and educate parents about the exercise-health link. If health care providers miss the window of opportunity to identify exercise deficit disorder in youth and promote healthy lifestyle choices, the eventual decline and disinterest in physical activity will begin to take shape and new health care concerns will continue to emerge. PMID:23851413

  14. Embryo and endosperm development is disrupted in the female gametophytic capulet mutants of Arabidopsis.

    PubMed Central

    Grini, Paul E; Jürgens, Gerd; Hülskamp, Martin

    2002-01-01

    The female gametophyte of higher plants gives rise, by double fertilization, to the diploid embryo and triploid endosperm, which develop in concert to produce the mature seed. What roles gametophytic maternal factors play in this process is not clear. The female-gametophytic effects on embryo and endosperm development in the Arabidopsis mea, fis, and fie mutants appear to be due to gametic imprinting that can be suppressed by METHYL TRANSFERASE1 antisense (MET1 a/s) transgene expression or by mutation of the DECREASE IN DNA METHYLATION1 (DDM1) gene. Here we describe two novel gametophytic maternal-effect mutants, capulet1 (cap1) and capulet2 (cap2). In the cap1 mutant, both embryo and endosperm development are arrested at early stages. In the cap2 mutant, endosperm development is blocked at very early stages, whereas embryos can develop to the early heart stage. The cap mutant phenotypes were not rescued by wild-type pollen nor by pollen from tetraploid plants. Furthermore, removal of silencing barriers from the paternal genome by MET1 a/s transgene expression or by the ddm1 mutation also failed to restore seed development in the cap mutants. Neither cap1 nor cap2 displayed autonomous seed development, in contrast to mea, fis, and fie mutants. In addition, cap2 was epistatic to fis1 in both autonomous endosperm and sexual development. Finally, both cap1 and cap2 mutant endosperms, like wild-type endosperms, expressed the paternally inactive endosperm-specific FIS2 promoter GUS fusion transgene only when the transgene was introduced via the embryo sac, indicating that imprinting was not affected. Our results suggest that the CAP genes represent novel maternal functions supplied by the female gametophyte that are required for embryo and endosperm development. PMID:12524359

  15. Construction and characterization of recombinant Vibrio cholerae strains producing inactive cholera toxin analogs.

    PubMed

    Häse, C C; Thai, L S; Boesman-Finkelstein, M; Mar, V L; Burnette, W N; Kaslow, H R; Stevens, L A; Moss, J; Finkelstein, R A

    1994-08-01

    The catalytic A subunit of cholera toxin (CT-A) is capable of ADP-ribosylating the guanine nucleotide-binding protein, which regulates cell adenylyl cyclase, leading to the life-threatening diarrhea of cholera. Amino acids involved in the enzymatic activity of CT-A have previously been identified. By means of site-directed mutagenesis, an analog of the CT-A subunit gene was created with codon substitutions for both Arg-7 and Glu-112, each of which has been shown to produce subunits lacking ADP-ribosyltransferase activity. The mutated gene fragment was exchanged for the wild-type copy in the previously cloned ctxAB operon from El Tor biotype, Ogawa serotype Vibrio cholerae strain 3083, which produces CT-2. Further, the zonula occludens toxin gene, zot, was inactivated by an insertional mutation to create the new plasmid construct pCT-2*. Additionally, a DNA fragment encoding the B subunit of CT-1 (CT produced by classical biotype, Inaba serotype V. cholerae strain 569B) was exchanged for the homologous part in pCT-2*, resulting in the creation of pCT-1*. These plasmid constructs were introduced into the CT-negative V. cholerae mutant strain JBK70 (E1 Tor biotype, Inaba serotype); CT-A-B+ derivatives CVD101 and CVD103 of classical biotype Ogawa and Inaba serotype strains 395 and 569B, respectively; El Tor biotype Inaba and Ogawa serotype strains C6706 and C7258, respectively, recently isolated in Peru; and O139 (synonym Bengal) strain SG25-1 from the current epidemic in India. Recombinant toxins (CT-1* and CT-2*), partially purified from culture supernatants of transformed JBK70, were shown to be inactive on mouse Y1 adrenal tumor cells and in an in vitro ADP-ribosyltransferase assay. CT-1* and CT-2* reacted with polyclonal and monoclonal antibodies against both A and B subunits of CT. The toxin analogs reacted with antibodies against CT-A and CT-B on cellulose acetate strips and in a GM1 enzyme-linked immunosorbent assay; they reacted appropriately with B

  16. Misassembled mutant DeltaF508 CFTR in the distal secretory pathway alters cellular lipid trafficking.

    PubMed

    Gentzsch, Martina; Choudhury, Amit; Chang, Xiu-bao; Pagano, Richard E; Riordan, John R

    2007-02-01

    Most patients with cystic fibrosis (CF) have a single codon deletion (DeltaF508) in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that impairs assembly of the multidomain glycoprotein. The mutant protein escapes endoplasmic reticulum (ER) quality control at low temperature, but is rapidly cleared from the distal secretory pathway and degraded in lysosomes. CF cells accumulate free cholesterol similar to Niemann-Pick disease type C cells. We show that this lipid alteration is caused by the presence of misassembled mutant CFTR proteins, including DeltaF508, in the distal secretory pathway rather than the absence of functional CFTR. By contrast, cholesterol distribution is not changed by either D572N CFTR, which does not mature even at low temperature, or G551D, which is processed normally but is inactive. On expression of the DeltaF508 mutant, cholesterol and glycosphingolipids accumulate in punctate endosomal structures and cholesterol esters are reduced, indicating a block in the translocation of cholesterol to the ER for esterification. This is overcome by Rab9 overexpression, resulting in clearance of accumulating intracellular cholesterol. Similar but less pronounced alterations in intracellular cholesterol distribution are observed on expression of a temperature-rescued mutant variant of the related ATP-binding cassette (ABC) protein multidrug resistance-associated protein 1 (MRP1). Thus, on escape from ER quality control, misassembled mutants of CFTR and MRP1 impair lipid homeostasis in endocytic compartments. PMID:17213331

  17. SEMINAR PUBLICATION: MANAGING ENVIRONMENTAL PROBLEMS AT INACTIVE AND ABANDONED METALS MINE SITES

    EPA Science Inventory

    Environmental problems associated with abandoned and inactive mines are addressed along with some approaches to resolving those problems, including case studies demonstrating technologies that have worked. New technologies being investigated are addressed also.

  18. A new light on DNA replication from the inactive X chromosome

    PubMed Central

    Aladjem, Mirit I.; Fu, Haiqing

    2014-01-01

    While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, “silent” chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular. PMID:24706495

  19. Increasing and Decreasing Motor and Cognitive Output: A Model of General Action and Inaction Goals

    PubMed Central

    Albarracín, Dolores; Handley, Ian M.; Noguchi, Kenji; McCulloch, Kathleen C.; Li, Hong; Leeper, Joshua; Brown, Rick D.; Earl, Allison; Hart, William P.

    2013-01-01

    General action and inaction goals can influence the amount of motor or cognitive output irrespective of the type of behavior in question, with the same stimuli producing trivial and important motor and cognitive manifestations normally viewed as parts of different systems. A series of experiments examined the effects of instilling general action and inaction goals using word primes, such as “action” and “rest.” The first 5 experiments showed that the same stimuli influenced motor output, such as doodling on a piece of paper and eating, as well as cognitive output, such as recall and problem solving. The last 2 experiments supported the prediction that these diverse effects can result from the instigation of general action and inaction goals. Specifically, these last 2 studies confirmed that participants were motivated to achieve active or inactive states and that attaining them decreased the effects of the primes on behavior. PMID:18729691

  20. Evidence for a Chemoautotrophically Based Food Web at Inactive Hydrothermal Vents (Manus Basin)

    NASA Astrophysics Data System (ADS)

    van Dover, C. L.; Erickson, K.; Macko, S.

    2008-12-01

    Hydrothermal vents are ephemeral systems. When venting shuts down, sulfide-dependent taxa die off, and non-vent taxa can colonize the hard substrata. In Manus Basin (Papua New Guinea), where active and inactive sulfide mounds are interspersed, hydroids, cladorhizid sponges, barnacles, and bamboo sponges, and other invertebrate types may occupy inactive sulfide mounds. Carbon and nitrogen isotopic compositions of animals occupying inactive sulfide mounds are consistent with nutritional dependence on either chemoautotrophically or photosynthetically produced organic material, but sulfur isotopic compositions of these animals point to a chemoautotrophic source of sulfur from dissolved sulfide in vent fluids rather than sulfur derived from seawater sulfate through photosynthesis. Given that suspension-feeding and micro- carnivorous invertebrates are the biomass dominants at inactive sulfide mounds, the primary source of chemoautotrophic nutrition is likely suspended particulates and organisms delivered from nearby active vents.

  1. Evidence for a chemoautotrophically based food web at inactive hydrothermal vents (Manus Basin)

    NASA Astrophysics Data System (ADS)

    Erickson, K. L.; Macko, S. A.; Van Dover, C. L.

    2009-09-01

    Hydrothermal vents are ephemeral systems. When venting shuts down, sulfide-dependent taxa die off, and non-vent taxa can colonize the hard substrata. In Manus Basin (Papua New Guinea), where hydrothermally active and inactive sites are interspersed, hydroids, cladorhizid sponges, barnacles, bamboo corals, and other invertebrate types may occupy inactive sites. Carbon and nitrogen isotopic compositions of animals occupying inactive sites are consistent with nutritional dependence on either chemoautotrophically or photosynthetically produced organic material, but sulfur isotopic compositions of these animals point to a chemoautotrophic source of sulfur from dissolved sulfide in vent fluids rather than sulfur derived from seawater sulfate through photosynthesis. Given that suspension-feeding and micro-carnivorous invertebrates are the biomass dominants at inactive sites, the primary source of chemoautotrophic nutrition is likely suspended particulates and organisms delivered from nearby active vents.

  2. Patterns of association between environmental quality and physical inactivity vary across the rural-urban continuum

    EPA Science Inventory

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Many studies have shown associations between specific environmental features (la...

  3. Using a novel environmental quality measure to understand population-level physical inactivity

    EPA Science Inventory

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Understanding the role of the overall ambient environment in population inactivi...

  4. Prevalence and Correlates of Physical Inactivity among Older Adults in Rio Grande do Sul, Brazil

    PubMed Central

    Souza, Adelle M. R.; Fillenbaum, Gerda G.; Blay, Sergio L.

    2015-01-01

    Background Current information on the epidemiology of physical inactivity among older adults is lacking, making it difficult to target the inactive and to plan for interventions to ameliorate adverse effects. Objectives To present statewide representative findings on the prevalence of physical inactivity among older community residents, its correlates and associated health service use. Methods A representative non-institutionalized random sample of 6963 individuals in Rio Grande do Sul, Brazil, aged ≥60 years, was interviewed face-to-face. Information was obtained on demographic characteristics, social resources, health conditions and behaviors, health service use, and physical inactivity. Controlled logistic regression was used to determine the association of physical inactivity with these characteristics. Results Overall, 62% reported no regular physical activity. Physical inactivity was significantly more prevalent among women, older persons, those with lower education and income, Afro-Brazilians (73%; White: 61%; “other”: 64%), those no longer married, and was associated with multiple individual health conditions and impaired activities of daily living (ADL). In adjusted analyses, associations remained for sociodemographic characteristics, social participation, impaired self-rated health, ADL, vision, and depression (odds ratios (OR) 1.2–1.7). Physically inactive respondents were less likely to report outpatient visits (OR 0.81), but more likely to be hospitalized (OR 1.41). Conclusions Physical inactivity is highly prevalent, particularly among Afro -Brazilians. It is associated with adverse sociodemographic characteristics; lack of social interaction; and poor self-rated health, ADL, vision, and depression; although not with other health conditions. Self-care may be neglected, resulting in hospitalization. PMID:25700161

  5. Population attributable fraction of type 2 diabetes due to physical inactivity in adults: a systematic review

    PubMed Central

    2014-01-01

    Background Physical inactivity is a global pandemic. The population attributable fraction (PAF) of type 2 diabetes mellitus (T2DM) associated with physical inactivity ranges from 3% to 40%. The purpose of this systematic review was to determine the best estimate of PAF for T2DM attributable to physical inactivity and absence of sport participation or exercise for men and women. Methods We conducted a systematic review that included a comprehensive search of MEDLINE, EMBASE, SportDiscus, and CINAHL (1946 to April 30 2013) limited by the terms adults and English. Two reviewers screened studies, extracted PAF related data and assessed the quality of the selected studies. We reconstructed 95% CIs for studies missing these data using a substitution method. Results Of the eight studies reporting PAF in T2DM, two studies included prospective cohort studies (3 total) and six were reviews. There were distinct variations in quality of defining and measuring physical inactivity, T2DM and adjusting for confounders. In the US, PAFs for absence of playing sport ranged from 13% (95% CI: 3, 22) in men and 29% (95% CI: 17, 41) in women. In Finland, PAFs for absence of exercise ranged from 3% (95% CI: -11, 16) in men to 7% (95% CI: -9, 20) in women. Conclusions The PAF of physical inactivity due to T2DM is substantial. Physical inactivity is a modifiable risk factor for T2DM. The contribution of physical inactivity to T2DM differs by sex; PAF also differs if physical inactivity is defined as the absence of ‘sport’ or absence of ‘exercise’. PMID:24885278

  6. Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA.

    PubMed

    Richardson, Christopher D; Ray, Graham J; DeWitt, Mark A; Curie, Gemma L; Corn, Jacob E

    2016-03-01

    Targeted genomic manipulation by Cas9 can efficiently generate knockout cells and organisms via error-prone nonhomologous end joining (NHEJ), but the efficiency of precise sequence replacement by homology-directed repair (HDR) is substantially lower. Here we investigate the interaction of Cas9 with target DNA and use our findings to improve HDR efficiency. We show that dissociation of Cas9 from double-stranded DNA (dsDNA) substrates is slow (lifetime ∼6 h) but that, before complete dissociation, Cas9 asymmetrically releases the 3' end of the cleaved DNA strand that is not complementary to the sgRNA (nontarget strand). By rationally designing single-stranded DNA (ssDNA) donors of the optimal length complementary to the strand that is released first, we increase the rate of HDR in human cells when using Cas9 or nickase variants to up to 60%. We also demonstrate HDR rates of up to 0.7% using a catalytically inactive Cas9 mutant (dCas9), which binds DNA without cleaving it. PMID:26789497

  7. Motives for physical activity among active and inactive persons in their mid-30s.

    PubMed

    Aaltonen, S; Rottensteiner, M; Kaprio, J; Kujala, U M

    2014-08-01

    The purpose of this study was to examine the motives for leisure-time physical activity among active and inactive men and women in their mid-30s. We used both cross-sectional and longitudinal designs. Altogether, 2308 participants (mean age 33.9 years, 53.4% women) were identified from the population-based FinnTwin16 Cohort. Physically active and inactive individuals were identified on the basis of their leisure-time MET h/day. We evaluated participants' physical activity motivation with a modified version of the Recreational Exercise Motivation Measure. Comparisons between active and inactive individuals were analysed using the Wald test for equality of means, and effect sizes were calculated as Cohen's d. Motives related to mastery, physical fitness, social aspect of physical activity, psychological state, enjoyment, willingness to be fitter/look better than others, and appearance were significantly more important for the active than inactive participants. Conforming to others' expectations was the only item on which the inactive persons scored higher than active persons. The longitudinal results for physical activity were parallel to the cross-sectional results. This study supports the view that motivation factors differ between active and inactive persons, and that intrinsic motives are associated with consistent leisure-time physical activity. PMID:23331765

  8. The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer.

    PubMed

    Chaligné, Ronan; Popova, Tatiana; Mendoza-Parra, Marco-Antonio; Saleem, Mohamed-Ashick M; Gentien, David; Ban, Kristen; Piolot, Tristan; Leroy, Olivier; Mariani, Odette; Gronemeyer, Hinrich; Vincent-Salomon, Anne; Stern, Marc-Henri; Heard, Edith

    2015-04-01

    Disappearance of the Barr body is considered a hallmark of cancer, although whether this corresponds to genetic loss or to epigenetic instability and transcriptional reactivation is unclear. Here we show that breast tumors and cell lines frequently display major epigenetic instability of the inactive X chromosome, with highly abnormal 3D nuclear organization and global perturbations of heterochromatin, including gain of euchromatic marks and aberrant distributions of repressive marks such as H3K27me3 and promoter DNA methylation. Genome-wide profiling of chromatin and transcription reveal modified epigenomic landscapes in cancer cells and a significant degree of aberrant gene activity from the inactive X chromosome, including several genes involved in cancer promotion. We demonstrate that many of these genes are aberrantly reactivated in primary breast tumors, and we further demonstrate that epigenetic instability of the inactive X can lead to perturbed dosage of X-linked factors. Taken together, our study provides the first integrated analysis of the inactive X chromosome in the context of breast cancer and establishes that epigenetic erosion of the inactive X can lead to the disappearance of the Barr body in breast cancer cells. This work offers new insights and opens up the possibility of exploiting the inactive X chromosome as an epigenetic biomarker at the molecular and cytological levels in cancer. PMID:25653311

  9. The solution configurations of inactive and activated DntR have implications for the sliding dimer mechanism of LysR transcription factors

    PubMed Central

    Lerche, Michael; Dian, Cyril; Round, Adam; Lönneborg, Rosa; Brzezinski, Peter; Leonard, Gordon A.

    2016-01-01

    LysR Type Transcriptional Regulators (LTTRs) regulate basic metabolic pathways or virulence gene expression in prokaryotes. Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo- configuration that represses transcription to an active, expanded holo- form that promotes it. However, no LTTR has yet been observed to adopt both configurations. Here, we report the results of structural studies of various forms of the LTTR DntR. Crystal structures of apo-DntR and of a partially autoinducing mutant H169T-DntR suggest that active and inactive DntR maintain a compact homotetrameric configuration. However, Small Angle X-ray Scattering (SAXS) studies on solutions of apo-, H169T- and inducer-bound holo-DntR indicate a different behaviour, suggesting that while apo-DntR maintains a compact configuration in solution both H169T- and holo-DntR adopt an expanded conformation. Models of the SAXS-obtained solution conformations of apo- and holo-DntR homotetramers in complex with promoter-operator region DNA are consistent with previous observations of a shifting of LTTR DNA binding sites upon activation and a consequent relaxation in the bend of the promoter-operator region DNA. Our results thus provide clear evidence at the molecular level which strongly supports the ‘sliding dimer’ hypothesis concerning LTTR activation mechanisms. PMID:26817994

  10. Arabidopsis mutants impaired in cosuppression.

    PubMed Central

    Elmayan, T; Balzergue, S; Béon, F; Bourdon, V; Daubremet, J; Guénet, Y; Mourrain, P; Palauqui, J C; Vernhettes, S; Vialle, T; Wostrikoff, K; Vaucheret, H

    1998-01-01

    Post-transcriptional gene silencing (cosuppression) results in the degradation of RNA after transcription. A transgenic Arabidopsis line showing post-transcriptional silencing of a 35S-uidA transgene and uidA-specific methylation was mutagenized using ethyl methanesulfonate. Six independent plants were isolated in which uidA mRNA accumulation and beta-glucuronidase activity were increased up to 3500-fold, whereas the transcription rate of the 35S-uidA transgene was increased only up to threefold. These plants each carried a recessive monogenic mutation that is responsible for the release of silencing. These mutations defined two genetic loci, called sgs1 and sgs2 (for suppressor of gene silencing). Transgene methylation was distinctly modified in sgs1 and sgs2 mutants. However, methylation of centromeric repeats was not affected, indicating that sgs mutants differ from ddm (for decrease in DNA methylation) and som (for somniferous) mutants. Indeed, unlike ddm and som mutations, sgs mutations were not able to release transcriptional silencing of a 35S-hpt transgene. Conversely, both sgs1 and sgs2 mutations were able to release cosuppression of host Nia genes and 35S-Nia2 transgenes. These results therefore indicate that sgs mutations act in trans to impede specifically transgene-induced post-transcriptional gene silencing. PMID:9761800

  11. Problem-Solving Test: Tryptophan Operon Mutants

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  12. Grain Development Mutants of Barley ([alpha]-Amylase Production during Grain Maturation and Its Relation to Endogenous Gibberellic Acid Content).

    PubMed Central

    Green, L. S.; Faergestad, E. M.; Poole, A.; Chandler, P. M.

    1997-01-01

    Barley (Hordeum vulgare L. Himalaya) mutants with altered grain morphology were isolated to investigate whether defects in grain development, possibly involving gibberellins (GAs) and abscisic acid, would lead to altered patterns of [alpha]-amylase gene expression. Following treatment with sodium azide, 75 mutants, typically showing grain shriveling, were identified. At grain maturity 15 of the 75 mutants had higher [alpha]-amylase activities in shriveled grains compared with either phenotypically normal grains that developed on the same heterozygous plant or with grains of cv Himalaya. Studies of four of these mutants demonstrated increased levels of both high- and low-isoelectric point [alpha]-amylase isozymes midway through grain development. This category of mutant has been designated pga, for premature grain [alpha]-amylase. One such mutant (M326) showed an endosperm-determined inheritance pattern. When crossed into a (GA-deficient) dwarfing background there was a 10- to 20-fold reduction in [alpha]-amylase activity, suggesting a requirement for GA biosynthesis. Endogenous GAs and abscisic acid were quantified by combined gas chromatography-specific ion monitoring in normal and mutant grains of heterozygous M326 plants during the period of [alpha]-amylase accumulation. Mutant grains had significantly higher (5.8-fold) levels of the bioactive GA1 compared with normal grains but much lower (approximately 10-fold) levels of the 2[beta]-hydroxylated ("inactive") GAs, typical of developing barley grains (e.g. GA8, GA34, GA48). We propose that a reduced extent of 2[beta]-hydroxylation in the mutant grains results in an increased level of GA1, which is responsible for premature [alpha]-amylase gene expression. PMID:12223700

  13. Mechanism of the Anticoagulant Activity of Thrombin Mutant W215A/E217A

    SciTech Connect

    Gandhi, Prafull S.; Page, Michael J.; Chen, Zhiwei; Bush-Pelc, Leslie; Di Cera, Enrico

    2009-09-15

    The thrombin mutant W215A/E217A (WE) is a potent anticoagulant both in vitro and in vivo. Previous x-ray structural studies have shown that WE assumes a partially collapsed conformation that is similar to the inactive E* form, which explains its drastically reduced activity toward substrate. Whether this collapsed conformation is genuine, rather than the result of crystal packing or the mutation introduced in the critical 215-217 {beta}-strand, and whether binding of thrombomodulin to exosite I can allosterically shift the E* form to the active E form to restore activity toward protein C are issues of considerable mechanistic importance to improve the design of an anticoagulant thrombin mutant for therapeutic applications. Here we present four crystal structures of WE in the human and murine forms that confirm the collapsed conformation reported previously under different experimental conditions and crystal packing. We also present structures of human and murine WE bound to exosite I with a fragment of the platelet receptor PAR1, which is unable to shift WE to the E form. These structural findings, along with kinetic and calorimetry data, indicate that WE is strongly stabilized in the E* form and explain why binding of ligands to exosite I has only a modest effect on the E*-E equilibrium for this mutant. The E* {yields} E transition requires the combined binding of thrombomodulin and protein C and restores activity of the mutant WE in the anticoagulant pathway.

  14. Biochemical Characterization of a Spearmint Mutant That Resembles Peppermint in Monoterpene Content 1

    PubMed Central

    Croteau, Rodney; Karp, Frank; Wagschal, Kurt C.; Satterwhite, D. Michael; Hyatt, David C.; Skotland, Calvin B.

    1991-01-01

    A radiation-induced mutant of Scotch spearmint (Mentha × gracilis) was shown to produce an essential oil containing principally C3-oxygenated p-menthane monoterpenes that are typical of peppermint, instead of the C6-oxygenated monoterpene family characteristic of spearmint. In vitro measurement of all of the enzymes responsible for the production of both the C3-oxygenated and C6-oxygenated families of monoterpenes from the common precursor (−)-limonene indicated that a virtually identical complement of enzymes was present in wild type and mutant, with the exception of the microsomal, cytochrome P-450-dependent (−)-limonene hydroxylase; the C6-hydroxylase producing (−)-trans-carveol in the wild type had been replaced by a C3-hydroxylase producing (−)-trans-isopiperitenol in the mutant. Additionally, the mutant, but not the wild type, could carry out the cytochrome P-450-dependent epoxidation of the α,β-unsaturated bond of the ketones formed via C3-hydroxylation. Although present in the wild type, the enzymes of the C3-pathway that convert trans-isopiperitenol to menthol isomers are synthetically inactive because of the absence of the key C3-oxygenated intermediate generated by hydroxylation of limonene. These results, which clarify the origins of the C3- and C6-oxygenation patterns, also allow correction of a number of earlier biogenetic proposals for the formation of monoterpenes in Mentha. PMID:16668250

  15. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States

    PubMed Central

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-01-01

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA’s influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence—influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being. PMID:27548195

  16. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States.

    PubMed

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan

    2016-01-01

    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA's influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence-influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being. PMID:27548195

  17. Physical inactivity and anthropometric measures in schoolchildren from Paranavaí, Paraná, Brazil

    PubMed Central

    Guilherme, Flávio Ricardo; Molena-Fernandes, Carlos Alexandre; Guilherme, Vânia Renata; Fávero, Maria Teresa Martins; dos Reis, Eliane Josefa Barbosa; Rinaldi, Wilson

    2015-01-01

    OBJECTIVE: To investigate the association between physical inactivity and anthropometric measures in schoolchildren from Paranavaí-Parana, Brazil. METHODS: Cross-sectional survey, carried out in July and August 2013. Sample of 566 students (287 boys and 279 girls) from 6th to 9th grade, aged 10 to 14 years, from public and private schools of Paranavaí - PR, Southern Brazil. The variables analyzed were: time of weekly physical activity through a questionnaire (physical inactivity <300 minutes/week), body mass index (BMI) and waist circumference (WC). In the statistical analysis, the U Mann-Whitney and Student's t tests were used for comparison between genders. To identify factors associated with insufficient levels of physical activity, univariate and multivariate logistic regression analysis was applied and expressed in Odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: There was an association between physical inactivity and anthropometric measurements for BMI (p<0.001) and WC (p<0.001), with a prevalence rate of 56.1% and 52.7% of inactive adolescents, respectively. In the multivariate analysis, there was significant association of physical inactivity and overweight (OR 1.8, 95%CI: 1.1-3.0) and with increased waist circumference (OR 2.8, 95%CI: 1.4-3.8). CONCLUSIONS: Inadequate levels of physical activity is a determining factor for overweight and abdominal adiposity. Accordingly, preventive measures should be taken, especially in schools, emphasizing the importance of exercise for body composition control and weight reduction. PMID:25623726

  18. Economic burden of physical inactivity: healthcare costs associated with cardiovascular disease.

    PubMed

    Oldridge, Neil B

    2008-04-01

    Increasingly important objectives for developed and especially for developing countries include increasing the numbers of individuals who do not smoke, who eat healthy diets and who are physically active at levels that are health enhancing. In developing countries, deaths from chronic disease are projected to increase from 56% of all deaths in 2005 to 65% by 2030 (driven largely driven by deaths due to cardiovascular and coronary heart disease); in developed countries, however, the increase is only from 87.5 to 88.5%. The data on physical inactivity presented in this review were derived primarily from World Health Organization (WHO) publications and data warehouses. The prevalence of physical inactivity at less than the levels recommended for enhancing health is high; from 17 to 91% in developing countries and from 4 to 84% in developed countries. In developed countries, physical inactivity is associated with considerable economic burden, with 1.5-3.0% of total direct healthcare costs being accounted for by physical inactivity. Other than on some exciting work in Brazil, there is little information on the effectiveness and cost-effectiveness of physical activity-enhancement strategies in developing countries. The WHO has signaled a shift from the treatment of illness to promotion of health, with an emphasis on changing modifiable health-risk factors, including smoking, unhealthy diets and physical inactivity: the real question, especially for developing countries, is 'what is the future healthcare cost of not encouraging healthier lifestyles today?' PMID:18391637

  19. Site Energies of Active and Inactive Pheophytins in the Reaction Center of Photosystem II from Chlamydomonas Reinhardtii

    SciTech Connect

    Acharya, K.; Neupane, B.; Zazubovich, V.; Sayre, R. T.; Picorel, R.; Seibert, M.; Jankowiak, R.

    2012-03-29

    It is widely accepted that the primary electron acceptor in various Photosystem II (PSII) reaction center (RC) preparations is pheophytin {alpha} (Pheo {alpha}) within the D1 protein (Pheo{sub D1}), while Pheo{sub D2} (within the D2 protein) is photochemically inactive. The Pheo site energies, however, have remained elusive, due to inherent spectral congestion. While most researchers over the past two decades placed the Q{sub y}-states of Pheo{sub D1} and Pheo{sub D2} bands near 678-684 and 668-672 nm, respectively, recent modeling [Raszewski et al. Biophys. J. 2005, 88, 986-998; Cox et al. J. Phys. Chem. B 2009, 113, 12364-12374] of the electronic structure of the PSII RC reversed the assignment of the active and inactive Pheos, suggesting that the mean site energy of Pheo{sub D1} is near 672 nm, whereas Pheo{sub D2} ({approx}677.5 nm) and Chl{sub D1} ({approx}680 nm) have the lowest energies (i.e., the Pheo{sub D2}-dominated exciton is the lowest excited state). In contrast, chemical pigment exchange experiments on isolated RCs suggested that both pheophytins have their Q{sub y} absorption maxima at 676-680 nm [Germano et al. Biochemistry 2001, 40, 11472-11482; Germano et al. Biophys. J. 2004, 86, 1664-1672]. To provide more insight into the site energies of both Pheo{sub D1} and Pheo{sub D2} (including the corresponding Q{sub x} transitions, which are often claimed to be degenerate at 543 nm) and to attest that the above two assignments are most likely incorrect, we studied a large number of isolated RC preparations from spinach and wild-type Chlamydomonas reinhardtii (at different levels of intactness) as well as the Chlamydomonas reinhardtii mutant (D2-L209H), in which the active branch Pheo{sub D1} is genetically replaced with chlorophyll {alpha} (Chl {alpha}). We show that the Q{sub x}-/Q{sub y}-region site energies of Pheo{sub D1} and Pheo{sub D2} are {approx}545/680 nm and {approx}541.5/670 nm, respectively, in good agreement with our previous assignment

  20. Analysis by substituted cysteine scanning mutagenesis of the fourth transmembrane domain of the CXCR4 receptor in its inactive and active state.

    PubMed

    Boulais, Philip E; Escher, Emanuel; Leduc, Richard

    2013-02-15

    The chemokine SDF-1 (CXCL12) selectively binds to CXCR4, a member of the G protein-coupled receptor (GPCR) superfamily. In this study, we used the substituted-cysteine accessibility method (SCAM) to identify specific residues of the fourth transmembrane domain (TM4) that contribute to the formation of the binding pocket of CXCR4 in its inactive and active state. We successively substituted each residue from E179((4.68)) to K154((4.43)) with cysteine and expressed the mutants in COS-7 cells. Mutant receptors were then alkylated with methanethiosulfonate-ethylammonium (MTSEA), and binding inhibition was monitored using the CXCR4 antagonist FC131 [cyclo(-D-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)], which displays anti-HIV activity. MTSEA treatment resulted in a significant reduction of FC131 binding to D171C((4.60)) and P170C((4.59)). To assess TM4 accessibility in an active state of CXCR4, TM4 cysteine mutants were transposed within the constitutively active mutant N119S((3.35)). MTSEA treatment of TM4 mutants N119S-S178C((4.67)), N119S-V177C((4.66)) and N119S-I173C((4.62)) resulted in a significant reduction in FC131 binding. Protection assays using FC131 prior to MTSEA treatment significantly reduced the alkylation of all MTSEA-sensitive mutants. The accessibility of the D171C((4.60)) and P170C((4.59)) residues suggests that they are oriented towards a water-accessible area of the binding pocket of CXCR4. S178C((4.67)), V177C((4.66)) and I173C((4.62)) showed binding inhibition only in an N119S((3.35)) background. Taken together our results suggest that TM4 and ECL2 undergo conformational changes during CXCR4 activation and also demonstrate how TM4 is an important feature for the binding of anti-HIV compounds. PMID:23219524

  1. Uveitic angle closure glaucoma in a patient with inactive cytomegalovirus retinitis and immune recovery uveitis.

    PubMed

    Goldberg, Daniel E; Freeman, William R

    2002-01-01

    We report a case of uveitic acute angle closure glaucoma in a patient with acquired immunodeficiency syndrome (AIDS) associated with inactive cytomegalovirus retinitis and immune recovery vitritis. We conducted a long-term, follow-up examination of a 47-year-old male with AIDS and inactive cytomegalovirus retinitis caused by immune recovery on highly active antiretroviral therapy (HAART). We found vitritis and ultimate development of uveitic glaucoma in the postoperative periods following repair of retinal detachment and extracapsular cataract extraction with intraocular lens implant. An episode of acute angle closure secondary to posterior synechiae and iris bombé subsequently developed, requiring peripheral laser iridotomy. Immune recovery in the setting of inactive cytomegalovirus retinitis can result in intraocular inflammation severe enough to cause angle closure glaucoma and profound ocular morbidity. PMID:12358297

  2. Effect of acute exercise on some haematological parameters and neutrophil functions in active and inactive subjects.

    PubMed

    Benoni, G; Bellavite, P; Adami, A; Chirumbolo, S; Lippi, G; Brocco, G; Cuzzolin, L

    1995-01-01

    In this work we studied the possible effects of acute exercise on some haematological parameters and on some functions of neutrophils in seven active and six inactive subjects. Physical exercise (10 min on a cycle ergometer at a heart rate of 150 beats.min-1) induced a significant increase in total leucocyte, lymphocyte and neutrophil concentrations in active subjects; serum iron and ferritin concentrations were lower in active compared to inactive subjects. Cellular adhesion, bactericidal activity and superoxide anion production did not change after exercise, while we also observed some differences between active and inactive subjects before exercise. In particular, the neutrophils from active subjects showed a significantly higher percentage of adhesion, higher bactericidal activity and lower superoxide anion production. In conclusion, the training induced changes in some neutrophil functions, while acute exercise influenced, overall, leucocyte concentrations. PMID:7768243

  3. Discrimination of active and inactive sand from remote sensing - Kelso dunes, Mojave Desert, California

    NASA Technical Reports Server (NTRS)

    Paisley, Elizabeth C. I.; Lancaster, Nicholas; Gaddis, Lisa R.; Greeley, Ronald

    1991-01-01

    Landsat TM images, field data, and laboratoray reflectance spectra were examined for the Kelso dunes, Mojave Desert, California to assess the use of visible and near-infrared (VNIR) remote sensing data to discriminate aeolian sand populations on the basis of spectral brightness. Results show that areas of inactive sand have a larger percentage of dark, fine-grained materials compared to those composed of active sand, which contain less dark fines and a higher percentage of quartz sand-size grains. Both areas are spectrally distinct in the VNIR, suggesting that VNIR spectral data can be used to discriminate active and inactive sand populations in the Mojave Desert. Analysis of laboratory spectra was complicated by the presence of magnetite in the active sands, which decreases their laboratory reflectance values to those of inactive sands. For this application, comparison of TM and laboratory spectra suggests that less than 35 percent vegetation cover does not influence the TM spectra.

  4. Linking geology and microbiology: inactive pockmarks affect sediment microbial community structure.

    PubMed

    Haverkamp, Thomas H A; Hammer, Øyvind; Jakobsen, Kjetill S

    2014-01-01

    Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined what the microbial composition of inactive pockmarks is and if it shows a similar pattern as the macrofauna. The Norwegian Oslofjord contains many inactive pockmarks and they are well suited to study the influence of these geological features on the microbial community in the sediment. Here we present a detailed analysis of the microbial communities found in three inactive pockmarks and two control samples at two core depth intervals. The communities were analyzed using high-throughput amplicon sequencing of the 16S rRNA V3 region. Microbial communities of surface pockmark sediments were indistinguishable from communities found in the surrounding seabed. In contrast, pockmark communities at 40 cm sediment depth had a significantly different community structure from normal sediments at the same depth. Statistical analysis of chemical variables indicated significant differences in the concentrations of total carbon and non-particulate organic carbon between 40 cm pockmarks and reference sample sediments. We discuss these results in comparison with the taxonomic classification of the OTUs identified in our samples. Our results indicate that microbial communities at the sediment surface are affected by the water column, while the deeper (40 cm) sediment communities are affected by local conditions within the sediment. PMID:24475066

  5. The Association of Ambient Air Pollution and Physical Inactivity in the United States

    PubMed Central

    Roberts, Jennifer D.; Voss, Jameson D.; Knight, Brandon

    2014-01-01

    Background Physical inactivity, ambient air pollution and obesity are modifiable risk factors for non-communicable diseases, with the first accounting for 10% of premature deaths worldwide. Although community level interventions may target each simultaneously, research on the relationship between these risk factors is lacking. Objectives After comparing spatial interpolation methods to determine the best predictor for particulate matter (PM2.5; PM10) and ozone (O3) exposures throughout the U.S., we evaluated the cross-sectional association of ambient air pollution with leisure-time physical inactivity among adults. Methods In this cross-sectional study, we assessed leisure-time physical inactivity using individual self-reported survey data from the Centers for Disease Control and Prevention's 2011 Behavioral Risk Factor Surveillance System. These data were combined with county-level U.S. Environmental Protection Agency air pollution exposure estimates using two interpolation methods (Inverse Distance Weighting and Empirical Bayesian Kriging). Finally, we evaluated whether those exposed to higher levels of air pollution were less active by performing logistic regression, adjusting for demographic and behavioral risk factors, and after stratifying by body weight category. Results With Empirical Bayesian Kriging air pollution values, we estimated a statistically significant 16–35% relative increase in the odds of leisure-time physical inactivity per exposure class increase of PM2.5 in the fully adjusted model across the normal weight respondents (p-value<0.0001). Evidence suggested a relationship between the increasing dose of PM2.5 exposure and the increasing odds of physical inactivity. Conclusions In a nationally representative, cross-sectional sample, increased community level air pollution is associated with reduced leisure-time physical activity particularly among the normal weight. Although our design precludes a causal inference, these results provide

  6. Linking Geology and Microbiology: Inactive Pockmarks Affect Sediment Microbial Community Structure

    PubMed Central

    Haverkamp, Thomas H. A.; Hammer, Øyvind; Jakobsen, Kjetill S.

    2014-01-01

    Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined what the microbial composition of inactive pockmarks is and if it shows a similar pattern as the macrofauna. The Norwegian Oslofjord contains many inactive pockmarks and they are well suited to study the influence of these geological features on the microbial community in the sediment. Here we present a detailed analysis of the microbial communities found in three inactive pockmarks and two control samples at two core depth intervals. The communities were analyzed using high-throughput amplicon sequencing of the 16S rRNA V3 region. Microbial communities of surface pockmark sediments were indistinguishable from communities found in the surrounding seabed. In contrast, pockmark communities at 40 cm sediment depth had a significantly different community structure from normal sediments at the same depth. Statistical analysis of chemical variables indicated significant differences in the concentrations of total carbon and non-particulate organic carbon between 40 cm pockmarks and reference sample sediments. We discuss these results in comparison with the taxonomic classification of the OTUs identified in our samples. Our results indicate that microbial communities at the sediment surface are affected by the water column, while the deeper (40 cm) sediment communities are affected by local conditions within the sediment. PMID:24475066

  7. Modifiers of mutant huntingtin aggregation

    PubMed Central

    Teuling, Eva; Bourgonje, Annika; Veenje, Sven; Thijssen, Karen; de Boer, Jelle; van der Velde, Joeri; Swertz, Morris; Nollen, Ellen

    2011-01-01

    Protein aggregation is a common hallmark of a number of age-related neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and polyglutamine-expansion disorders such as Huntington’s disease, but how aggregation-prone proteins lead to pathology is not known. Using a genome-wide RNAi screen in a C. elegans-model for polyglutamine aggregation, we previously identified 186 genes that suppress aggregation. Using an RNAi screen for human orthologs of these genes, we here present 26 human genes that suppress aggregation of mutant huntingtin in a human cell line. Among these are genes that have not been previously linked to mutant huntingtin aggregation. They include those encoding eukaryotic translation initiation, elongation and translation factors, and genes that have been previously associated with other neurodegenerative diseases, like the ATP-ase family gene 3-like 2 (AFG3L2) and ubiquitin-like modifier activating enzyme 1 (UBA1). Unravelling the role of these genes will broaden our understanding of the pathogenesis of Huntington’s disease. PMID:21915392

  8. Molecular Dynamics Analysis of Binding of Kinase Inhibitors to WT EGFR and the T790M Mutant.

    PubMed

    Park, Jiyong; McDonald, Joseph J; Petter, Russell C; Houk, K N

    2016-04-12

    Epidermal growth factor receptor (EGFR) inhibitors interrupt EGFR-dependent cellular signaling pathways that lead to accelerated tumor growth and proliferation. Mutation of a threonine in the inhibitor binding pocket, known as the "gatekeeper", to methionine (T790M) confers acquired resistance to several EGFR-selective inhibitors. We studied interactions between EGFR inhibitors and the gatekeeper residues of the target protein. Thermodynamic integration (TI) with Amber14 indicates that the binding energies of gefitinib and AEE788 to the active state of the T790M mutant EGFR is 3 kcal/mol higher than to the wild type (WT), whereas ATP binding energy to the mutant is similar to the WT. Using metadynamics MD simulations with NAMD v2.9, the conformational equilibrium between the inactive resting state and the catalytically competent activate state was determined for the WT EGFR. When combined with the results obtained by Sutto and Gervasio, our simulations showed that the T790M point mutation lowers the free energy of the active state by 5 kcal/mol relative to the inactive state of the enzyme. Relative to the WT, the T790M mutant binds gefitinib more strongly. The T790M mutation is nevertheless resistant due to its increased binding of ATP. By contrast, the binding of AEE788 to the active state causes a conformational change in the αC-helix adjacent to the inhibitor binding pocket, that results in a 2 kcal/mol energy penalty. The energy penalty explains why the binding of AEE788 to the T790M mutant is unfavorable relative to binding to WT EGFR. These results establish the role of the gatekeeper mutation on inhibitor selectivity. Additional molecular dynamics (MD) simulations, TI, and metadynamics MD simulations reveal the origins of the changes in binding energy of WT and mutants. PMID:27010480

  9. Accumulation of B1-like B cells in transgenic mice over-expressing catalytically inactive RAG1 in the periphery

    PubMed Central

    Hassaballa, Ashraf E; Palmer, Victoria L; Anderson, Dirk K; Kassmeier, Michele D; Nganga, Vincent K; Parks, Kevin W; Volkmer, Dustin L; Perry, Greg A; Swanson, Patrick C

    2011-01-01

    During their development, B lymphocytes undergo V(D)J recombination events and selection processes that, if successfully completed, produce mature B cells expressing a non-self-reactive B-cell receptor (BCR). Primary V(D)J rearrangements yield self-reactive B cells at high frequency, triggering attempts to remove, silence, or reprogramme them through deletion, anergy induction, or secondary V(D)J recombination (receptor editing), respectively. In principle, expressing a catalytically inactive V(D)J recombinase during a developmental stage in which V(D)J rearrangement is initiated may impair this process. To test this idea, we generated transgenic mice expressing a RAG1 active site mutant (dnRAG1 mice); RAG1 transcript was elevated in splenic, but not bone marrow, B cells in dnRAG1 mice relative to wild-type mice. The dnRAG1 mice accumulate splenic B cells with a B1-like phenotype that exhibit defects in B-cell activation, and are clonally diverse, yet repertoire restricted with a bias toward Jκ1 gene segment usage. The dnRAG1 mice show evidence of impaired B-cell development at the immature-to-mature transition, immunoglobulin deficiency, and poorer immune responses to thymus-independent antigens. Interestingly, dnRAG1 mice expressing the anti-dsDNA 3H9H56R heavy chain fail to accumulate splenic B1-like cells, yet retain peritoneal B1 cells. Instead, these mice show an expanded marginal zone compartment, but no difference is detected in the frequency of heavy chain gene replacement. Taken together, these data suggest a model in which dnRAG1 expression impairs secondary V(D)J recombination. As a result, selection and/or differentiation processes are altered in a way that promotes expansion of B1-like B cells in the spleen. PMID:22044391

  10. Allele Specific p53 Mutant Reactivation

    PubMed Central

    Yu, Xin; Vazquez, Alexei; Levine, Arnold J.; Carpizo, Darren R.

    2012-01-01

    Summary Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. PMID:22624712

  11. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  12. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  13. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  14. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  15. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... nonpulmonary tuberculosis in effect on August 19, 1968. 4.89 Section 4.89 Pensions, Bonuses, and Veterans... tuberculosis in effect on August 19, 1968. Public Law 90-493 repealed section 356 of title 38, United States Code which provided graduated ratings for inactive tuberculosis. The repealed section, however,...

  16. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... nonpulmonary tuberculosis in effect on August 19, 1968. 4.89 Section 4.89 Pensions, Bonuses, and Veterans... tuberculosis in effect on August 19, 1968. Public Law 90-493 repealed section 356 of title 38, United States Code which provided graduated ratings for inactive tuberculosis. The repealed section, however,...

  17. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... nonpulmonary tuberculosis in effect on August 19, 1968. 4.89 Section 4.89 Pensions, Bonuses, and Veterans... tuberculosis in effect on August 19, 1968. Public Law 90-493 repealed section 356 of title 38, United States Code which provided graduated ratings for inactive tuberculosis. The repealed section, however,...

  18. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  19. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  20. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  1. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... nonpulmonary tuberculosis in effect on August 19, 1968. 4.89 Section 4.89 Pensions, Bonuses, and Veterans... tuberculosis in effect on August 19, 1968. Public Law 90-493 repealed section 356 of title 38, United States Code which provided graduated ratings for inactive tuberculosis. The repealed section, however,...

  2. When Physical Activity Participation Promotes Inactivity: Negative Experiences of Spanish Adolescents in Physical Education and Sport

    ERIC Educational Resources Information Center

    Beltran-Carrillo, Vicente J.; Devis-Devis, Jose; Peiro-Velert, Carmen; Brown, David H. K.

    2012-01-01

    This article analyses negative experiences in physical education and sport reported during qualitative interviews of a group of inactive adolescent Spanish boys and girls. The purpose of this analysis is twofold. First and most important, it seeks to give voice to these young people reporting negative experiences and connect them to contexts of…

  3. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  4. Exploring Socio-Ecological Factors Influencing Active and Inactive Spanish Students in Years 12 and 13

    ERIC Educational Resources Information Center

    Devís-Devís, José; Beltrán-Carrillo, Vicente J.; Peiró-Velert, Carmen

    2015-01-01

    This paper explores socio-ecological factors and their interplay that emerge from a qualitative study and influence adolescents' physical activity and sport participation. A total of 13 boys and 7 girls active and inactive adolescents, from years 12 and 13 and different types of school (state and private), participated in semi-structured…

  5. Emotional Outlook on Life Predicts Increases in Physical Activity among Initially Inactive Men

    ERIC Educational Resources Information Center

    Baruth, Meghan; Lee, Duck-Chul; Sui, Xuemei; Church, Timothy S.; Marcus, Bess H.; Wilcox, Sara; Blair, Steven N.

    2011-01-01

    This study examined the relationship between emotional outlook on life and change in physical activity among inactive adults in the Aerobics Center Longitudinal Study. A total of 2,132 sedentary adults completed a baseline medical examination and returned for a follow-up examination at least 6 months later. Participants self-reported physical…

  6. 17 CFR 210.3-11 - Financial statements of an inactive registrant.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Financial statements of an... COMMISSION FORM AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933, SECURITIES... Financial Statements § 210.3-11 Financial statements of an inactive registrant. If a registrant is...

  7. Past-Year Sexual Inactivity among Older Married Persons and Their Partners

    ERIC Educational Resources Information Center

    Karraker, Amelia; DeLamater, John

    2013-01-01

    Family scholars have focused on the onset of sexual activity early in the life course, but little is known about the cessation of sexual activity in relationships in later life. We use event-history analysis techniques and logistic regression to identify the correlates of sexual inactivity among older married men and women. We analyze data for…

  8. Physical inactivity and obesity: Using a novel environmental quality measure to control confounding

    EPA Science Inventory

    Physical inactivity is well-established as a contributor to obesity prevalence in the US. Many aspects of the ambient environment (e.g., air pollution, food deserts, neighborhood socioeconomics) have also been associated with obesity. Yet, controlling for the overall ambient envi...

  9. Evaluating Equity: A Framework for Understanding Action and Inaction on Social Justice Issues

    ERIC Educational Resources Information Center

    Opfer, V. Darleen

    2006-01-01

    This article relies on a case study of a policy evaluation to illustrate how issues of social justice arise for action or inaction in a political environment. The article uses the case study to show that social justice issue formation is shaped by the personal beliefs of the actors, the prevailing political culture, the evolutionary path of the…

  10. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  11. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  12. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  13. 9 CFR 105.4 - Termination of licenses and permits for inactivity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Termination of licenses and permits for inactivity. 105.4 Section 105.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND...

  14. Effects of inactivity on myosin heavy chain composition and size of rat soleus fibers

    NASA Technical Reports Server (NTRS)

    Grossman, E. J.; Roy, R. R.; Talmadge, R. J.; Zhong, H.; Edgerton, V. R.

    1998-01-01

    Myosin heavy chain (MHC) and fiber size properties of the adult rat soleus were determined after 4-60 days of complete inactivity, i.e., lumbar spinal cord isolation. Soleus atrophy was rapid and progressive, i.e., 25% and 64% decrease in weight and 33% and 75% decrease in fiber size after 4 and 60 days of inactivity, respectively. Changes in MHC occurred at a slower rate than the atrophic response. After 15 days there was de novo expression of type IIx MHC (approximately 10%). By 60 days, type IIx MHC accounted for 33% of the total MHC content, and 7% of the fibers contained only type IIx MHC. The relative amount of type I MHC was reduced from 93% in control to 49% after 60 days of inactivity. Therefore, the effects of 60 days of inactivity suggest that during this time period at least 75% of fiber size and approximately 40% of type I MHC composition of the adult rat soleus can be attributed to activation-related events.

  15. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968. 4.89 Section 4.89 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders and...

  16. Abnormal lignin in a loblolly pine mutant

    SciTech Connect

    Ralph, J.; MacKay, J.J.; Hatfield, R.D.

    1997-07-11

    Novel lignin is formed in a mutant loblolly pine (Pinus taeda L.) severely depleted in cinnamyl alcohol dehydrogenase (E.C. 1.1.1.195), which converts coniferaldehyde to coniferyl alcohol, the primary lignin precursor in pines. Dihydroconiferyl alcohol, a monomer not normally associated with the lignin biosynthetic pathway, is the major component of the mutant`s lignin, accounting for {approximately}30 percent (versus {approximately}3 percent in normal pine) of the units. The level of aldehydes, including new 2-methoxybenzaldehydes, is also increased. The mutant pines grew normally indicating that, even within a species, extensive variations in lignin composition need not disrupt the essential functions of lignin.

  17. Identifying representative drug resistant mutants of HIV

    PubMed Central

    2015-01-01

    Background Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. Results In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. Conclusion This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID:26678327

  18. Why are Jupiter-family comets active and asteroids in cometary-like orbits inactive?. How hydrostatic compression leads to inactivity

    NASA Astrophysics Data System (ADS)

    Gundlach, B.; Blum, J.

    2016-05-01

    Context. Surveys in the visible and near-infrared spectral range have revealed the presence of low-albedo asteroids in cometary-like orbits (ACOs). In contrast to Jupiter-family comets (JFCs), ACOs are inactive, but possess similar orbital parameters. Aims: In this work, we discuss why ACOs are inactive, whereas JFCs show gas-driven dust activity, although both belong to the same class of primitive solar system bodies. Methods: We hypothesize that ACOs and JFCs have formed under the same physical conditions, namely by the gravitational collapse of ensembles of ice and dust aggregates. We use the memory effect of dust-aggregate layers under gravitational compression to discuss under which conditions the gas-driven dust activity of these bodies is possible. Results: Owing to their smaller sizes, JFCs can sustain gas-driven dust activity much longer than the bigger ACOs, whose sub-surface regions possess an increased tensile strength, due to gravitational compression of the material. The increased tensile strength leads to the passivation against dust activity after a relatively short time of activity. Conclusions: The gravitational-collapse model of the formation of planetesimals, together with the gravitational compression of the sub-surface material simultaneously, explains the inactivity of ACOs and the gas-driven dust activity of JFCs. Their initially larger sizes means that ACOs possess a higher tensile strength of their sub-surface material, which leads to a faster termination of gas-driven dust activity. Most objects with radii larger than 2 km have already lost their activity due to former gravitational compression of their current surface material.

  19. Analysis of Mutant SOD1 Electrophoretic Mobility by Blue Native Gel Electrophoresis; Evidence for Soluble Multimeric Assemblies

    PubMed Central

    Brown, Hilda H.; Borchelt, David R.

    2014-01-01

    Mutations in superoxide dismutase 1 (SOD1) cause familial forms of amyotrophic lateral sclerosis (fALS). Disease causing mutations have diverse consequences on the activity and half-life of the protein, ranging from complete inactivity and short half-life to full activity and long-half-life. Uniformly, disease causing mutations induce the protein to misfold and aggregate and such aggregation tendencies are readily visualized by over-expression of the proteins in cultured cells. In the present study we have investigated the potential of using immunoblotting of proteins separated by Blue-Native gel electrophoresis (BNGE) as a means to identify soluble multimeric forms of mutant protein. We find that over-expressed wild-type human SOD1 (hSOD1) is generally not prone to form soluble high molecular weight entities that can be separated by BNGE. For ALS mutant SOD1, we observe that for all mutants examined (A4V, G37R, G85R, G93A, and L126Z), immunoblots of BN-gels separating protein solubilized by digitonin demonstrated varied amounts of high molecular weight immunoreactive entities. These entities lacked reactivity to ubiquitin and were partially dissociated by reducing agents. With the exception of the G93A mutant, these entities were not reactive to the C4F6 conformational antibody. Collectively, these data demonstrate that BNGE can be used to assess the formation of soluble multimeric assemblies of mutant SOD1. PMID:25121776

  20. The Impact of Smoking on Airflow Limitation in Subjects with History of Asthma and Inactive Tuberculosis

    PubMed Central

    Kim, Hyun Jung; Baek, Seunghee; Kim, Hee Jin; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2015-01-01

    Background Although smoking is the most important and modifiable cause of chronic obstructive pulmonary disease (COPD), other risk factors including asthma and tuberculosis (TB) are also associated. It is common for COPD patients to have more than one of these risk factors. The aims of this study were to determine the prevalence of airflow limitation (FEV1/FVC<0.7) according to the risk factors and to investigate their impact and interaction in airflow limitation. Methods From the Korean National Health and Nutrition Examination Survey between 2008 and 2012, we analyzed participants over 40 years of age by spirometry, chest radiograph and questionnaire about asthma and smoking history. Results Of 12,631 participants, 1,548 (12.3%) had airflow limitation. The prevalence of airflow limitation in smokers (≥10 pack-year), asthmatics, and those with inactive TB was 23.9%, 32.1%, and 33.6%. The prevalence increased with the number of risk factors: 86.1% had airflow limitation if they had all three risk factors. Impacts of inactive TB and asthma on airflow limitation were equivalent to 47 and 69 pack-years of smoking, respectively. Airflow limitation resulted from lower levels of smoking in those with inactive TB and asthma. A potential interaction between smoking and inactive tuberculosis in the development of airflow limitation was identified (p = 0.054). Conclusions Asthma and inactive TB lesions increase susceptibility to smoking in the development of airflow limitation. People with these risk factors should be seen as a major target population for anti-smoking campaigns to prevent COPD. PMID:25915938

  1. The association of current and sustained area-based adverse socioeconomic environment with physical inactivity.

    PubMed

    Pascual, Cruz; Regidor, Enrique; Astasio, Paloma; Ortega, Paloma; Navarro, Pedro; Domínguez, Vicente

    2007-08-01

    This paper evaluates the association between socioeconomic environment in the province of residence and physical inactivity, using measures of current and sustained area-based adverse socioeconomic environment. The analysis included 19,324 individuals representative of the Spanish non-institutionalised population aged 16-74 years. The measure of association estimated was the prevalence odds ratio for physical inactivity by current gross domestic product per capita (GDPpc) and current Gini coefficient, and by number of times each province has had a low GDPpc and number of times each province has had a high Gini coefficient in the last two decades. After adjusting for age, individual socioeconomic characteristics, and number of sports facilities per 1,000 population, the odds ratio for physical inactivity in residents of provinces with the lowest current GDPpc versus those with the highest was 1.64 in men and 2.01 in women. The odds ratio in residents of provinces that had always been among those with the lowest GDPpc versus residents in provinces that had never been among those with lowest GDPpc was 1.54 in men and 1.91 in women. Neither the current Gini coefficient nor the indicator that reflects sustained high Gini coefficient were associated with physical inactivity. These findings show that physical inactivity is associated with current socioeconomic context and with the duration of exposure of the area of residence to adverse socioeconomic circumstances when the indicators of socioeconomic environment are based on GDPpc, but not on income inequality. Also, this association is not explained by individual socioeconomic characteristics or the number of sports facilities. PMID:17466424

  2. Impact of Physical Inactivity on Mortality in Patients With Heart Failure.

    PubMed

    Doukky, Rami; Mangla, Ashvarya; Ibrahim, Zeina; Poulin, Marie-France; Avery, Elizabeth; Collado, Fareed M; Kaplan, Jonathan; Richardson, DeJuran; Powell, Lynda H

    2016-04-01

    The impact of physical inactivity on heart failure (HF) mortality is unclear. We analyzed data from the HF Adherence and Retention Trial (HART) which enrolled 902 patients with New York Heart Association class II/III HF, with preserved or reduced ejection fraction, who were followed for 36 months. On the basis of mean self-reported weekly exercise duration, patients were classified into inactive (0 min/week) and active (≥1 min/week) groups and then propensity score matched according to 34 baseline covariates in 1:2 ratio. Sedentary activity was determined according to self-reported daily television screen time (<2, 2 to 4, >4 h/day). The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. There were 196 inactive patients, of whom 171 were propensity matched to 342 active patients. Physical inactivity was associated with greater risk of all-cause death (hazard ratio [HR] 2.01, confidence interval [CI] 1.47 to 3.00; p <0.001) and cardiac death (HR 2.01, CI 1.28 to 3.17; p = 0.002) but no significant difference in HF hospitalization (p = 0.548). Modest exercise (1 to 89 min/week) was associated with a significant reduction in the rate of death (p = 0.003) and cardiac death (p = 0.050). Independent of exercise duration and baseline covariates, television screen time (>4 vs <2 h/day) was associated with all-cause death (HR 1.65, CI 1.10 to 2.48; p = 0.016; incremental chi-square = 6.05; p = 0.049). In conclusion, in patients with symptomatic chronic HF, physical inactivity is associated with higher all-cause and cardiac mortality. Failure to exercise and television screen time are additive in their effects on mortality. Even modest exercise was associated with survival benefit. PMID:26853954

  3. Body image emotions, perceptions, and cognitions distinguish physically active and inactive smokers

    PubMed Central

    Contreras, Gisèle A.; Sabiston, Catherine M.; O'Loughlin, Erin K.; Bélanger, Mathieu; O'Loughlin, Jennifer

    2015-01-01

    Objectives To determine if body image emotions (body-related shame and guilt, weight-related stress), perceptions (self-perceived overweight), or cognitions (trying to change weight) differ between adolescents characterized by smoking and physical activity (PA) behavior. Methods Data for this cross-sectional analysis were collected in 2010–11 and were available for 1017 participants (mean (SD) age = 16.8 (0.5) years). Participants were categorized according to smoking and PA status into four groups: inactive smokers, inactive non-smokers, active smokers and active non-smokers. Associations between body image emotions, perceptions and cognitions, and group membership were estimated in multinomial logistic regression. Results Participants who reported body-related shame were less likely (OR (95% CI) = 0.52 (0.29–0.94)) to be in the active smoker group than the inactive smoker group; those who reported body-related guilt and those trying to gain weight were more likely (2.14 (1.32–3.48) and 2.49 (1.22–5.08), respectively) to be in the active smoker group than the inactive smoker group; those who were stressed about weight and those perceiving themselves as overweight were less likely to be in the active non-smoker group than the inactive smoker group (0.79 (0.64–0.97) and 0.41 (0.19–0.89), respectively). Conclusion Body image emotions and cognitions differentiated the active smoker group from the other three groups. PMID:26844062

  4. 42 CFR 407.32 - Prejudice to enrollment rights because of Federal Government misrepresentation, inaction, or error.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Government misrepresentation, inaction, or error. 407.32 Section 407.32 Public Health CENTERS FOR MEDICARE... enrollment rights because of Federal Government misrepresentation, inaction, or error. If an individual's enrollment or nonenrollment in SMI is unintentional, inadvertent, or erroneous because of the...

  5. Places where preschoolers are (in)active: An observational study on Latino preschoolers and their parents using objective measures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To combat the disproportionately higher risk of childhood obesity in Latino preschool-aged children, multilevel interventions targeting physical (in)activity are needed. These require the identification of environmental and psychosocial determinants of physical (in)activity for this ethnic group. Th...

  6. Urban-Rural Differences in Overweight Status and Physical Inactivity among US Children Aged 10-17 Years

    ERIC Educational Resources Information Center

    Liu, Jihong; Bennett, Kevin J.; Harun, Nusrat; Probst, Janice C.

    2008-01-01

    Context: Few studies have examined the prevalence of overweight status and physical inactivity among children and adolescents living in rural America. Purpose: We examined urban and rural differences in the prevalence of overweight status and physical inactivity among US children. Methods: Data were drawn from the 2003 National Survey of…

  7. Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2

    PubMed Central

    Andreotti, Giuseppina; Monti, Maria Chiara; Citro, Valentina; Cubellis, Maria Vittoria

    2015-01-01

    The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces the protein found in patients, has the same activity of wild type/R141H, which reproduces the protein found in healthy carriers. On the other hand the stability of R141H/F119L appears to be reduced both in vitro and in vivo. These findings suggest that a therapy designed to enhance protein stability such as those based on pharmacological chaperones or modulation of proteostasis could be beneficial for PMM2-CDG patients carrying R141H/F119L genotype as well as for other genotypes where protein stability rather than specific activity is affected by mutations. PMID:26488408

  8. Regulation of Mutant p53 Protein Expression

    PubMed Central

    Vijayakumaran, Reshma; Tan, Kah Hin; Miranda, Panimaya Jeffreena; Haupt, Sue; Haupt, Ygal

    2015-01-01

    For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be explained in mutant p53-expressing cells by the lack of an auto-regulatory loop with Mdm2 and other negative regulators, which are pivotal for wt p53 regulation. Further, additional protective mechanisms are acquired by mutant p53, largely mediated by the co-chaperones and their paralogs, the stress-induced heat shock proteins. Consequently, mutant p53 is accumulated in cancer cells in response to chronic stress and this accumulation is critical for its oncogenic gain of functions (GOF). Building on the extensive knowledge regarding wt p53, the regulation of mutant p53 is unraveling. In this review, we describe the current understanding on the major levels at which mutant p53 is regulated. These include the regulation of p53 protein levels by microRNA and by enzymes controlling p53 proteasomal degradation. PMID:26734569

  9. Uncaging Mutants: Moving From Menageries to Menages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The thousands of mutants of maize are a remarkable resource for study of plant physiology, phylogeny, cell biology, biochemistry, development, and molecular biology. Mutants are most often applied in research studies as "members of collections" rather than as select families of members relevant to ...

  10. Nebulin binding impedes mutant desmin filament assembly

    PubMed Central

    Baker, Laura K.; Gillis, David C.; Sharma, Sarika; Ambrus, Andy; Herrmann, Harald; Conover, Gloria M.

    2013-01-01

    Desmin intermediate filaments (DIFs) form an intricate meshwork that organizes myofibers within striated muscle cells. The mechanisms that regulate the association of desmin to sarcomeres and their role in desminopathy are incompletely understood. Here we compare the effect nebulin binding has on the assembly kinetics of desmin and three desminopathy-causing mutant desmin variants carrying mutations in the head, rod, or tail domains of desmin (S46F, E245D, and T453I). These mutants were chosen because the mutated residues are located within the nebulin-binding regions of desmin. We discovered that, although nebulin M160–164 bound to both desmin tetrameric complexes and mature filaments, all three mutants exhibited significantly delayed filament assembly kinetics when bound to nebulin. Correspondingly, all three mutants displayed enhanced binding affinities and capacities for nebulin relative to wild-type desmin. Electron micrographs showed that nebulin associates with elongated normal and mutant DIFs assembled in vitro. Moreover, we measured significantly delayed dynamics for the mutant desmin E245D relative to wild-type desmin in fluorescence recovery after photobleaching in live-cell imaging experiments. We propose a mechanism by which mutant desmin slows desmin remodeling in myocytes by retaining nebulin near the Z-discs. On the basis of these data, we suggest that for some filament-forming desmin mutants, the molecular etiology of desminopathy results from subtle deficiencies in their association with nebulin, a major actin-binding filament protein of striated muscle. PMID:23615443

  11. Mutants of thermotaxis in Dictyostelium discoideum

    SciTech Connect

    Schneider, M.J.; Fontana, D.R.; Poff, K.L.

    1982-08-01

    Amoebae of Dictyostelium discoideum, strain HL50 were mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine, cloned, allowed to form pseudoplasmodia and screened for aberrant positive and negative thermotaxis. Three types of mutants were found. Mutant HO428 exhibits only positive thermotaxis over the entire temperature range (no negative thermotaxis). HO596 and HO813 exhibit weakened positive thermotaxis and normal negative thermotaxis. The weakened positive thermotactic response results in a shift toward warmer temperatures in the transition temperature from negative to positive thermotaxis. Mutant HO209 exhibits weakened positive and negative thermotactic responses and has a transition temperature similar to the 'wild type' (HL50).The two types of mutants represented by HO428, HO596 and HO813 support the model that positive and negative thermotaxis have separate pathways for temperature sensing. The type of mutants which contains HO209 suggests that those two pathways converge at some point before the response.

  12. Hypermutation of the Inactive X Chromosome Is a Frequent Event in Cancer

    PubMed Central

    Jäger, Natalie; Schlesner, Matthias; Jones, David T.W.; Raffel, Simon; Mallm, Jan-Philipp; Junge, Kristin M.; Weichenhan, Dieter; Bauer, Tobias; Ishaque, Naveed; Kool, Marcel; Northcott, Paul A.; Korshunov, Andrey; Drews, Ruben M.; Koster, Jan; Versteeg, Rogier; Richter, Julia; Hummel, Michael; Mack, Stephen C.; Taylor, Michael D.; Witt, Hendrik; Swartman, Benedict; Schulte-Bockholt, Dietrich; Sultan, Marc; Yaspo, Marie-Laure; Lehrach, Hans; Hutter, Barbara; Brors, Benedikt; Wolf, Stephan; Plass, Christoph; Siebert, Reiner; Trumpp, Andreas; Rippe, Karsten; Lehmann, Irina; Lichter, Peter; Pfister, Stefan M.; Eils, Roland

    2013-01-01

    Summary Mutation is a fundamental process in tumorigenesis. However, the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. Here, we performed a cross-cancer comparison of 402 whole genomes comprising a diverse set of childhood and adult tumors, including both solid and hematopoietic malignancies. Surprisingly, we found that the inactive X chromosome of many female cancer genomes accumulates on average twice and up to four times as many somatic mutations per megabase, as compared to the individual autosomes. Whole-genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals and a premalignant myelodysplastic syndrome (MDS) sample revealed no X chromosome hypermutation. Our data suggest that hypermutation of the inactive X chromosome is an early and frequent feature of tumorigenesis resulting from DNA replication stress in aberrantly proliferating cells. PMID:24139898

  13. The effects of exergaming on physical activity among inactive children in a physical education classroom.

    PubMed

    Fogel, Victoria A; Miltenberger, Raymond G; Graves, Rachel; Koehler, Shannon

    2010-01-01

    Childhood obesity, which is due in part to lack of physical activity, is a serious concern that requires the attention of the behavioral community. Although excessive video game play has been noted in the literature as a contributor to childhood obesity, newer video gaming technology, called exergaming, has been designed to capitalize on the reinforcing effects of video games to increase physical activity in children. This study evaluated the effects of exergaming on physical activity among 4 inactive children in a physical education (PE) classroom. Results showed that exergaming produced substantially more minutes of physical activity and more minutes of opportunity to engage in physical activity than did the standard PE program. In addition, exergaming was socially acceptable to both the students and the PE teacher. Exergaming appears to hold promise as a method for increasing physical activity among inactive children and might be a possible intervention for childhood obesity. PMID:21541146

  14. [Relationships between temperature change and microbial amount in inactive ice wedges in Yitulihe, Northeast China].

    PubMed

    Yang, Si-Zhong; Jin, Hui-Jun; Wen, Xi; Luo, Dong-Liang; Yu, Shao-Peng

    2009-11-01

    Ice-wedge is an indicator of paleoclimate change. The delta18 O concentration in different layers could reflect the change of paleotemperature during ice-wedge growth. In the late 1980s, inactive ice wedges were found in Yitulihe, Northeast China, which were the south-most ones so far and were important in climatic and environmental research. In this paper, the delta18 O concentration and microbial number in the inactive ice-wedges were analyzed by using stable isotope, fluorescence microscopy counting, and flow cytometer (FCM). During the ice-wedge growth in Yitulihe area, there were three short-term paleotemperature fluctuation, and three times of fluctuation in microbial amount in different ice-wedge layer. Correlation analysis indicated that there was a converging relationship between the temperature change and microbial amount in the ice-wedges. The lower the temperature when ice-wedge layer formed, the less the microbes survived in the layer. PMID:20136017

  15. Moyamoya syndrome occurred in a girl with an inactive systemic lupus erythematosus

    PubMed Central

    Lee, Yun-Jin; Yeon, Gyu Min; Nam, Sang Ook

    2013-01-01

    We report the case of a 17-year-old Korean girl with systemic lupus erythematosus (SLE) who presented with sudden weakness of the right-sided extremities and dysarthria. Oral prednisolone was being taken to control SLE. Results of clinical and laboratory examinations did not show any evidence of antiphospholipid syndrome or thromboembolic disease nor SLE activity. Cerebral angiography showed stenosis of the left internal carotid artery and right anterior cerebral artery with accompanying collateral circulation (moyamoya vessels). After the patient underwent bypass surgery on the left side, she recovered from the neurological problems and did not experience any additional ischemic attack during the 14-month follow-up period. This case represents an unusual association between moyamoya syndrome and inactive SLE (inactive for a relatively long interval of 2 years) in a young girl. PMID:24416051

  16. Dynamic characteristics of heat exchanger tubes vibrating in a tube support plate inactive mode

    SciTech Connect

    Jendrzejczyk, J.A.

    1984-06-01

    Tubes in shell-and-tube heat exchangers, including nuclear plant steam generators, derive their support from longitudinally positioned tube support plates (TSPs). Typically there is a clearance between the tube and TSP hole. Depending on design and fabrication tolerances, the tube may or may not contract all of the TSPs. Noncontact results in an inactive TSP which can lead to detrimental flow induced tube vibrations under certain conditions dependent on the resulting tube-TSP interaction dynamics and the fluid excitation forces. The purpose of this study is to investigate the tube-TSP interaction dynamics. Results of an experimental study of damping and natural frequency as functions of tube-TSP diametral clearance and TSP thickness are reported. Calculated values of damping ratio and frequency of a tube vibrating within an inactive TSP are also presented together with a comparison of calculated and experimental quantities.

  17. Dynamic characteristics of heat exchanger tubes vibrating in a tube support plate inactive mode

    SciTech Connect

    Jendrzejczyk, J.A.

    1985-01-01

    Tubes in shell-and-tube heat exchangers, including nuclear plant steam generators, derive their support from longitudinally positioned tube support plates (TSPs). Typically there is a clearance between the tube and TSP hole. Depending on design and fabrication tolerances, the tube may or may not contact all of the TSPs. Noncontact results in an inactive TSP which can lead to detrimental flow induced tube vibrations under certain conditions dependent on the resulting tube-TSP interaction dynamics and the fluid excitation forces. The purpose of this study is to investigate the tube-TSP interaction dynamics. Results of an experimental study of damping and natural frequency as functions of tube-TSP diametral clearance and TSP thickness are reported. Calculated values of damping ratio and frequency of a tube vibrating within an inactive TSP are also presented together with a comparison of calculated and experimetnal quantities.

  18. Revegetation and rock cover for stabilization of inactive uranium mill tailings disposal sites. Final report

    SciTech Connect

    Beedlow, P.A.

    1984-05-01

    Guidelines for using vegetation and rock to protect inactive uranium mill tailings from erosion were developed by Pacific Northwest Laboratory as part of the Department of Energy's Uranium Mill Tailings Remedial Action Project (UMTRAP) Technology Development program. Information on soils, climate, and vegetation were collected for 20 inactive tailings sites in the western United States. Sites were grouped according to similarities in climate and vegetation. Soil loss for those sites was characterized using the Universal Soil Loss Equation. Test plots were used to evaluate (1) the interaction between vegetation and sealant barrier systems and (2) the effects of surface rock on soil water and vegetation. Lysimeter and simulation studies were used to direct and support field experiments. 49 references, 17 figures, 16 tables.

  19. Investigation of the organic matter in inactive nuclear tank liquids. Environmental Restoration Program

    SciTech Connect

    Schenley, R.L.; Griest, W.H.

    1990-08-01

    Environmental Protection Agency (EPA) methodology for regulatory organics fails to account for the organic matter that is suggested by total organic carbon (TOC) analysis in the Oak Ridge National Laboratory (ORNL) inactive nuclear waste-tank liquids and sludges. Identification and measurement of the total organics are needed to select appropriate waste treatment technologies. An initial investigation was made of the nature of the organics in several waste-tank liquids. This report details the analysis of ORNL wastes.

  20. Redox potential tuning by redox-inactive cations in nature's water oxidizing catalyst and synthetic analogues.

    PubMed

    Krewald, Vera; Neese, Frank; Pantazis, Dimitrios A

    2016-04-20

    The redox potential of synthetic oligonuclear transition metal complexes has been shown to correlate with the Lewis acidity of a redox-inactive cation connected to the redox-active transition metals of the cluster via oxo or hydroxo bridges. Such heterometallic clusters are important cofactors in many metalloenzymes, where it is speculated that the redox-inactive constituent ion of the cluster serves to optimize its redox potential for electron transfer or catalysis. A principal example is the oxygen-evolving complex in photosystem II of natural photosynthesis, a Mn4CaO5 cofactor that oxidizes water into dioxygen, protons and electrons. Calcium is critical for catalytic function, but its precise role is not yet established. In analogy to synthetic complexes it has been suggested that Ca(2+) fine-tunes the redox potential of the manganese cluster. Here we evaluate this hypothesis by computing the relative redox potentials of substituted derivatives of the oxygen-evolving complex with the cations Sr(2+), Gd(3+), Cd(2+), Zn(2+), Mg(2+), Sc(3+), Na(+) and Y(3+) for two sequential transitions of its catalytic cycle. The theoretical approach is validated with a series of experimentally well-characterized Mn3AO4 cubane complexes that are structural mimics of the enzymatic cluster. Our results reproduce perfectly the experimentally observed correlation between the redox potential and the Lewis acidities of redox-inactive cations for the synthetic complexes. However, it is conclusively demonstrated that this correlation does not hold for the oxygen evolving complex. In the enzyme the redox potential of the cluster only responds to the charge of the redox-inactive cations and remains otherwise insensitive to their precise identity, precluding redox-tuning of the metal cluster as a primary role for Ca(2+) in biological water oxidation. PMID:26762578

  1. Inactive end cell assembly for fuel cells for improved electrolyte management and electrical contact

    DOEpatents

    Yuh, Chao-Yi; Farooque, Mohammad; Johnsen, Richard

    2007-04-10

    An assembly for storing electrolyte in a carbonate fuel cell is provided. The combination of a soft, compliant and resilient cathode current collector and an inactive anode part including a foam anode in each assembly mitigates electrical contact loss during operation of the fuel cell stack. In addition, an electrode reservoir in the positive end assembly and an electrode sink in the negative end assembly are provided, by which ribbed and flat cathode members inhibit electrolyte migration in the fuel cell stack.

  2. Food reward in active compared to inactive men: Roles for gastric emptying and body fat.

    PubMed

    Horner, Katy M; Finlayson, Graham; Byrne, Nuala M; King, Neil A

    2016-06-01

    Habitual exercise could contribute to weight management by altering processes of food reward via the gut-brain axis. We investigated hedonic processes of food reward in active and inactive men and characterised relationships with gastric emptying and body fat. Forty-four men (active: n=22; inactive: n=22, BMI range 21-36kg/m(2); percent fat mass range 9-42%) were studied. Participants were provided with a standardised fixed breakfast and an ad libitum lunch meal 5h later. Explicit liking, implicit wanting and preference among high-fat, low-fat, sweet and savoury food items were assessed immediately post-breakfast (fed state) and again pre-lunch (hungry state) using the Leeds Food Preference Questionnaire. Gastric emptying was assessed by (13)C-octanoic acid breath test. Active individuals exhibited a lower liking for foods overall and a greater implicit wanting for low-fat savoury foods in the fed state, compared to inactive men. Differences in the fed state remained significant after adjusting for percent fat mass. Active men also had a greater increase in liking for savoury foods in the interval between breakfast and lunch. Faster gastric emptying was associated with liking for savoury foods and with an increase in liking for savoury foods in the postprandial interval. In contrast, greater implicit wanting for high-fat foods was associated with slower gastric emptying. These associations were independent of each other, activity status and body fat. In conclusion, active and inactive men differ in processes of food reward. The rate of gastric emptying may play a role in the association between physical activity status and food reward, via the gut-brain axis. PMID:27072508

  3. Arctic Ground Squirrels Limit Bone Loss during the Prolonged Physical Inactivity Associated with Hibernation.

    PubMed

    Wojda, Samantha J; Gridley, Richard A; McGee-Lawrence, Meghan E; Drummer, Thomas D; Hess, Ann; Kohl, Franziska; Barnes, Brian M; Donahue, Seth W

    2016-01-01

    Prolonged disuse (e.g., physical inactivity) typically results in increased bone porosity, decreased mineral density, and decreased bone strength, leading to increased fracture risk in many mammals. However, bears, marmots, and two species of ground squirrels have been shown to preserve macrostructural bone properties and bone strength during long seasons of hibernation while they remain mostly inactive. Some small hibernators (e.g., 13-lined ground squirrels) show microstructural bone loss (i.e., osteocytic osteolysis) during hibernation, which is not seen in larger hibernators (e.g., bears and marmots). Arctic ground squirrels (Urocitellus parryii) are intermediate in size between 13-lined ground squirrels and marmots and are perhaps the most extreme rodent hibernator, hibernating for up to 8 mo annually with body temperatures below freezing. The goal of this study was to quantify the effects of hibernation and inactivity on cortical and trabecular bone properties in arctic ground squirrels. Cortical bone geometrical properties (i.e., thickness, cross-sectional area, and moment of inertia) at the midshaft of the femur were not different in animals sampled over the hibernation and active seasons. Femoral ultimate stress tended to be lower in hibernators than in summer animals, but toughness was not affected by hibernation. The area of osteocyte lacunae was not different between active and hibernating animals. There was an increase in osteocytic lacunar porosity in the hibernation group due to increased lacunar density. Trabecular bone volume fraction in the proximal tibia was unexpectedly greater in the hibernation group than in the active group. This study shows that, similar to other hibernators, arctic ground squirrels are able to preserve many bone properties during hibernation despite being physically inactive for up to 8 mo. PMID:27082526

  4. School Social Fragmentation, Economic Deprivation and Social Cohesion and Adolescent Physical Inactivity: A Longitudinal Study

    PubMed Central

    Pabayo, Roman; Janosz, Michel; Bisset, Sherri; Kawachi, Ichiro

    2014-01-01

    Objectives To examine the independent influence of school economic deprivation, social fragmentation, and social cohesion on the likelihood of participating in no physical activity among students. Methods Data are from a large-scale longitudinal study of schools based in disadvantaged communities in Quebec, Canada. Questionnaires were administered every year between 2002 and 2008 among n = 14,924 students aged 12 to 18 from a sample of 70 schools. Cross-sectional and longitudinal analyses were conducted. Multilevel modeling was utilized to account for the clustering of students within schools. Schools were categorized as being low, moderate or high economic deprivation, social fragmentation and social cohesion. Those who indicated that they do no participate in any physical activity during the week were identified as being physically inactive. Results In baseline multilevel cross-sectional analyses, adolescents attending schools in the highest (compared to the lowest) levels of socioeconomic deprivation and social fragmentation were more likely to be physically inactive (OR = 1.33, 95% CI = 1.03, 1.72; and OR = 1.24, 95% CI = 0.98, 1.56, respectively). Conversely, students attending schools with the highest cohesion were less likely to be physically inactive (OR = 0.78, 95% CI = 0.61, 0.99). In longitudinal analysis, physically active students who attended schools with the highest social fragmentation were more likely to become physically inactive over two years (OR = 1.65, 95% CI = 1.09, 2.51). Conclusion The school socioeconomic environment appears to be an important contextual influence on participation in no physical activity among adolescents. Following adolescents beyond two years is necessary to determine if these environments have a lasting effect on physical activity behavior. PMID:24932679

  5. Incomplete flagellar structures in Escherichia coli mutants.

    PubMed Central

    Suzuki, T; Komeda, Y

    1981-01-01

    Escherichia coli mutants with defects in 29 flagellar genes identified so far were examined by electron microscopy for possession of incomplete flagellar structures in membrane-associated fractions. The results are discussed in consideration of the known transcriptional interaction of flagellar genes. Hook-basal body structures were detected in flaD, flaS, flaT, flbC, and hag mutants. The flaE mutant had a polyhook-basal body structure. An intact basal body appeared in flaK mutants. Putative precursors of the basal body were detected in mutants with defects in flaM, flaU, flaV, and flaY. No structures homologous to the flagellar basal body or its parts were detected in mutants with defects in flaA, flaB, flaC, flaG, flaH, flaI, flaL, flaN, flaO, flaP, flaQ, flaR, flaW, flaX, flbA, flbB, and flbD. One flaZ mutant had an incomplete flagellar basal body structure and another formed no significant structure, suggesting that flaZ is responsible for both basal body assembly and the transcription of the hag gene. Images PMID:7007337

  6. Kasugamycin-dependent mutants of Escherichia coli.

    PubMed Central

    Dabbs, E R

    1978-01-01

    Kasugamycin-dependent mutants have been isolated from Escherichia coli B. They were obtained through mutagenesis with ethyl methane sulfonate or nitrosoguanidine in conjunction with an antibiotic underlay technique. In the case of nitrosoguanidine, dependent mutants were obtained at a frequency of about 3% of survivors growing up in the selection. In the case of ethyl methane sulfonate, the corresponding value was 1%. Nineteen mutants showing a kasugamycin-dependent phenotype were studied. In terms of response to various temperatures and antibiotic concentrations, they were very heterogeneous, although most fell into two general classes. Genetic analysis indicated that in at least some cases, the kasugamycin-dependent phenotype was the product of two mutations. Two-dimensional gel electropherograms revealed alterations in the ribosomal proteins of seven mutants. One mutant had an alteration in protein S13, and one had an alteration in protein L14. Three showed changes in protein S9. Each of two mutants had changes in two proteins, S18 and L11. Three of these mutants additionally had protein S18 occurring in a partly altered, partly unaltered form. Images PMID:363701

  7. Using gender-based analyses to understand physical inactivity among women in Yellowstone County, Montana.

    PubMed

    Duin, Diane K; Golbeck, Amanda L; Keippel, April Ennis; Ciemins, Elizabeth; Hanson, Hillary; Neary, Tracy; Fink, Heather

    2015-08-01

    Physical inactivity contributes to many health problems. Gender, the socially constructed roles and activities deemed appropriate for men and women, is an important factor in women's physical inactivity. To better understand how gender influences participation in leisure-time physical activity, a gender analysis was conducted using sex-disaggregated data from a county-wide health assessment phone survey and a qualitative analysis of focus group transcripts. From this gender analysis, several gender-based constraints emerged, including women's roles as caregivers, which left little time or energy for physical activity, women's leisure time activities and hobbies, which were less active than men's hobbies, and expectations for women's appearance that made them uncomfortable sweating in front of strangers. Gender-based opportunities included women's enjoyment of activity as a social connection, less rigid gender roles for younger women, and a sense of responsibility to set a good example for their families. The gender analysis was used to gain a deeper understanding of gender-based constraints and opportunities related to physical activity. This understanding is being used in the next step of our research to develop a gender-specific intervention to promote physical activity in women that addresses the underlying causes of physical inactivity through accommodation or transformation of those gender norms. PMID:25542368

  8. A Mononuclear Non-Heme Manganese(IV)-Oxo Complex Binding Redox-Inactive Metal Ions

    SciTech Connect

    Chen, Junying; Lee, Yong-Min; Davis, Katherine M.; Wu, Xiujuan; Seo, Mi Sook; Cho, Kyung-Bin; Yoon, Heejung; Park, Young Jun; Fukuzumi, Shunichi; Pushkar, Yulia N.; Nam, Wonwoo

    2013-05-29

    Redox-inactive metal ions play pivotal roles in regulating the reactivities of high-valent metal–oxo species in a variety of enzymatic and chemical reactions. A mononuclear non-heme Mn(IV)–oxo complex bearing a pentadentate N5 ligand has been synthesized and used in the synthesis of a Mn(IV)–oxo complex binding scandium ions. The Mn(IV)–oxo complexes were characterized with various spectroscopic methods. The reactivities of the Mn(IV)–oxo complex are markedly influenced by binding of Sc3+ ions in oxidation reactions, such as a ~2200-fold increase in the rate of oxidation of thioanisole (i.e., oxygen atom transfer) but a ~180-fold decrease in the rate of C–H bond activation of 1,4-cyclohexadiene (i.e., hydrogen atom transfer). The present results provide the first example of a non-heme Mn(IV)–oxo complex binding redox-inactive metal ions that shows a contrasting effect of the redox-inactive metal ions on the reactivities of metal–oxo species in the oxygen atom transfer and hydrogen atom transfer reactions.

  9. Using buriedness to improve discrimination between actives and inactives in docking.

    PubMed

    O'Boyle, Noel M; Brewerton, Suzanne C; Taylor, Robin

    2008-06-01

    A continuing problem in protein-ligand docking is the correct relative ranking of active molecules versus inactives. Using the ChemScore scoring function as implemented in the GOLD docking software, we have investigated the effect of scaling hydrogen bond, metal-ligand, and lipophilic interactions based on the buriedness of the interaction. Buriedness was measured using the receptor density, the number of protein heavy atoms within 8.0 A. Terms in the scaling functions were optimized using negative data, represented by docked poses of inactive molecules. The objective function was the mean rank of the scores of the active poses in the Astex Diverse Set (Hartshorn et al. J. Med. Chem., 2007, 50, 726) with respect to the docked poses of 99 inactives. The final four-parameter model gave a substantial improvement in the average rank from 18.6 to 12.5. Similar results were obtained for an independent test set. Receptor density scaling is available as an option in the recent GOLD release. PMID:18533645

  10. Swimming activity in dystonia musculorum mutant mice.

    PubMed

    Lalonde, R; Joyal, C C; Cote, C

    1993-07-01

    Dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar fibers, were evaluated in a visible platform swim test. It was found that dt mutants were slower to reach the platform than normal mice. However, the number of quadrants traversed was not higher in dt mutants. It is concluded that spinocerebellar fibers to the vermis are important in limb control during swimming but not in visuo-motor guidance (navigational skills) of the animal towards a visible goal, at least in regard to the quadrant measure. It is not excluded that a measure tracing their path may find a mild deviation from the goal. PMID:8327590

  11. Preferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors

    PubMed Central

    Yanamala, Naveena; Tirupula, Kalyan C; Klein-Seetharaman, Judith

    2008-01-01

    Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiological and pathological processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, we propose the hypothesis that positive and negative modulators will differentially stabilize the active and inactive conformations of the receptors, respectively. To test this hypothesis, we have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is experimentally known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. We find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%), the negative modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%), the positive modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86%) and 8/9 (89%) for ArgusLab and 10/14 (71%) and 7/9 (78%) for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by photochemical isomerization

  12. Is Moderate Red Wine Consumption Safe in Inactive Inflammatory Bowel Disease?

    PubMed Central

    Swanson, Garth R.; Tieu, Vanessa; Shaikh, Maliha; Forsyth, Chris; Keshavarzian, Ali

    2011-01-01

    Background Alcohol consumption is a potential trigger for inflammatory bowel disease (IBD) flare because of alcohol-induced oxidative stress and its deleterious effects on gut barrier function. Additionally, we have recently shown that alcohol consumption is associated with more symptoms in IBD. However, it is not known whether moderate daily alcohol consumption can modify IBD disease activity. To test what effects alcohol may have on patients with IBD, we evaluated the effect of moderate daily red wine for 1 week on two factors associated with recurrent IBD disease activity: intestinal permeability and stool calprotectin. Methods To assess the effects of moderate daily alcohol consumption on intestinal permeability and inflammation, we recruited 21 patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's disease (CD), and 7 healthy controls. All participants with IBD completed a validated questionnaire on disease activity (Crohn's disease activity index or ulcerative colitis clinical activity index), to confirm they had inactive disease. All subjects then underwent a baseline assessment that included a blood draw, urine collection after sugar challenge, and stool collection. Subjects then consumed 1–3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and repeated the three measures. Results No subjects flared during the study. Moderate alcohol consumption did not significantly change either clinical disease activity scores or C-reactive protein. In contrast to healthy subjects, daily consumption of red wine significantly (1) decreased stool calprotectin in IBD subjects from baseline (p = 0.001) and (2) increased intestinal permeability as measured by urinary lactulose/mannitol excretion (marker of small bowel permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large bowel permeability) in UC (p = 0.012). Conclusions One week of moderate consumption of red wine in inactive IBD was associated with a significant

  13. Effects of optical and geometrical properties on YORP effect for inactive satellites

    NASA Astrophysics Data System (ADS)

    Albuja, A.; Scheeres, D.

    2014-09-01

    With the increasing number of space debris in Earth orbit, it is important to understand the dynamics of these objects. Initial studies have demonstrated that the Yarkovsky, O'Keefe, Radzievskii, Paddack (YORP) effect on inactive satellite needs to be further explored as it could be noticeably affecting the rotational dynamics of these Earth orbiting objects. The YORP effect is created by torques resulting from light and thermal energy being re-emitted from the surface of a body. This effect has been well studied and observed to affect the spin states of asteroids. The purpose of this paper is to further investigate YORP in the realm of large inactive Geosynchronous Earth Orbit (GEO) satellites. The forces that cause the YORP effect are highly dependent on the optical, thermal and geometrical properties of the facets making up the surface of the body being analyzed. This paper focuses on exploring the effect of these properties on the YORP effect for inactive satellite. Two different satellite models that represent bus types of inactive satellites in GEO are used for this study. By varying the optical, thermal and geometrical properties of these models, in a manner that remains consistent with realistic satellite parameters, we can understand the relationship between these properties and the torques created by YORP. Having this knowledge allows for better understanding of the possible attitude states (spin rate and obliquity) for uncontrolled satellites in GEO. This information can then be used to make predictions of the long-term behavior of the rotation rate and obliquity of these objects. Categories of potential final states for defunct GEO satellites can then be created based on geometrical and optical properties (e.g. spin up continuously, spin down continuously, etc.). This allows the population of inactive GEO satellites to be studied in a more general sense and final attitude states for these objects can be quickly identified. Furthermore, an understanding

  14. Distribution and abundance of nontoxic mutants of cyanobacteria in lakes of the Alps.

    PubMed

    Ostermaier, Veronika; Kurmayer, Rainer

    2009-08-01

    The filamentous cyanobacterium Planktothrix rubescens frequently occurs in deep and stratified lakes in the temperate region of the northern hemisphere and is a known producer of the hepatotoxic secondary metabolite microcystin. These cyclic heptapeptides are synthesized nonribosomally via large enzyme complexes encoded by the microcystin (mcy) synthetase gene cluster. The occurrence of cyanobacterial strains lacking microcystin, but containing the mcy gene cluster has been reported repeatedly; it was shown that this inactivation is due to mutations such as gene deletion events and the insertion of transposable elements. In the present study, 12 lakes in Austria, Germany, and Switzerland were sampled from July 2005 to October 2007, and the proportion of inactive mcy genotypes was quantified in relation to the total population of the red-pigmented filamentous cyanobacterium Planktothrix by means of quantitative polymerase chain reaction. In total, four different mutations were quantified, namely two insertions affecting mcyD, one insertion affecting mcyA, and a deletion within mcyH and mcyA. The mutations occurred over a wide range of population densities (40-570,000 filaments L(-1)), and their abundance was found to be positively correlated with population density. However, on average, all nontoxic mutants were found in a low proportion only (min 0%, mean 6.5% +/- 1.1 (SE), max 52% of the total population). The genotype containing the mcyHA deletion had a significantly higher proportion (min 0%, mean 3.7% +/- 1, max 52%) when compared with all the genotypes containing insertions within the mcy gene cluster (min 0%, mean 2.8% +/- 0.7, max 24%). The results demonstrate that the occurrence of inactive mcy genotypes is linearly related to the population density, and selective sweeps of nontoxic mutants did not occur during the transition from prebloom to bloom conditions. PMID:19214623

  15. Macrobenthos community structure and trophic relationships within active and inactive Pacific hydrothermal sediments

    NASA Astrophysics Data System (ADS)

    Levin, Lisa A.; Mendoza, Guillermo F.; Konotchick, Talina; Lee, Raymond

    2009-09-01

    Hydrothermal fluids passing through sediments create a habitat hypothesized to influence the community structure of infaunal macrobenthos. Here we characterize the density, biomass, species composition, diversity, distributions, lifestyle, and nutritional sources of macroinfauna in hydrothermal sediments in NE and SW Pacific settings, and draw comparisons in search of faunal attributes characteristic of this habitat. There is increasing likelihood that seafloor massive sulfide deposits, associated with active and inactive hydrothermal venting, will be mined commercially. This creates a growing imperative for a more thorough understanding of the structure, dynamics, and resilience of the associated sediment faunas, and has stimulated the research presented here. Macrobenthic assemblages were studied at Manus Basin (1430-1634 m, Papua New Guinea [PNG]) as a function of location (South Su vs. Solwara 1), and hydrothermal activity (active vs. inactive), and at Middle Valley (2406-2411 m, near Juan de Fuca Ridge) as a function of habitat (active clam bed, microbial mat, hot mud, inactive background sediment). The studies conducted in PNG formed part of the environmental impact assessment work for the Solwara 1 Project of Nautilus Minerals Niugini Limited. We hypothesized that hydrothermally active sites should support (a) higher densities and biomass, (b) greater dominance and lower diversity, (c) a higher fraction of deposit feeders, and (d) greater isotopic evidence for chemosynthetic food sources than inactive sites. Manus Basin macrofauna generally had low density (<1000 ind. m -2) and low biomass (0.1-1.07 g m -2), except for the South Su active site, which had higher density (3494 ind. m -2) and biomass (11.94 g m -2), greater dominance (R1D=76%), lower diversity and more spatial (between-core) homogeneity than the Solwara 1 and South Su inactive sites. Dominant taxa at Manus Basin were Spionidae ( Prionospio sp.) in active sediments, and tanaids and deposit

  16. Novel Class of Mutations of pilS Mutants, Encoding Plasmid R64 Type IV Prepilin: Interface of PilS-PilV Interactions▿

    PubMed Central

    Shimoda, Eriko; Muto, Tatsuya; Horiuchi, Takayuki; Furuya, Nobuhisa; Komano, Teruya

    2008-01-01

    The type IV pili of plasmid R64 belonging to the type IVB group are required only for liquid mating. They consist of the major and minor components PilS pilin and PilV adhesin, respectively. PilS pilin is first synthesized as a 22-kDa prepilin from the pilS gene and is then processed to a 19-kDa mature pilin by PilU prepilin peptidase. In a previous genetic analysis, we identified four classes of the pilS mutants (T. Horiuchi and T. Komano, J. Bacteriol. 180:4613-4620, 1998). The products of the class I pilS mutants were not processed by prepilin peptidase; the products of the class II mutants were not secreted; in the class III mutants type IV pili with reduced activities in liquid mating were produced; and in the class IV mutants type IV pili with normal activities were produced. Here, we describe a novel class, class V, of pilS mutants. Mutations in the pilS gene at Gly-56 or Tyr-57 produced type IV pili lacking PilV adhesin, which were inactive in liquid mating. Residues 56 and 57 of PilS pilin are suggested to function as an interface of PilS-PilV interactions. PMID:18065540

  17. Altered calmodulin activity in fluphenazine-resistant mutant strains. Pleiotropic effect on development and cellular organization in Volvox carteri.

    PubMed

    Kurn, N; Sela, B A

    1981-12-01

    Genetically altered calmodulin activity in spontaneously derived mutant strains, which were selected for resistance to the toxic effect of a specific inhibitor, the phenothiazine drug fluphenazine, is demonstrated. Partially purified calmodulin preparations from wild-type and fluphenazine-resistant strains of the multicellular alga Volvox carteri, were tested for the ability to activate Ca2+-ATPase of the erythrocyte membranes, and the inhibition of this stimulatory activity by fluphenazine. Unlike the preparation obtained from wild-type cells, mutant calmodulin is shown to be insensitive to fluphenazine inhibition, in one case, and calmodulin from another strain was found to be inactive in vitro, i.e. it did not activate Ca2+-ATPase. The pleiotropic phenotype of the spontaneously derived mutant strains involved aberrant multicellular organization and hormone-independent commitment of the multipotent asexual reproductive cells, gonodia, to sexual development. These results clearly implicate calmodulin in the control of development and morphogenesis in this simple multicellular eukaryote. In addition, intracellular inhibition of calmodulin in wild-type cells is shown to block the morphogenic process of embryo inversion and to arrest motility. The availability of mutant calmodulin will facilitate further investigation of the role of this ubiquitous regulatory protein in the control of development and differentiation in multicellular eukarytes, as well as the fine structure/function relationship with regard to calmodulin modulation of a wide variety of cellular processes. PMID:6459931

  18. Phosphoglucomutase Mutants of Escherichia coli K-12

    PubMed Central

    Adhya, Sankar; Schwartz, Maxime

    1971-01-01

    Bacteria with strongly depressed phosphoglucomutase (EC 2.7.5.1) activity are found among the mutants of Escherichia coli which, when grown on maltose, accumulate sufficient amylose to be detectable by iodine staining. These pgm mutants grow poorly on galactose but also accumulate amylose on this carbon source. Growth on lactose does not produce high amylose but, instead, results in the induction of the enzymes of maltose metabolism, presumably by accumulation of maltose. These facts suggest that the catabolism of glucose-1-phosphate is strongly depressed in pgm mutants, although not completely abolished. Anabolism of glucose-1-phosphate is also strongly depressed, since amino acid- or glucose-grown pgm mutants are sensitive to phage C21, indicating a deficiency in the biosynthesis of uridine diphosphoglucose or uridine diphosphogalactose, or both. All pgm mutations isolated map at about 16 min on the genetic map, between purE and the gal operon. PMID:4942754

  19. Cooperative Interaction Within RNA Virus Mutant Spectra.

    PubMed

    Shirogane, Yuta; Watanabe, Shumpei; Yanagi, Yusuke

    2016-01-01

    RNA viruses usually consist of mutant spectra because of high error rates of viral RNA polymerases. Growth competition occurs among different viral variants, and the fittest clones predominate under given conditions. Individual variants, however, may not be entirely independent of each other, and internal interactions within mutant spectra can occur. Examples of cooperative and interfering interactions that exert enhancing and suppressing effects on replication of the wild-type virus, respectively, have been described, but their underlying mechanisms have not been well defined. It was recently found that the cooperation between wild-type and variant measles virus genomes produces a new phenotype through the heterooligomer formation of a viral protein. This observation provides a molecular mechanism underlying cooperative interactions within mutant spectra. Careful attention to individual sequences, in addition to consensus sequences, may disclose further examples of internal interactions within mutant spectra. PMID:26162566

  20. Mutant p53: one name, many proteins

    PubMed Central

    Freed-Pastor, William A.; Prives, Carol

    2012-01-01

    There is now strong evidence that mutation not only abrogates p53 tumor-suppressive functions, but in some instances can also endow mutant proteins with novel activities. Such neomorphic p53 proteins are capable of dramatically altering tumor cell behavior, primarily through their interactions with other cellular proteins and regulation of cancer cell transcriptional programs. Different missense mutations in p53 may confer unique activities and thereby offer insight into the mutagenic events that drive tumor progression. Here we review mechanisms by which mutant p53 exerts its cellular effects, with a particular focus on the burgeoning mutant p53 transcriptome, and discuss the biological and clinical consequences of mutant p53 gain of function. PMID:22713868

  1. Arabidopsis mutants with a reduced seed dormancy.

    PubMed Central

    Léon-Kloosterziel, K M; van de Bunt, G A; Zeevaart, J A; Koornneef, M

    1996-01-01

    The development of seed dormancy is an aspect of seed maturation, the last stage of seed development. To isolate mutants of Arabidopsis thaliana that are affected in this process, we selected directly for the absence of dormancy among freshly harvested M2 seeds. The screen yielded two mutants exhibiting a reduced dormancy, rdo1 and rdo2, that are specifically affected in dormancy determined by the embryo. The rdo1 and rdo2 mutants show normal levels of abscisic acid and the same sensitivity to abscisic acid, ethylene, auxin, and cytokinin as the wild type. The rdo2 mutant but not the rdo1 mutant has a reduced sensitivity to the gibberellin biosynthesis inhibitor tetcyclacis. Double-mutant analysis suggested that the RDO1 and RDO2 genes are involved in separate pathways leading to the development of dormancy. We assume that the RDO2 gene controls a step in the induction of dormancy that is most likely induced by abscisic acid and is expressed as an increase of the gibberellin requirement for germination. PMID:8587986

  2. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors.

    PubMed

    Jia, Yong; Yun, Cai-Hong; Park, Eunyoung; Ercan, Dalia; Manuia, Mari; Juarez, Jose; Xu, Chunxiao; Rhee, Kevin; Chen, Ting; Zhang, Haikuo; Palakurthi, Sangeetha; Jang, Jaebong; Lelais, Gerald; DiDonato, Michael; Bursulaya, Badry; Michellys, Pierre-Yves; Epple, Robert; Marsilje, Thomas H; McNeill, Matthew; Lu, Wenshuo; Harris, Jennifer; Bender, Steven; Wong, Kwok-Kin; Jänne, Pasi A; Eck, Michael J

    2016-06-01

    The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase, but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor. Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant, but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond. All current EGFR TKIs target the ATP-site of the kinase, highlighting the need for therapeutic agents with alternative mechanisms of action. Here we describe the rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. The crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. However, as a single agent it is not effective in blocking EGFR-driven proliferation in cells owing to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state. We observe marked synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization, rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR(L858R/T790M) and by EGFR(L858R/T790M/C797S), a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors. PMID:27251290

  3. 38 CFR 4.88c - Ratings for inactive nonpulmonary tuberculosis initially entitled after August 19, 1968.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88c Ratings for inactive nonpulmonary... active tuberculosis 100 Thereafter: Rate residuals under the specific body system or systems...

  4. 38 CFR 4.88c - Ratings for inactive nonpulmonary tuberculosis initially entitled after August 19, 1968.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88c Ratings for inactive nonpulmonary... active tuberculosis 100 Thereafter: Rate residuals under the specific body system or systems...

  5. 38 CFR 4.88c - Ratings for inactive nonpulmonary tuberculosis initially entitled after August 19, 1968.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88c Ratings for inactive nonpulmonary... active tuberculosis 100 Thereafter: Rate residuals under the specific body system or systems...

  6. 38 CFR 4.88c - Ratings for inactive nonpulmonary tuberculosis initially entitled after August 19, 1968.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Infectious Diseases, Immune Disorders and Nutritional Deficiencies § 4.88c Ratings for inactive nonpulmonary... active tuberculosis 100 Thereafter: Rate residuals under the specific body system or systems...

  7. Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity.

    PubMed

    Zderic, Theodore W; Hamilton, Marc T

    2006-01-01

    Physical inactivity is a risk factor for lipoprotein disorders and the metabolic syndrome. Physical inactivity has a powerful effect on suppressing lipoprotein lipase (LPL) activity in skeletal muscle, the rate-limiting enzyme for hydrolysis of triglyceride (TG)-rich lipoproteins. We tested the ability of several compounds to prevent the decrease in LPL. The present study minimized standing and ordinary light nonexercise movements in rats to compare the effects of inactivity and nonexercise activity thermogenesis (NEAT) on LPL activity. The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA), whereas inhibitors of TNF-alpha, inducible nitric oxide synthase, and NF-kappaB had no such effect. NA was administered at a dose known to acutely impede the appearance of plasma TG from the liver and free fatty acids from adipose tissue, and it was effective at intentionally lowering plasma lipid concentrations to the same level in active and inactive groups. As measured from heparin-releasable LPL activity, LPL in the microvasculature of the most oxidative muscles was approximately 90% lower in the inactive group compared with controls, and this suppression was completely blocked by NA. In contrast to inactivity, NA did not raise muscle LPL in ambulatory controls, whereas a large exogenous fat delivery did decrease LPL activity. In vitro control studies revealed that NA did not have a direct effect on skeletal muscle LPL activity. In conclusion, physical inactivity amplifies the ability of plasma lipids to suppress muscle LPL activity. The light ambulatory contractions responsible for NEAT are sufficient for mitigating these deleterious effects. PMID:16195388

  8. Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

    PubMed Central

    Kennedy, K. David; AnithaChristy, S. A.; Buie, LaKisha K.; Borrás, Teresa

    2012-01-01

    Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma. PMID:22615763

  9. Predictors of hazardous drinking, tobacco smoking and physical inactivity in vocational school students

    PubMed Central

    2013-01-01

    Background Tobacco smoking, hazardous drinking and physical inactivity during adolescence are risk factors that are associated with poorer health in adulthood. The identification of subgroups of young people with a high prevalence of one or more of these risk factors allows an optimised allocation of preventive measures. This study aimed at investigating hazardous drinking, tobacco smoking and physical inactivity as well as their associations and demographic predictors in vocational school students. Methods Out of 57 contacted vocational schools in Switzerland, a total of 24 schools participated in a survey assessing gender, age, immigrant background, educational attainment and vocational field as well as the above mentioned health risk factors. Out of the 2659 students present in 177 included vocational school classes, 2647 (99.5%) completed the survey. Binary logistic regression analyses were conducted to investigate the demographic predictors of each health risk factor and a multinomial logistic regression analysis was conducted to investigate predictors of different risk factor combinations. Results Of the surveyed students, 79.4% showed at least one risk factor, 43.6% showed two or more and 9.6% showed all three health risk factors. Hazardous drinking was more prevalent in male, physical inactivity was more prevalent in female vocational school students. The proportion of students with low physical activity and tobacco smoking increased with increasing age. While the combination of hazardous drinking and tobacco smoking was higher in males, the other risk factor combinations were observed particularly among females. Conclusions Multiple risk factors were ascertained in a significant proportion of vocational school students. Specifically, tobacco smoking and hazardous drinking were coexistent. The study underlines the need for preventive measures in specific subpopulations of adolescents and young adults with lower educational level. PMID:23672294

  10. Previously unrecognized now-inactive strand of the North Anatolian fault in the Thrace basin

    SciTech Connect

    Perincek, D. )

    1988-08-01

    The North Anatolian fault is a major 1,200 km-long transform fault bounding the Anatolian plate to the north. It formed in late middle Miocene time as a broad shear zone with a number of strands splaying westward in a horsetail fashion. Later, movement became localized along the stem, and the southerly and northerly splays became inactive. One such right-lateral, now-inactive splay is the west-northwest-striking Thrace strike-slip fault system, consisting of three subparallel strike-slip faults. From north to south these are the Kirklareli, Lueleburgaz, and Babaeski fault zones, extending {plus minus} 130 km along the strike. The Thrace fault zone probably connected with the presently active northern strand of the North Anatolian fault in the Sea of Marmara in the southeast and may have joined the Plovdiv graben zone in Bulgaria in the northwest. The Thrace basin in which the Thrace fault system is located, is Cenozoic with a sedimentary basin fill from middle Eocene to Pliocene. The Thrace fault system formed in pre-Pliocene time and had become inactive by the Pliocene. Strike-slip fault zones with normal and reverse separation are detected by seismic reflection profiles and subsurface data. Releasing bend extensional structures (e.g., near the town of Lueleburgaz) and restraining bend compressional structures (near Vakiflar-1 well) are abundant on the fault zones. Umurca and Hamitabad fields are en echelon structures on the Lueleburgaz fault zone. The Thrace strike-slip fault system has itself a horsetail shape, the various strands of which become younger southward. The entire system died before the Pliocene, and motion on the North Anatolian fault zone began to be accommodated in the Sea of Marmara region. Thus the Thrace fault system represents the oldest strand of the North Anatolian fault in the west.

  11. Spinal atypical protein kinase C activity is necessary to stabilize inactivity-induced phrenic motor facilitation

    PubMed Central

    Strey, K.A.; Nichols, N.L.; Baertsch, N.A.; Broytman, O.; Baker-Herman, T.L.

    2012-01-01

    The neural network controlling breathing must establish rhythmic motor output at a level adequate to sustain life. Reduced respiratory neural activity elicits a novel form of plasticity in circuits driving the diaphragm known as inactivity-induced phrenic motor facilitation (iPMF), a rebound increase in phrenic inspiratory output observed once respiratory neural drive is restored. The mechanisms underlying iPMF are unknown. Here, we demonstrate in anesthetized rats that spinal mechanisms give rise to iPMF, and that iPMF consists of at least two mechanistically distinct phases: 1) an early, labile phase that requires atypical PKC (PKCζ and/or PKCΙ/λ) activity to transition to a 2) late, stable phase. Early (but not late) iPMF is associated with increased interactions between PKCζ/Ι and the scaffolding protein ZIP/p62 in spinal regions associated with the phrenic motor pool. Although PKCζ/Ι activity is necessary for iPMF, spinal aPKC activity is not necessary for phrenic long-term facilitation (pLTF) following acute intermittent hypoxia, an activity-independent form of spinal respiratory plasticity. Thus, while iPMF and pLTF both manifest as prolonged increases in phrenic burst amplitude, they arise from distinct spinal cellular pathways. Our data are consistent with the hypotheses that: 1) local mechanisms sense and respond to reduced respiratory-related activity in the phrenic motor pool, and 2) inactivity-induced increases in phrenic inspiratory output require local PKCζ/Ι activity to stabilize into a long-lasting iPMF. Although the physiological role of iPMF is unknown, we suspect that iPMF represents a compensatory mechanism, assuring adequate motor output in a physiological system where prolonged inactivity ends life. PMID:23152633

  12. Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity.

    PubMed

    Roberts, Michael D; Company, Joseph M; Brown, Jacob D; Toedebusch, Ryan G; Padilla, Jaume; Jenkins, Nathan T; Laughlin, M Harold; Booth, Frank W

    2012-08-01

    According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2-19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6-11 yr old fail to obtain the recommended 60 min/day of physical activity and 92% of adolescents fail to achieve this goal [Troiano et al. Med Sci Sports Exerc. 40, 2008]. Nonetheless, invasive mechanistic studies in children linking diminished physical activity with metabolic maladies are lacking for obvious ethical reasons. The rodent wheel lock (WL) model was adopted by our laboratory and others to study how different organ systems of juvenile rats respond to a cessation of daily physical activity. Our WL model houses rats in cages equipped with voluntary running wheels starting at 28 days of age. After a certain period of voluntary running (3 to 6 wk), the wheels are locked, thus preventing the rats' primary source of physical activity. The studies discussed herein suggest that obesity-associated maladies including skeletal muscle insulin resistance, hypothalamic leptin resistance, fatty acid oxidation impairments in skeletal muscle and adipose tissue, nonalcoholic fatty liver disease, and endothelial dysfunction are initiated in juvenile animals that are restrained from voluntary exercise via WL. The use of the juvenile rodent WL or other inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity. PMID:22696577

  13. Spinal atypical protein kinase C activity is necessary to stabilize inactivity-induced phrenic motor facilitation.

    PubMed

    Strey, Kristi A; Nichols, Nicole L; Baertsch, Nathan A; Broytman, Oleg; Baker-Herman, Tracy L

    2012-11-14

    The neural network controlling breathing must establish rhythmic motor output at a level adequate to sustain life. Reduced respiratory neural activity elicits a novel form of plasticity in circuits driving the diaphragm known as inactivity-induced phrenic motor facilitation (iPMF), a rebound increase in phrenic inspiratory output observed once respiratory neural drive is restored. The mechanisms underlying iPMF are unknown. Here, we demonstrate in anesthetized rats that spinal mechanisms give rise to iPMF and that iPMF consists of at least two mechanistically distinct phases: (1) an early, labile phase that requires atypical PKC (PKCζ and/or PKCι/λ) activity to transition to a (2) late, stable phase. Early (but not late) iPMF is associated with increased interactions between PKCζ/ι and the scaffolding protein ZIP (PKCζ-interacting protein)/p62 in spinal regions associated with the phrenic motor pool. Although PKCζ/ι activity is necessary for iPMF, spinal atypical PKC activity is not necessary for phrenic long-term facilitation (pLTF) following acute intermittent hypoxia, an activity-independent form of spinal respiratory plasticity. Thus, while iPMF and pLTF both manifest as prolonged increases in phrenic burst amplitude, they arise from distinct spinal cellular pathways. Our data are consistent with the hypotheses that (1) local mechanisms sense and respond to reduced respiratory-related activity in the phrenic motor pool and (2) inactivity-induced increases in phrenic inspiratory output require local PKCζ/ι activity to stabilize into a long-lasting iPMF. Although the physiological role of iPMF is unknown, we suspect that iPMF represents a compensatory mechanism, assuring adequate motor output in a physiological system in which prolonged inactivity ends life. PMID:23152633

  14. Enzymatically Inactive Procaspase 1 stabilizes the ASC Pyroptosome and Supports Pyroptosome Spreading during Cell Division.

    PubMed

    Stein, Robert; Kapplusch, Franz; Heymann, Michael Christian; Russ, Susanne; Staroske, Wolfgang; Hedrich, Christian Michael; Rösen-Wolff, Angela; Hofmann, Sigrun Ruth

    2016-08-26

    Caspase-1 is a key player during the initiation of pro-inflammatory innate immune responses, activating pro-IL-1β in so-called inflammasomes. A subset of patients with recurrent febrile episodes and systemic inflammation of unknown origin harbor mutations in CASP1 encoding caspase-1. CASP1 variants result in reduced enzymatic activity of caspase-1 and impaired IL-1β secretion. The apparent paradox of reduced IL-1β secretion but systemic inflammation led to the hypothesis that CASP1 mutations may result in variable protein interaction clusters, thus activating alternative signaling pathways. To test this hypothesis, we established and characterized an in vitro system of transduced immortalized murine macrophages expressing either WT or enzymatically inactive (p.C284A) procaspase-1 fusion reporter proteins. Macrophages with variant p.C284A caspase-1 did not secrete IL-1β and exhibited reduced inflammatory cell death, referred to as pyroptosis. Caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) formed cytosolic macromolecular complexes (so-called pyroptosomes) that were significantly increased in number and size in cells carrying the p.C284A caspase-1 variant compared with WT caspase-1. Furthermore, enzymatically inactive caspase-1 interacted with ASC longer and with increased intensity compared with WT caspase-1. Applying live cell imaging, we documented for the first time that pyroptosomes containing enzymatically inactive variant p.C284A caspase-1 spread during cell division. In conclusion, variant p.C284A caspase-1 stabilizes pyroptosome formation, potentially enhancing inflammation by two IL-1β-independent mechanisms: pyroptosomes convey an enhanced inflammatory stimulus through the recruitment of additional proteins (such as RIP2, receptor interacting protein kinase 2), which is further amplified through pyroptosome and cell division. PMID:27402835

  15. Remedial action plan for stabilization of the inactive uranium mill tailings site at Monument Valley, Arizona

    SciTech Connect

    1986-02-01

    This Remedial Action Plan (RAP) has been developed to serve a two-fold purpose. It presents the series of activities which are proposed by the U.S. Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uranium processing site located near Monument Valley, Arizona It also serves to document the concurrence of both the Navajo Nation and the U.S. Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by NRC, becomes Appendix B of the Cooperative Agreement.

  16. Living in a Box or Call of the Wild? Revisiting Lifetime Inactivity and Sarcopenia

    PubMed Central

    Hindle, Allyson

    2011-01-01

    Abstract Significance The accepted effects of aging in mammalian skeletal muscle are progressive atrophy and weakening, or sarcopenia. Canonical hallmarks of aging in skeletal muscle include a reduction in muscle fiber cross-sectional area, a loss in muscle fibers through apoptosis and denervation, and infiltration of connective tissue or fibrosis. Emerging thought suggests that pro-inflammatory signaling and oxidative stress may contribute to sarcopenia. Critical Issues Unfortunately, most of the mammalian models used to examine and understand sarcopenia are confounded by the pervasive influence of prolonged physical inactivity. Further, the potential for underlying metabolic disorder and chronic disease (e.g., type II diabetes and cardiovascular disease) may accelerate skeletal muscle wasting. Because physical inactivity may share elevated pro-inflammatory (tumor necrosis factor-alpha and inducible nitric oxide synthase) and insufficient stress response (insulin-like growth factor-1 [IGF-1], heat-shock protein 25 [HSP25], NAD-dependent deacetylase sirtuin-3 [SIRT-3], and peroxisome proliferator-activated receptor-gamma coactivator 1[PGC-1α]) signaling with aging and chronic disease, it is critical to distinguish true aging from chronic inactivity or underlying disease. Conversely, the efficacy of exercise and caloric restrictive interventions against sarcopenia in aging populations appears highly effective when (a) conducted across the lifespan, or (b) at higher intensities when commenced in middle age or later. Recent Advances While the prospective mechanisms by which exercise or daily activity provide have not been elucidated, upregulation of HSPs, PGC-1α, and IGF-1 may ameliorate inflammatory signaling, apoptosis, and sarcopenia. Limited data indicate that the aging phenotype exhibited by mammals living in their natural habitat (Weddell seal and shrews) express limited apoptosis and fiber atrophy, whereas significant collagen accumulation remains. In

  17. Methylation of the mouse hprt gene differs on the active and inactive X chromosomes.

    PubMed Central

    Lock, L F; Melton, D W; Caskey, C T; Martin, G R

    1986-01-01

    It has been proposed that DNA methylation is involved in the mechanism of X inactivation, the process by which equivalence of levels of X-linked gene products is achieved in female (XX) and male (XY) mammals. In this study, Southern blots of female and male DNA digested with methylation-sensitive restriction endonucleases and hybridized to various portions of the cloned mouse hprt gene were compared, and sites within the mouse hprt gene were identified that are differentially methylated in female and male cells. The extent to which these sites are methylated when carried on the active and inactive X chromosomes was directly determined in a similar analysis of DNA from clonal cell lines established from a female embryo derived from a mating of two species of mouse, Mus musculus and Mus caroli. The results revealed two regions of differential methylation in the mouse hprt gene. One region, in the first intron of the gene, includes four sites that are completely unmethylated when carried on the active X and extensively methylated when carried on the inactive X. These same sites are extensively demethylated in hprt genes reactivated either spontaneously or after 5-azacytidine treatment. The second region includes several sites in the 3' 20kilobases of the gene extending from exon 3 to exon 9 that show the converse pattern; i.e., they are completely methylated when carried on the active X and completely unmethylated when carried on the inactive X. At least one of these sites does not become methylated after reactivation of the gene. The results of this study, together with the results of previous studies by others of the human hprt gene, indicate that these regions of differential methylation on the active and inactive X are conserved between mammalian species. Furthermore, the data described here are consistent with the idea that at least the sites in the 5' region of the gene play a role in the X inactivation phenomenon and regulation of expression of the mouse hprt

  18. Arabian Oryx (Oryx leucoryx) Respond to Increased Ambient Temperatures with a Seasonal Shift in the Timing of Their Daily Inactivity Patterns.

    PubMed

    Davimes, Joshua G; Alagaili, Abdulaziz N; Gravett, Nadine; Bertelsen, Mads F; Mohammed, Osama B; Ismail, Khairy; Bennett, Nigel C; Manger, Paul R

    2016-08-01

    The Arabian oryx inhabits an environment where summer ambient temperatures can exceed 40 °C for extended periods of time. While the oryx uses a suite of adaptations that aid survival, the effects of this extreme environment on inactivity are unknown. To determine how the oryx manages inactivity seasonally, we measured the daily rhythm of body temperature and used fine-grain actigraphy, in 10 animals, to reveal when the animals were inactive in relation to ambient temperature and photoperiod. We demonstrate that during the cooler winter months, the oryx was inactive during the cooler parts of the 24-h day (predawn hours), showing a nighttime (nocturnal) inactivity pattern. In contrast, in the warmer summer months, the oryx displayed a bimodal inactivity pattern, with major inactivity bouts (those greater than 1 h) occurring equally during both the coolest part of the night (predawn hours) and the warmest part of the day (afternoon hours). Of note, the timing of the daily rhythm of body temperature did not vary seasonally, although the amplitude did change, leading to a seasonal alteration in the phase relationship between inactivity and the body temperature rhythm. Because during periods of inactivity the oryx were presumably asleep for much of the time, we speculate that the daytime shift in inactivity may allow the oryx to take advantage of the thermoregulatory physiology of sleep, which likely occurs when the animal is inactive for more than 1 h, to mitigate environmentally induced increases in body temperature. PMID:27154303

  19. Identification of novel attenuated Salmonella Enteritidis mutants.

    PubMed

    Chang, Jason; Pang, Ervinna; He, Haiqi; Kwang, Jimmy

    2008-06-01

    Salmonella Enteritidis is a major food-borne pathogen that causes nontyphoidal diarrhoea in humans. Infection of adult egg-laying hens usually results in symptomless carriage but in young chicks it may cause paratyphoid disease. It is not known whether S. Enteritidis requires genes additional to known virulence genes for systemic infection of young chickens. A transposon insertion library was created using S. Enteritidis 10/02, which yielded 1246 mutants. Of 384 mutants screened in chickens for attenuation (30.8% of insertion library), 12 (3.1%) had a 50% lethal dose at least 100 times that of the parental strain. Sequencing revealed insertions in genes involved in the biosynthesis of lipopolysaccharide, cell membrane, ATP biosynthesis, transcriptional regulation of virulence and the yhbC gene, which has an unknown function. Evaluation of in vitro virulence characteristics of a Delta yhbC mutant revealed that its ability to invade HeLa cells and survive within a chicken macrophage cell line (HD11) was significantly reduced. It was also less resistant to reactive oxygen and nitrogen intermediates and had a retarded growth rate. Chickens challenged with the Delta yhbC mutant cleared the organism from the liver and spleen 1 week faster than the parental strain and were able to develop specific serum IgG antibodies against the Delta yhbC mutant. PMID:18355292

  20. Inositol-Requiring Mutants of SACCHAROMYCES CEREVISIAE

    PubMed Central

    Culbertson, Michael R.; Henry, Susan A.

    1975-01-01

    Fifty-two inositol-requiring mutants of Saccharomyces cerevisiae were isolated following mutagenesis with ethyl methanesulfonate. Complementation and tetrad analysis revealed ten major complementation classes, representing ten independently segregating loci (designated ino1 through ino10) which recombined freely with their respective centromeres. Members of any given complementation class segregated as alleles of a single locus. Thirteen complementation subclasses were identified among thirty-six mutants which behaved as alleles of the ino1 locus. The complementation map for these mutants was circular.—Dramatic cell viability losses indicative of unbalanced growth were observed in liquid cultures of representative mutants under conditions of inositol starvation. Investigation of the timing, kinetics, and extent of cell death revealed that losses in cell viability in the range of 2-4 log orders could be prevented by the addition of inositol to the medium or by disruption of protein synthesis with cycloheximide. Mutants defective in nine of the ten loci identified in this study displayed these unusual characteristics. The results suggest an important physiological role for inositol that may be related to its cellular localization and function in membrane phospholipids. The possibility is discussed that inositol deficiency initiates the process of unbalanced growth leading to cell death through the loss of normal assembly, function, or integrity of biomembranes.—Part of this work has been reported in preliminary form (Culbertson and Henry 1974). PMID:1093935

  1. Escherichia coli mutants deficient in deoxyuridine triphosphatase.

    PubMed Central

    Hochhauser, S J; Weiss, B

    1978-01-01

    Mutants deficient in deoxyuridine triphosphatase (dUTPase) were identified by enzyme assays of randomly chosen heavily mutagenized clones. Five mutants of independent origin were obtained. One mutant produced a thermolabile enzyme, and it was presumed to have a mutation in the structural gene for dUTPase, designated dut. The most deficient mutant had the following associated phenotypes: less than 1% of parental dUTPase activity, prolonged generation time, increased sensitivity to 5'-fluorodeoxyuridine, increased rate of spontaneous mutation, increased rate of recombination (hyper-Rec), an inhibition of growth in the presence of 2 mM uracil, and a decreased ability to support the growth of phage P1 (but not T4 or lambda). This mutation also appeared to be incompatible with pyrE mutations. A revertant selected by its faster growth had regained dUTPase activity and lost its hyper-Rec phenotype. Many of the properties of the dut mutants are compatible with their presumed increased incorporation of uracil into DNA and the subsequent transient breakage of the DNA by excision repair. PMID:148458

  2. Phanerochaete mutants with enhanced ligninolytic activity

    SciTech Connect

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1993-06-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organopollutants in soils and aqueous media. Although some of the organic compounds are degraded under nonligninolytic conditions, most are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, biopulping, biobleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated or are hyperproducers or supersecretors of key enzymes under enriched conditions. Through ultraviolet-light and gamma-rays mutagenesis we have isolated a variety of mutants, some of which produce key enzymes of the ligninolytic system under high-nitrogen growth conditions. One of the mutants produced 272 units (U) of lignin peroxidases enzyme activity per liter after nine days under high nitrogen. The mutant and the parent strains produced up to 54 U/L and 62 U/L, respectively, of the enzyme activity under low-nitrogen growth conditions during this period. In some experiments the mutant showed 281 U/L of enzyme activity under high nitrogen after 17 days.

  3. Firefly Luciferase Mutants Allow Substrate-Selective Bioluminescence Imaging in the Mouse Brain.

    PubMed

    Adams, Spencer T; Mofford, David M; Reddy, G S Kiran Kumar; Miller, Stephen C

    2016-04-11

    Bioluminescence imaging is a powerful approach for visualizing specific events occurring inside live mice. Animals can be made to glow in response to the expression of a gene, the activity of an enzyme, or the growth of a tumor. But bioluminescence requires the interaction of a luciferase enzyme with a small-molecule luciferin, and its scope has been limited by the mere handful of natural combinations. Herein, we show that mutants of firefly luciferase can discriminate between natural and synthetic substrates in the brains of live mice. When using adeno-associated viral (AAV) vectors to express luciferases in the brain, we found that mutant luciferases that are inactive or weakly active with d-luciferin can light up brightly when treated with the aminoluciferins CycLuc1 and CycLuc2 or their respective FAAH-sensitive luciferin amides. Further development of selective luciferases promises to expand the power of bioluminescence and allow multiple events to be imaged in the same live animal. PMID:26991209

  4. Detection of (In)activity Periods in Human Body Motion Using Inertial Sensors: A Comparative Study

    PubMed Central

    Olivares, Alberto; Ramírez, Javier; Górriz, Juan M.; Olivares, Gonzalo; Damas, Miguel

    2012-01-01

    Determination of (in)activity periods when monitoring human body motion is a mandatory preprocessing step in all human inertial navigation and position analysis applications. Distinction of (in)activity needs to be established in order to allow the system to recompute the calibration parameters of the inertial sensors as well as the Zero Velocity Updates (ZUPT) of inertial navigation. The periodical recomputation of these parameters allows the application to maintain a constant degree of precision. This work presents a comparative study among different well known inertial magnitude-based detectors and proposes a new approach by applying spectrum-based detectors and memory-based detectors. A robust statistical comparison is carried out by the use of an accelerometer and angular rate signal synthesizer that mimics the output of accelerometers and gyroscopes when subjects are performing basic activities of daily life. Theoretical results are verified by testing the algorithms over signals gathered using an Inertial Measurement Unit (IMU). Detection accuracy rates of up to 97% are achieved. PMID:22778613

  5. Flavonoid-induced conversion of catalase to its inactive form--Compound II.

    PubMed

    Krych, J; Gebicki, J L; Gebicka, L

    2014-11-01

    Flavonoids (FlaOHs), plant polyphenols, are ubiquitous components of human diet and are known as antioxidants. However, their prooxidant activity has also been reported. We have recently found that FlaOHs inhibit catalase, the heme enzyme which catalyzes the decomposition of hydrogen peroxide (H2O2) into water and molecular oxygen. The catalytic cycle proceeds with the formation of the intermediate, Compound I (Cpd I), an oxoferryl porphyrin π-cation radical, the two-electron oxidation product of a heme group. Under conditions of low H2O2 fluxes and in the presence of an appropriate substrate, Cpd I can undergo one-electron reduction to inactive Compound II (Cpd II), oxoferryl derivative without radical site. Here we show that in vitro, under low fluxes of H2O2, FlaOHs reduce Cpd I to inactive Cpd II. Measurable amounts of Cpd II can be formed even in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) at concentration comparable with the investigated FlaOHs. Possible mechanisms of electron transfer from FlaOH molecule to the heme are discussed. PMID:25111015

  6. Active and Inactive Metabolic Pathways in Tumor Spheroids: Determination by GC-MS

    PubMed Central

    Hunnewell, Michael; Forbes, Neil S.

    2016-01-01

    Active metabolic pathways in three-dimensional cancer-cell cultures are potential chemotherapeutic targets that would be effective throughout tumors. Chaotic vasculature creates cellular regions in tumors with distinct metabolic behavior that are only present in aggregate cell masses. To quantify cancer cell metabolism, transformed mouse fibroblasts were grown as spheroids and fed isotopically labeled culture medium. Metabolite uptake and production rates were measured as functions of time. Gas chromatography - mass spectrometry was used quantify the extent of labeling on amino acids present in cytoplasmic extracts. The labeling pattern identified several active and inactive metabolic pathways: glutaminolysis was found to be active, and malic enzyme and gluconeogenesis were inactive. Transformed cells in spheroids were also found to actively synthesize serine, cysteine, alanine, aspartate, glutamate, and proline; and not synthesize glutamine. The activities of these pathways suggest that cancer cells consume glutamine for biosynthesis and not to provide cellular energy. Determining active metabolic pathways indicates how cells direct carbon flow and may lead to the discovery of novel molecular targets for anti-cancer therapy. PMID:20014107

  7. Cold-active alkaline phosphatase is irreversibly transformed into an inactive dimer by low urea concentrations.

    PubMed

    Hjörleifsson, Jens Guðmundur; Ásgeirsson, Bjarni

    2016-07-01

    Alkaline phosphatase is a homodimeric metallo-hydrolase where both Zn(2+) and Mg(2+) are important for catalysis and stability. Cold-adapted alkaline phosphatase variants have high activity at low temperatures and lower thermal stability compared with variants from mesophilic hosts. The instability, and thus inactivation, could be due to loose association of the dimers and/or loosely bound Mg(2)(+) in the active site, but this has not been studied in detail for the cold-adapted variants. Here, we focus on using the intrinsic fluorescence of Trp in alkaline phosphatase from the marine bacterium Vibrio splendidus (VAP) to probe for dimerization. Trp→Phe substitutions showed that two out of the five native Trp residues contributed mostly to the fluorescence emission. One residue, 15Å away from the active site (W460) and highly solvent excluded, was phosphorescent and had a distant role in substrate binding. An additional Trp residue was introduced to the dimer interface to act as a possible probe for dimerization. Urea denaturation curves indicated that an inactive dimer intermediate, structurally equivalent to the native state, was formed before dimer dissociation took place. This is the first example of the transition of a native dimer to an inactive dimer intermediate for alkaline phosphatase without using mutagenesis, ligands, or competitive inhibition. PMID:27043172

  8. Major initiatives related to childhood obesity and physical inactivity in Canada: the year in review.

    PubMed

    Tremblay, Mark S

    2012-01-01

    This manuscript briefly reviews 15 significant initiatives related to childhood obesity and physical inactivity in Canada between September 2010 and September 2011. These include the: announcement of a Federal-Provincial-Territorial framework for action to promote healthy weights; implementation of the nutrition labeling initiative; launch of the CBC "Live Right Now" campaign; announcement of the Public Health Agency of Canada's innovation strategy funding related to obesity; publication of the Canadian Health Measures Survey physical activity findings; release of new Canadian physical activity and sedentary behaviour guidelines; launch of ParticipACTION's "Think Again" campaign; workshop on building trust to address the epidemic of obesity; start of the Canadian Pediatric Weight Management Registry; initiation of "Our Health Our Future: A National Dialogue on Healthy Weights"; release of the Active Healthy Kids Canada Report Card on Physical Activity for Children and Youth; National Obesity Summit; Nature Play Day and Sports Day in Canada; development of the Canadian Assessment of Physical Literacy; and the creation of Active Canada 20/20--A National Physical Activity Plan. The diversity and intensity of activity addressing the childhood obesity and physical inactivity "epidemic" in Canada is encouraging and must be maintained and enhanced. PMID:22905632

  9. Imprinting control regions (ICRs) are marked by mono-allelic bivalent chromatin when transcriptionally inactive

    PubMed Central

    Maupetit-Méhouas, Stéphanie; Montibus, Bertille; Nury, David; Tayama, Chiharu; Wassef, Michel; Kota, Satya K.; Fogli, Anne; Cerqueira Campos, Fabiana; Hata, Kenichiro; Feil, Robert; Margueron, Raphael; Nakabayashi, Kazuhiko; Court, Franck; Arnaud, Philippe

    2016-01-01

    Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked by DNA methylation imprints on the maternal or paternal allele. Mono-allelic DNA methylation is strictly required for the process of imprinting and has to be faithfully maintained during the entire life-span. While the regulation of DNA methylation itself is well understood, the mechanisms whereby the opposite allele remains unmethylated are unclear. Here, we show that in the mouse, at maternally methylated ICRs, the paternal allele, which is constitutively associated with H3K4me2/3, is marked by default by H3K27me3 when these ICRs are transcriptionally inactive, leading to the formation of a bivalent chromatin signature. Our data suggest that at ICRs, chromatin bivalency has a protective role by ensuring that DNA on the paternal allele remains unmethylated and protected against spurious and unscheduled gene expression. Moreover, they provide the proof of concept that, beside pluripotent cells, chromatin bivalency is the default state of transcriptionally inactive CpG island promoters, regardless of the developmental stage, thereby contributing to protect cell identity. PMID:26400168

  10. Interaction of anammox bacteria and inactive methanogenic granules under high nitrogen selective pressure.

    PubMed

    Ni, Shou-Qing; Fessehaie, Anania; Lee, Po-Heng; Gao, Bao-Yu; Xu, Xing; Sung, Shihwu

    2010-09-01

    Granular anammox reactors usually adopted anaerobic/aerobic granules as source sludge, in which the washout of other species and enrichment of anammox biomass were very slow because of the competition of the coexisting bacteria. In this study, inactive methanogenic granules were proved to be suitable for rapid anammox granulation under high nitrogen concentrations by investigating their interaction with anammox bacteria. The start-up nitrite concentration was significantly higher than the published toxic level for anammox bacteria and other lab-scale studies. The nitrogen loading rate increased from 141 to 480 mg/L/d in 120 days operation with a total nitrogen removal efficiency of 96.0+/-0.6%. Anammox granules with a diameter of 1.3+/-0.4mm were observed over the course of three months. Molecular analysis showed that over 67% of the cells in the anammox granules were anammox bacteria after 90 days. The accommodations and proliferations of anammox bacteria in the inactive methanogenic granules might be the main reason for the high anammox purity in a short period. The important role of the extracellular polymer in the granule structure was observed via morphological observation. PMID:20444597

  11. The use of periodization in exercise prescriptions for inactive adults: A systematic review

    PubMed Central

    Strohacker, Kelley; Fazzino, Daniel; Breslin, Whitney L.; Xu, Xiaomeng

    2015-01-01

    Background Periodization of exercise is a method typically used in sports training, but the impact of periodized exercise on health outcomes in untrained adults is unclear. Purpose This review aims to summarize existing research wherein aerobic or resistance exercise was prescribed to inactive adults using a recognized periodization method. Methods A search of relevant databases, conducted between January and February of 2014, yielded 21 studies published between 2000 and 2013 that assessed the impact of periodized exercise on health outcomes in untrained participants. Results Substantial heterogeneity existed between studies, even under the same periodization method. Compared to baseline values or non-training control groups, prescribing periodized resistance or aerobic exercise yielded significant improvements in health outcomes related to traditional and emerging risk factors for cardiovascular disease, low-back and neck/shoulder pain, disease severity, and quality of life, with mixed results for increasing bone mineral density. Conclusions Although it is premature to conclude that periodized exercise is superior to non-periodized exercise for improving health outcomes, periodization appears to be a feasible means of prescribing exercise to inactive adults within an intervention setting. Further research is necessary to understand the effectiveness of periodizing aerobic exercise, the psychological effects of periodization, and the feasibility of implementing flexible non-linear methods. PMID:26844095

  12. Overweight, obesity, and inactivity and urban design in rapidly growing Chinese cities.

    PubMed

    Day, Kristen; Alfonzo, Mariela; Chen, Yufei; Guo, Zhan; Lee, Karen K

    2013-05-01

    China faces rising rates of overweight, obesity, and physical inactivity among its citizens. Risk is highest in China's rapidly growing cities and urban populations. Current urban development practices and policies in China heighten this risk. These include policies that support decentralization in land use planning; practices of neighborhood gating; and policies and practices tied to motor vehicle travel, transit planning, and bicycle and pedestrian infrastructure. In this paper, we review cultural, political, and economic issues that influence overweight, obesity, and inactivity in China. We examine key urban planning features and policies that shape urban environments that may compromise physical activity as part of everyday life, including walking and bicycling. We review the empirical research to identify planning and design strategies that support physical activity in other high-density cities in developing and developed countries. Finally, we identify successful strategies to increase physical activity in another growing, high-density city - New York City - to suggest strategies that may have relevance for rapidly urbanizing Chinese cities. PMID:23416231

  13. High prevalence of physical inactivity among adolescents living with HIV/AIDS

    PubMed Central

    Tanaka, Luana Fiengo; Latorre, Maria do Rosário Dias de Oliveira; da Silva, Aline Medeiros; Konstantyner, Thais Claudia Roma de Oliveira; Peres, Stela Verzinhasse; Marques, Heloisa Helena de Sousa

    2015-01-01

    Objective: To assess the prevalence of physical inactivity among adolescents with HIV/AIDS, as well as associated factors. Methods: Ninety-one adolescents (from 10 to 19 years old) with HIV/AIDS who are patients at a university follow-up service were interviewed. Anthropometric data (weight, height, and waist circumference) were measured twice; clinical information was obtained from medical records, and habitual physical activity was assessed by a questionnaire proposed by Florindo et al. The cutoff point for sedentariness was 300 minutes/week. Results: The prevalence of inadequate height for age, malnutrition, and overweight/obesity was 15.4%, 9.9% and 12.1%, respectively. The most common physical activities were soccer (44.4%), volleyball (14.4%) and cycling (7.8%). The median times spent with physical activity and walking/bicycling to school were 141 min and 39 min, respectively. Most adolescents (71.4%) were sedentary and this proportion was higher among girls (p=0.046). Conclusions: A high prevalence of physical inactivity among adolescents with HIV/AIDS was observed, similar to the general population. Promoting physical activity among adolescents, especially among girls with HIV/AIDS, as well as monitoring it should be part of the follow-up routine of these patients. PMID:25907024

  14. Any link between sexual inactivity and treadle pump performance characteristics: The Malawi case

    NASA Astrophysics Data System (ADS)

    Joseph, Chidanti-Malunga; Yamikani, Malunga

    In mitigating the effects of climate change in Malawi, government promotes the use of low cost irrigation technologies to small-scale farmers, especially in wetlands where water is available. The treadle pump is one such technology. The pump is a manual water lifting device operated by feet. Although the technology has been widely accepted by small-scale farmers, there are documented reports that some farmers abandon the technology, preferring other technologies such as river diversion. One theory for the abandonment is that female farmers claim that the technology makes their male counterparts sexually inactive. This research seeks to find an explanation to the misconception. The study analyzed the physical characteristics of the treadle pump and its users. The results show that the technology is male-dominated (30% were females out of a sample of 40). The results also show that the technology is labor-intensive with very small discharge rates (an average of 0.78 l/s) achieved regardless of the BMI of the operator. With such small discharge rates, in order to fulfill irrigation requirements of a crop, the operator has to pump for long hours. This exercise makes men naturally tired, perhaps making them sexually inactive as well.

  15. Heterometallic Triiron-Oxo/Hydroxo Clusters: Effect of Redox-Inactive Metals

    PubMed Central

    Herbert, David E.; Lionetti, Davide; Rittle, Jonathan; Agapie, Theodor

    2014-01-01

    A series of tetranuclear oxo/hydroxo clusters comprised of three Fe centers and a redox-inactive metal (M) of various charge is reported. Crystallographic studies show an unprecedented Fe3M(μ4-O)(μ2-OH) core that remains intact upon changing M or the oxidation state of iron. Electrochemical studies reveal that the reduction potentials (E1/2) span a window of 500 mV and depend upon the Lewis acidity of M. Using the pKa of the redox-inactive metal aqua complex as a measure of Lewis acidity, these compounds display a linear dependence between E1/2 and acidity with a slope of ca. 70 mV per pKa unit. The current study of [Fe3MO(OH)] and previous ones of [Mn3MOn] (n = 2, 4) moieties support the generality of the above relationship between the reduction potentials of heterometallic oxido clusters and the Lewis acidity of incorporated cations, as applied to clusters of different redox-active metals. PMID:24304416

  16. Structure of mutant human oncogene protein determined

    SciTech Connect

    Baum, R.

    1989-01-16

    The protein encoded by a mutant human oncogene differs only slightly in structure from the native protein that initiates normal cell division, a finding that may complicate efforts to develop inhibitors of the mutant protein. Previously, the x-ray structure of the protein encoded by the normal c-Ha-ras gene, a protein believed to signal cells to start or stop dividing through its interaction with guanosine triphosphate (GTP), was reported. The structure of the protein encoded by a transforming c-Ha-ras oncogene, in which a valine codon replaces the normal glycine codon at position 12 in the gene, has now been determined. The differences in the structures of the mutant and normal proteins are located primarily in a loop that interacts with the /beta/-phosphate of a bound guanosine diphosphate (GDP) molecule.

  17. Amphid defective mutant of Caenorhabditis elegans.

    PubMed

    De Riso, L; Ristoratore, F; Sebastiano, M; Bazzicalupo, P

    1994-01-01

    Studies are reported on a chemoreception mutant which arose in a mutator strain. The mutant sensory neurons do not stain with fluoresceine isothiocyanate (Dyf phenotype), hence the name, dyf-1, given to the gene it identifies. The gene maps on LGI, 0.4 map units from dpy-5 on the unc-11 side. The response of mutant worms to various repellents has been studied and shown to be partially altered. Other chemoreception based behaviors are less affected. The cilia of the sensory neurons of the amphid are shorter than normal and the primary defect may be in the capacity of the sheath cells to secrete the matrix material that fills the space between cilia in the amphid channel. Progress toward the molecular cloning of the gene is also reported. Relevant results from other laboratories are briefly reviewed. PMID:7896139

  18. High Persister Mutants in Mycobacterium tuberculosis.

    PubMed

    Torrey, Heather L; Keren, Iris; Via, Laura E; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  19. High Persister Mutants in Mycobacterium tuberculosis

    PubMed Central

    Torrey, Heather L.; Keren, Iris; Via, Laura E.; Lee, Jong Seok; Lewis, Kim

    2016-01-01

    Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip) mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection. PMID:27176494

  20. TOMATOMA: a novel tomato mutant database distributing Micro-Tom mutant collections.

    PubMed

    Saito, Takeshi; Ariizumi, Tohru; Okabe, Yoshihiro; Asamizu, Erika; Hiwasa-Tanase, Kyoko; Fukuda, Naoya; Mizoguchi, Tsuyoshi; Yamazaki, Yukiko; Aoki, Koh; Ezura, Hiroshi

    2011-02-01

    The tomato is an excellent model for studies of plants bearing berry-type fruits and for experimental studies of the Solanaceae family of plants due to its conserved genetic organization. In this study, a comprehensive mutant tomato population was generated in the background of Micro-Tom, a dwarf, rapid-growth variety. In this and previous studies, a family including 8,598 and 6,422 M(2) mutagenized lines was produced by ethylmethane sulfonate (EMS) mutagenesis and γ-ray irradiation, and this study developed and investigated these M(2) plants for alteration of visible phenotypes. A total of 9,183 independent M(2) families comprising 91,830 M(2) plants were inspected for phenotypic alteration, and 1,048 individual mutants were isolated. Subsequently, the observed mutant phenotypes were classified into 15 major categories and 48 subcategories. Overall, 1,819 phenotypic categories were found in 1,048 mutants. Of these mutants, 549 were pleiotropic, whereas 499 were non-pleiotropic. Multiple different mutant alleles per locus were found in the mutant libraries, suggesting that the mutagenized populations were nearly saturated. Additionally, genetic analysis of backcrosses indicated the successful inheritance of the mutations in BC(1)F(2) populations, confirming the reproducibility in the morphological phenotyping of the M(2) plants. To integrate and manage the visible phenotypes of mutants and other associated data, we developed the in silico database TOMATOMA, a relational system interfacing modules between mutant line names and phenotypic categories. TOMATOMA is a freely accessible database, and these mutant recourses are available through the TOMATOMA (http://tomatoma.nbrp.jp/index.jsp). PMID:21258066

  1. TOMATOMA: A Novel Tomato Mutant Database Distributing Micro-Tom Mutant Collections

    PubMed Central

    Saito, Takeshi; Ariizumi, Tohru; Okabe, Yoshihiro; Asamizu, Erika; Hiwasa-Tanase, Kyoko; Fukuda, Naoya; Mizoguchi, Tsuyoshi; Yamazaki, Yukiko; Aoki, Koh; Ezura, Hiroshi

    2011-01-01

    The tomato is an excellent model for studies of plants bearing berry-type fruits and for experimental studies of the Solanaceae family of plants due to its conserved genetic organization. In this study, a comprehensive mutant tomato population was generated in the background of Micro-Tom, a dwarf, rapid-growth variety. In this and previous studies, a family including 8,598 and 6,422 M2 mutagenized lines was produced by ethylmethane sulfonate (EMS) mutagenesis and γ-ray irradiation, and this study developed and investigated these M2 plants for alteration of visible phenotypes. A total of 9,183 independent M2 families comprising 91,830 M2 plants were inspected for phenotypic alteration, and 1,048 individual mutants were isolated. Subsequently, the observed mutant phenotypes were classified into 15 major categories and 48 subcategories. Overall, 1,819 phenotypic categories were found in 1,048 mutants. Of these mutants, 549 were pleiotropic, whereas 499 were non-pleiotropic. Multiple different mutant alleles per locus were found in the mutant libraries, suggesting that the mutagenized populations were nearly saturated. Additionally, genetic analysis of backcrosses indicated the successful inheritance of the mutations in BC1F2 populations, confirming the reproducibility in the morphological phenotyping of the M2 plants. To integrate and manage the visible phenotypes of mutants and other associated data, we developed the in silico database TOMATOMA, a relational system interfacing modules between mutant line names and phenotypic categories. TOMATOMA is a freely accessible database, and these mutant recourses are available through the TOMATOMA (http://tomatoma.nbrp.jp/index.jsp). PMID:21258066

  2. Characteristics of the Activity-Affect Association in Inactive People: An Ambulatory Assessment Study in Daily Life

    PubMed Central

    von Haaren, Birte; Loeffler, Simone Nadine; Haertel, Sascha; Anastasopoulou, Panagiota; Stumpp, Juergen; Hey, Stefan; Boes, Klaus

    2013-01-01

    Acute and regular exercise as well as physical activity (PA) is related to well-being and positive affect. Recent studies have shown that even daily, unstructured physical activities increase positive affect. However, the attempt to achieve adherence to PA or exercise in inactive people through public health interventions has often been unsuccessful. Most studies analyzing the activity-affect association in daily life, did not report participants’ habitual activity behavior. Thus, samples included active and inactive people, but they did not necessarily exhibit the same affective reactions to PA in daily life. Therefore the present study investigated whether the association between PA and subsequent affective state in daily life can also be observed in inactive individuals. We conducted a pilot study with 29 inactive university students (mean age 21.3 ± 1.7 years) using the method of ambulatory assessment. Affect was assessed via electronic diary and PA was measured with accelerometers. Participants had to rate affect every 2 h on a six item bipolar scale reflecting the three basic mood dimensions energetic arousal, valence, and calmness. We calculated activity intensity level [mean Metabolic Equivalent (MET) value] and the amount of time spent in light activity over the last 15 min before every diary prompt and conducted within-subject correlations. We did not find significant associations between activity intensity and the three mood dimensions. Due to the high variability in within-subject correlations we conclude that not all inactive people show the same affective reactions to PA in daily life. Analyzing the PA-affect association of inactive people was difficult due to little variance and distribution of the assessed variables. Interactive assessment and randomized controlled trials might help solving these problems. Future studies should examine characteristics of affective responses of inactive people to PA in daily life. General assumptions

  3. Escherichia coli mutants deficient in exonuclease VII.

    PubMed Central

    Chase, J W; Richardson, C C

    1977-01-01

    Mutants of Escherichia coli having reduced levels of exonuclease VII activity have been isolated by a mass screening procedure. Nine mutants, five of which are known to be of independent origin, were obtained and designated xse. The defects in these strains lie at two or more loci. One of these loci, xseA, lies in the interval between purG and purC; it is 93 to 97% co-transducible with guaA. The order of the genes in this region is purG-xseA guaA,B-purC. The available data do not allow xseA to be ordered with respect to guaA,B. Exonuclease VII purified from E. coli KLC3 xseA3 is more heat labile than exonuclease VII purified from the parent, E. coli PA610 xse+. Therefore, xseA is the structural gene for exonuclease VII. Mutants with defects in the xseA gene show increased sensitivity to nalidixic acid and have an abnormally high frequency of recombination (hyper-Rec phenotype) as measured by the procedure of Konrad and Lehlman (1974). The hyper-Rec character of xseA strains is approximately one-half that of the polAex1 mutant defective in the 5' leads to 3' hydrolytic activity of deoxyribonucleic acid polymerase I. The double mutant, polAex1 xseA7, is twice as hyper-Rec as the polAex1 mutant alone. The xseA- strains are slightly more sensitive to ultraviolet irradiation than the parent strain. Bacteriophages T7, fd, and lambdared grow normally in xseA- strains. Images PMID:320198

  4. Neurospora crassa mutants deficient in asparagine synthetase.

    PubMed Central

    MacPhee, K G; Nelson, R E; Schuster, S M

    1983-01-01

    Neurospora crassa mutants deficient in asparagine synthetase were selected by using the procedure of inositol-less death. Complementation tests among the 100 mutants isolated suggested that their alterations were genetically allelic. Recombination analysis with strain S1007t, an asparagine auxotroph, indicated that the mutations were located near or within the asn gene on linkage group V. In vitro assays with a heterokaryon indicated that the mutation was dominant. Thermal instability of cell extracts from temperature-sensitive strains in an in vitro asparagine synthetase assay determined that the mutations were in the structural gene(s) for asparagine synthetase. PMID:6137480

  5. Evolutionary Mutant Models for Human Disease

    PubMed Central

    Albertson, R. Craig; Cresko, William; Detrich, H. William; Postlethwait, John H.

    2010-01-01

    Although induced mutations in traditional laboratory animals have been valuable as models for human diseases, they have some important limitations. Here we propose a complementary approach to discover genes and mechanisms that might contribute to human disorders: the analysis of evolutionary mutant models whose adaptive phenotypes mimic maladaptive human diseases. If the type and mode of action of mutations favored by natural selection in wild populations are similar to those that contribute to human diseases, then studies in evolutionary mutant models have the potential to identify novel genetic factors and gene-by-environment interactions that affect human health and underlie human disease. PMID:19108930

  6. Proposed ionic bond between Arg300 and Glu270 and Glu271 are not involved in inactivation of a mutant firefly luciferase (LRR).

    PubMed

    Sobhani-Damavandifar, Zahra; Hosseinkhani, Saman; Sajedi, Reza H

    2016-05-01

    The weakness of firefly luciferase is its rapid inactivation. Many studies have been done to develop thermostable luciferases. One of these modifications was LRR mutant in which the Leu300 was substituted with Arg in the E(354)RR(356)Lampyris turkestanicus luciferase as template. LRR was more thermostable than the wild type but with only 0.02% activity. In this study, site-directed mutagenesis was used to change the proposed ionic bond between the Arg and two neighboring residues (Glu270 and Glu271), to understand if the induced interactions were responsible for inactivation in LRR. Our results showed that substitution of Glu270 and 271 with Ala removed the interactions but the activity of enzyme did not return. The E270A mutant was more active than LRR but the E271A and E270A/E271A mutants were inactive. Fluorescence and CD measurements showed that these mutations were accompanied by conformational changes. Extrinsic fluorescence measurement and obtained quenching data by KI and acrylamide also confirmed that the mutants were less compact than the LRR enzyme. In conclusion, in LRR, the interactions between Arg300 and Glu270 and Glu271 were not responsible for the enzyme inactivation and it is proposed that the enzyme inactivation is due to conformational changes of LRR mutant of firefly luciferase. PMID:26992788

  7. Antibodies to the extracellular receptor domain restore the hormone-insensitive kinase and conformation of the mutant insulin receptor valine 382.

    PubMed

    Lebrun, C; Baron, V; Kaliman, P; Gautier, N; Dolais-Kitabgi, J; Taylor, S; Accili, D; Van Obberghen, E

    1993-05-25

    A mutation substituting a valine for phenylalanine at residue 382 in the insulin receptor alpha-subunit has been found in two sisters with a genetic form of extreme insulin resistance. This receptor mutation impairs the ability of the hormone to activate autophosphorylation of solubilized receptors and phosphorylation of substrates (Accili, D., Mosthaf, L., Ullrich, A., and Taylor, S. I. (1991) J. Biol. Chem. 266, 434-439). We have previously demonstrated that in native receptors insulin induces a conformational change in the receptor beta-subunit, which is thought to be necessary for receptor activation (Baron, V., Gautier, N., Komoriya, A., Hainaut, P., Scimeca, J. C., Mervic, M., Lavielle, S., Dolais-Kitabgi, J., and Van Obberghen, E. (1990) Biochemistry 29, 4634-4641). Hence, it was thought that a defect in this conformational change might explain the functional defect of the mutant receptor. This appears to be the case, as we demonstrate here that the mutant receptor is locked in its inactive configuration. However, we found two monoclonal antibodies, directed to the extracellular domain, which are capable of restoring the mutant receptor kinase activity. The activation of the mutant receptor was accompanied by restoration of conformational changes in the beta-subunit C terminus. From these data, we draw the two following conclusions. (i) A causal link exists between receptor kinase activation and the occurrence of conformational changes. (ii) Ligands other than insulin, such as antibodies, which perturb the extracellular domain, can function as alternative ways to restore the mutant receptor kinase. PMID:8388389

  8. Physical inactivity prevalence and trends among Mexican adults: results from the National Health and Nutrition Survey (ENSANUT) 2006 and 2012

    PubMed Central

    2013-01-01

    Background Lifestyles such as unhealthy diets and the lack of physical activity have been contributed to the increased prevalence of obesity. In 2012, the world health organization published the first global recommendation for physical activity and health. People who do not meet at least 150 minutes of moderate-to-vigorous physical activity are considered to be physically inactive. The prevalence of physical inactivity worldwide is 31%, however there is insufficient data from prevalence and trends of physical inactivity in Mexican population. The purposes of this study are to describe the physical inactivity prevalence and recent trends in Mexican adults and to examine the association between physical inactivity with biologic and sociodemographic characteristics. Methods Representative samples of 17,183 and 10,729 adults (aged 20 to 69 years) who participated in the National Health and Nutrition Survey (ENSANUT) in 2006 and 2012, respectively. Moderate-to-vigorous physical activity (MVPA) was assessed using the short form version of the International Physical Activity Questionnaire (IPAQ), which was administered in face-to-face interviews. Self-reported IPAQ MVPA levels were adjusted using an equation derived from a previous validation study. Participants were considered inactive if they engaged in <150-minutes/week of moderate physical activity or <75 minutes/week of vigorous physical activity according to WHO classification criteria. Results The prevalence of physical inactivity was significantly higher in 2012 (19.4%, 95% CI: 18.1, 20.7) than in 2006 (13.4%, 95% CI: 12.5, 14.5). Adults in the obese category, 60–69 age group, and those in the highest socioeconomic status tertile were more likely to be physically inactive. Conclusions The proportion of the Mexican adult population who do not meet the minimum WHO physical activity criteria has increased by 6% points between 2006 and 2012. Given the increasing prevalence of obesity, the aging of the population

  9. Decreased intracellular survival of an fkpA mutant of Salmonella typhimurium Copenhagen.

    PubMed

    Horne, S M; Kottom, T J; Nolan, L K; Young, K D

    1997-02-01

    The fkpA gene of Salmonella typhimurium encodes a protein similar to the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Chlamydia trachomatis. Because Mip proteins enhance the ability of these intracellular pathogens to survive within macrophages and epithelial cells, we tested whether the product of the fkpA gene would have the same effect on the intracellular growth of a virulent strain of S. typhimurium. By a series of P22 transductions, the fkpA gene of S. typhimurium Copenhagen was replaced with the inactive fkpA1::omega-Cm gene from Escherichia coli, creating the mutant S. typhimurium KY32H1. The Copenhagen and KY32H1 strains were equally able to enter Caco-2 cells (an epithelial cell line) and J774.A1 cells (a macrophage-like cell line). However, compared to the parent, the fkpA mutant survived less well in both types of cells during the first 6 h after infection. The number of viable intracellular S. typhimurium Copenhagen bacteria remained constant 6 h after infection of Caco-2 cells, but the viability of S. typhimurium KY32H1 decreased significantly by 4 h postinfection. The fkpA mutant also exhibited a reduced ability to survive intracellularly in J774.A1 cells as little as 2 h postinfection. Complementation of the fkpA mutation by a plasmid-borne wild-type fkpA gene from E. coli restored the ability of S. typhimurium KY32H1 to grow normally in J774.A1 cells. Thus, expression of the mip-like fkpA gene confers on S. typhimurium Copenhagen properties analogous to those mediated by the Mip proteins in other intracellular pathogens, suggesting that this mechanism may play a role in the virulence and/or intracellular growth of numerous bacteria. PMID:9009347

  10. Mutants of Cytochrome P450 Reductase Lacking Either Gly-141 or Gly-143 Destabilize Its FMN Semiquinone.

    PubMed

    Rwere, Freeborn; Xia, Chuanwu; Im, Sangchoul; Haque, Mohammad M; Stuehr, Dennis J; Waskell, Lucy; Kim, Jung-Ja P

    2016-07-01

    NADPH-cytochrome P450 oxidoreductase transfers electrons from NADPH to cytochromes P450 via its FAD and FMN. To understand the biochemical and structural basis of electron transfer from FMN-hydroquinone to its partners, three deletion mutants in a conserved loop near the FMN were characterized. Comparison of oxidized and reduced wild type and mutant structures reveals that the basis for the air stability of the neutral blue semiquinone is protonation of the flavin N5 and strong H-bond formation with the Gly-141 carbonyl. The ΔGly-143 protein had moderately decreased activity with cytochrome P450 and cytochrome c It formed a flexible loop, which transiently interacts with the flavin N5, resulting in the generation of both an unstable neutral blue semiquinone and hydroquinone. The ΔGly-141 and ΔG141/E142N mutants were inactive with cytochrome P450 but fully active in reducing cytochrome c In the ΔGly-141 mutants, the backbone amide of Glu/Asn-142 forms an H-bond to the N5 of the oxidized flavin, which leads to formation of an unstable red anionic semiquinone with a more negative potential than the hydroquinone. The semiquinone of ΔG141/E142N was slightly more stable than that of ΔGly-141, consistent with its crystallographically demonstrated more rigid loop. Nonetheless, both ΔGly-141 red semiquinones were less stable than those of the corresponding loop in cytochrome P450 BM3 and the neuronal NOS mutant (ΔGly-810). Our results indicate that the catalytic activity of cytochrome P450 oxidoreductase is a function of the length, sequence, and flexibility of the 140s loop and illustrate the sophisticated variety of biochemical mechanisms employed in fine-tuning its redox properties and function. PMID:27189945

  11. Lack of enzyme activity in GBA2 mutants associated with hereditary spastic paraplegia/cerebellar ataxia (SPG46).

    PubMed

    Sultana, Saki; Reichbauer, Jennifer; Schüle, Rebecca; Mochel, Fanny; Synofzik, Matthis; van der Spoel, Aarnoud C

    2015-09-11

    Glucosylceramide is a membrane glycolipid made up of the sphingolipid ceramide and glucose, and has a wide intracellular distribution. Glucosylceramide is degraded to ceramide and glucose by distinct, non-homologous enzymes, including glucocerebrosidase (GBA), localized in the endolysosomal pathway, and β-glucosidase 2 (GBA2), which is associated with the plasma membrane and/or the endoplasmic reticulum. It is well established that mutations in the GBA gene result in endolysosomal glucosylceramide accumulation, which triggers Gaucher disease. In contrast, the biological significance of GBA2 is less well understood. GBA2-deficient mice present with male infertility, but humans carrying mutations in the GBA2 gene are affected with a combination of cerebellar ataxia and spastic paraplegia, as well as with thin corpus callosum and cognitive impairment (SPastic Gait locus #46, SPG46). To improve our understanding of the biochemical consequences of the GBA2 mutations, we have evaluated five nonsense and five missense GBA2 mutants for their enzyme activity. In transfected cells, the mutant forms of GBA2 were present in widely different amounts, ranging from overabundant to very minor, compared to the wild type enzyme. Nevertheless, none of the GBA2 mutant cDNAs raised the enzyme activity in transfected cells, in contrast to the wild-type enzyme. These results suggest that SPG46 patients have a severe deficit in GBA2 activity, because the GBA2 mutants are intrinsically inactive and/or reduced in amount. This assessment of the expression levels and enzyme activities of mutant forms of GBA2 offers a first insight in the biochemical basis of the complex pathologies seen in SPG46. PMID:26220345

  12. Crystal structure of a non-toxic mutant of heat-labile enterotoxin, which is a potent mucosal adjuvant.

    PubMed

    van den Akker, F; Pizza, M; Rappuoli, R; Hol, W G

    1997-12-01

    Two closely related bacterial toxins, heat-labile enterotoxin (LT-I) and cholera toxin (CT), not only invoke a toxic activity that affects many victims worldwide but also contain a beneficial mucosal adjuvant activity that significantly enhances the potency of vaccines in general. For the purpose of vaccine design it is most interesting that the undesirable toxic activity of these toxins can be eliminated by the single-site mutation Ser63Lys in the A subunit while the mucosal adjuvant activity is still present. The crystal structure of the Ser63Lys mutant of LT-I is determined at 2.0 A resolution. Its structure appears to be essentially the same as the wild-type LT-I structure. The substitution Ser63Lys was designed, based on the wild-type LT-I crystal structure, to decrease toxicity by interfering with NAD binding and/or catalysis. In the mutant crystal structure, the newly introduced lysine side chain is indeed positioned such that it could potentially obstruct the productive binding mode of the substrate NAD while at the same time its positive charge could possibly interfere with the critical function of nearby charged groups in the active site of LT-I. The fact that the Ser63Lys mutant of LT-I does not disrupt the wild-type LT-I structure makes the non-toxic mutant potentially suitable, from a structural point of view, to be used as a vaccine to prevent enterotoxigenic E. coli infections. The structural similarity of mutant and wild-type toxin might also be the reason why the inactive Ser63Lys variant retains its adjuvant activity. PMID:9416617

  13. Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms.

    PubMed

    Araki, Marito; Yang, Yinjie; Masubuchi, Nami; Hironaka, Yumi; Takei, Hiraku; Morishita, Soji; Mizukami, Yoshihisa; Kan, Shin; Shirane, Shuichi; Edahiro, Yoko; Sunami, Yoshitaka; Ohsaka, Akimichi; Komatsu, Norio

    2016-03-10

    Recurrent somatic mutations of calreticulin (CALR) have been identified in patients harboring myeloproliferative neoplasms; however, their role in tumorigenesis remains elusive. Here, we found that the expression of mutant but not wild-type CALR induces the thrombopoietin (TPO)-independent growth of UT-7/TPO cells. We demonstrated that c-MPL, the TPO receptor, is required for this cytokine-independent growth of UT-7/TPO cells. Mutant CALR preferentially associates with c-MPL that is bound to Janus kinase 2 (JAK2) over the wild-type protein. Furthermore, we demonstrated that the mutant-specific carboxyl terminus portion of CALR interferes with the P-domain of CALR to allow the N-domain to interact with c-MPL, providing an explanation for the gain-of-function property of mutant CALR. We showed that mutant CALR induces the phosphorylation of JAK2 and its downstream signaling molecules in UT-7/TPO cells and that this induction was blocked by JAK2 inhibitor treatment. Finally, we demonstrated that c-MPL is required for TPO-independent megakaryopoiesis in induced pluripotent stem cell-derived hematopoietic stem cells harboring the CALR mutation. These findings imply that mutant CALR activates the JAK2 downstream pathway via its association with c-MPL. Considering these results, we propose that mutant CALR promotes myeloproliferative neoplasm development by activating c-MPL and its downstream pathway. PMID:26817954

  14. The C-Terminus of Troponin T Is Essential for Maintaining the Inactive State of Regulated Actin

    PubMed Central

    Franklin, Andrew J.; Baxley, Tamatha; Kobayashi, Tomoyoshi; Chalovich, Joseph M.

    2012-01-01

    Striated muscle contraction is regulated by the actin binding proteins tropomyosin and troponin. Defects in these proteins lead to myopathies and cardiomyopathies. Deletion of the 14 C-terminal residues of cardiac troponin T leads to hypertrophic cardiomyopathy. We showed earlier that regulated actin containing Δ14 TnT was more readily activated than wild-type regulated actin. We suggested that the equilibria among the inactive (blocked), intermediate (closed or calcium), and active (open or myosin) states was shifted to the active state. We now show that, in addition, such regulated actin filaments cannot enter the inactive or blocked state. Regulated actin containing Δ14 TnT had ATPase activities in the absence of Ca2+ that were higher than wild-type filaments but far below the fully active rate. The rapid dissociation of S1-ATP from regulated actin filaments containing Δ14 TnT and acrylodan-labeled tropomyosin did not show the fluorescence increase characteristic of moving to the inactive state. Replacing wild-type TnI with S45E TnI, that favors the inactive state, did not restore the fluorescence change. We conclude that TnT has a previously unrecognized role in forming the inactive state of regulated actin. PMID:22713569

  15. [Inactive dumps in Santa Catarina's carboniferous area: analysis of risks to the public health and the environment].

    PubMed

    Possamai, Fernando Pagani; Viana, Ednilson; Schulz, Harry Edmar; de Costa, Marcel Madeira; Casagrande, Everson

    2007-01-01

    The existence of inactive dumps considerably increases the so-called "environmental liability"; so much so that the final destination of urban solid residues takes a prominent place on the list of environmental issues of societies(1). In the state of Santa Catarina, it can be said that, currently, the real conditions of the "final destination deposits", or simply the inactive dumps, is officially unknown. This is maybe most evident in the carboniferous area of the state that already suffers from the environmental impact of coal mining. This study attempts to make a survey of the inactive dumps in the carboniferous area of Santa Catarina, analysing the risks they represent to public health and to the environment. The results gathered show that, of the eleven municipal districts in the carboniferous area, nine have inactive dumps. In these nine districts, there are eleven inactive dumps that, according to the this evaluation, represent a large risk to public health and the environment when the parameters analysed are taken into acount. PMID:17680068

  16. Novel Two-Step Hierarchical Screening of Mutant Pools Reveals Mutants under Selection in Chicks.

    PubMed

    Yang, Hee-Jeong; Bogomolnaya, Lydia M; Elfenbein, Johanna R; Endicott-Yazdani, Tiana; Reynolds, M Megan; Porwollik, Steffen; Cheng, Pui; Xia, Xiao-Qin; McClelland, Michael; Andrews-Polymenis, Helene

    2016-04-01

    Contaminated chicken/egg products are major sources of human salmonellosis, yet the strategies used bySalmonellato colonize chickens are poorly understood. We applied a novel two-step hierarchical procedure to identify new genes important for colonization and persistence ofSalmonella entericaserotype Typhimurium in chickens. A library of 182S.Typhimurium mutants each containing a targeted deletion of a group of contiguous genes (for a total of 2,069 genes deleted) was used to identify regions under selection at 1, 3, and 9 days postinfection in chicks. Mutants in 11 regions were under selection at all assayed times (colonization mutants), and mutants in 15 regions were under selection only at day 9 (persistence mutants). We assembled a pool of 92 mutants, each deleted for a single gene, representing nearly all genes in nine regions under selection. Twelve single gene deletion mutants were under selection in this assay, and we confirmed 6 of 9 of these candidate mutants via competitive infections and complementation analysis in chicks.STM0580,STM1295,STM1297,STM3612,STM3615, andSTM3734are needed forSalmonellato colonize and persist in chicks and were not previously associated with this ability. One of these key genes,STM1297(selD), is required for anaerobic growth and supports the ability to utilize formate under these conditions, suggesting that metabolism of formate is important during infection. We report a hierarchical screening strategy to interrogate large portions of the genome during infection of animals using pools of mutants of low complexity. Using this strategy, we identified six genes not previously known to be needed during infection in chicks, and one of these (STM1297) suggests an important role for formate metabolism during infection. PMID:26857572

  17. Ethanol production using engineered mutant E. coli

    DOEpatents

    Ingram, Lonnie O.; Clark, David P.

    1991-01-01

    The subject invention concerns novel means and materials for producing ethanol as a fermentation product. Mutant E. coli are transformed with a gene coding for pyruvate decarboxylase activity. The resulting system is capable of producing relatively large amounts of ethanol from a variety of biomass sources.

  18. Phenotypic mutant library: potential for gene discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rapid development of high throughput and affordable Next- Generation Sequencing (NGS) techniques has renewed interest in gene discovery using forward genetics. The conventional forward genetic approach starts with isolation of mutants with a phenotype of interest, mapping the mutation within a s...

  19. Rapid Antibiotic Resistance Evolution of GASP Mutants

    NASA Astrophysics Data System (ADS)

    Zhang, Qiucen; Kim, Hyunsung; Pourmand, Nader; Austin, Robert

    2012-02-01

    The GASP phenotype in bacteria is due to a mutation which enables the bacteria to grow under high stress conditions where other bacteria stop growing. We probe using our Death Galaxy microenvironment how rapidly the GASP mutant can evolve resistance to mutagenic antibiotics compared to wild-type bacteria, and explore the genomic landscape changes due to the evolution of resistance.

  20. Yeast mutants overproducing iso-cytochromes c

    SciTech Connect

    Sherman, F.; Cardillo, T.S.; Errede, B.; Friedman, L.; McKnight, G.; Stiles, J.I.

    1980-01-01

    For over 15 years, the iso-cytochrome c system in the yeast Saccharomyces cerevisiae has been used to investigate a multitude of problems in genetics and molecular biology. More recently, attention has been focused on using mutants for examining translation and transcriptional processes and for probing regulatory regions governing gene expression. In an effort to explore regulatory mechanisms and to investigate mutational alterations that lead to increased levels of gene products, we have isolated and characterized mutants that overproduce cytochrome c. In this paper we have briefly summarized background information of some essential features of the iso-cytochrome c system and we have described the types of mutants that overproduce iso-1-cytochrome c or iso-2-cytochrome c. Genetic procedures and recombinant DNA procedures were used to demonstrate that abnormally high amounts of gene products occur in mutants as result of duplications of gene copies or of extended alteration of regulatory regions. The results summarized in this paper point out the requirements of gross mutational changes or rearrangements of chromosomal segments for augmenting gene products.

  1. Genotyping-by-sequencing of glossy mutants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glossy mutants are a common occurrence in Brassica oleracea L. and they have been documented in most crop varieties of the species including cabbage, kale, broccoli, and collard. Glossy phenotypes have been of particular interest to researchers due to observations that they influence insect behavior...

  2. Quantitative genetics and utilization of mutants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relatively low level of genetic variability currently available in cotton makes mutagenesis attractive to overcome this problem. Mutations can occur either spontaneously or be induced. The majority of the genes we use today are spontaneous mutants that developed over a long period of time. Induc...

  3. Radiological survey of the inactive uranium-mill tailings at Durango, Colorado

    SciTech Connect

    Haywood, F.F.; Perdue, P.T.; Shinpaugh, W.H.; Ellis, B.S.; Chou, K.D.

    1980-03-01

    Results of a radiological survey of the inactive uranium-mill site at Durango, Colorado, conducted in April 1976, in cooperation with a team from Ford, Bacon and Davis Utah Inc., are presented together with descriptions of the instruments and techniques used to obtain the data. Direct above-ground gamma measurements and analysis of surface soil and sediment samples indicate movement of tailings from the piles toward Lightner Creek on the north and the Animas River on the east side of the piles. The concentration of /sup 226/Ra in the former raffinate pond area is only slightly above the background level. Two structures in Durango were found to contain high concentrations of airborne radon daughters, where tailings are known to have been utilized in construction. Near-background concentrations of radon daughters were found in a well-ventilated building close to the tailings.

  4. Inactive dry yeast application on grapes modify Sauvignon Blanc wine aroma.

    PubMed

    Šuklje, Katja; Antalick, Guillaume; Buica, Astrid; Coetzee, Zelmari A; Brand, Jeanne; Schmidtke, Leigh M; Vivier, Melané A

    2016-04-15

    This study investigated the potential to improve wine aroma by applying two inactive dry yeast products (IDYs) at the onset of ripening on Sauvignon Blanc grapes. Both products led to increased reduced glutathione concentrations in the grape juice and corresponding wines, as well as differences in individual higher alcohol acetates (HAAs) and ethyl esters of straight chain fatty acids (EEFAs) at the end of fermentation. After two months of storage, a significantly slower decrease of EEFAs and to a lesser extent of HAAs was found for wines made from grapes with IDY applications. These wines also resulted in significantly slower synthesis of ethyl esters of branched acids, whereas varietal thiols were altered in a product-specific manner. The modifications in the wine chemical composition were also sensorially corroborated. This study showed that vineyard additions of IDY products directly on the grapes at the onset of ripening have a subsequent benefit to the production and preservation of aroma in wines. PMID:26675843

  5. Radiological survey of the inactive uranium-mill tailings at Rifle, Colorado

    SciTech Connect

    Haywood, F.F.; Jacobs, D.J.; Ellis, B.S.; Hubbard, H.M. Jr.; Shinpaugh, W.H.

    1980-06-01

    Results of radiological surveys of two inactive uranium-mill sites near Rifle, Colorado, in May 1976 are presented. These sites are referred to as Old Rifle and New Rifle. The calculated /sup 226/Ra inventory of the latter site is much higher than at the older mill location. Data on above-ground measurements of gamma exposure rates, surface and near-surface concentration of /sup 226/Ra in soil and sediment samples, concentration of /sup 226/Ra in water, calculated subsurface distribution of /sup 226/Ra, and particulate radionuclide concentrations in air samples are given. The data serve to define the extent of contamination in the vicinity of the mill sites and their immediate surrounding areas with tailings particles. Results of these measurements were utilized as technical input for an engineering assessment of these two sites.

  6. Conformationally restricted elongation factor G retains GTPase activity but is inactive in translocation on the ribosome.

    PubMed

    Peske, F; Matassova, N B; Savelsbergh, A; Rodnina, M V; Wintermeyer, W

    2000-08-01

    Elongation factor G (EF-G) from Escherichia coli is a large, five-domain GTPase that promotes tRNA translocation on the ribosome. Full activity requires GTP hydrolysis, suggesting that a conformational change of the factor is important for function. To restrict the intramolecular mobility, two cysteine residues were engineered into domains 1 and 5 of EF-G that spontaneously formed a disulfide cross-link. Cross-linked EF-G retained GTPase activity on the ribosome, whereas it was inactive in translocation as well as in turnover. Both activities were restored when the cross-link was reversed by reduction. These results strongly argue against a GTPase switch-type model of EF-G function and demonstrate that conformational mobility is an absolute requirement for EF-G function on the ribosome. PMID:10983996

  7. Radiological survey of the inactive uranium-mill tailings at Gunnison, Colorado

    SciTech Connect

    Haywood, F.F.; Jacobs, D.G.; Hubbard, H.M. Jr.; Ellis, B.S.; Shinpaugh, W.H.

    1980-03-01

    The findings of a radiological survey of the inactive uranium-mill site at Gunnison, Colorado, conducted in May 1976, are presented. Results of surface soil sample analyses and direct gamma radiation measurements indicate limited spread of tailings off the site. The only significant above background measurements off the site were obtained in an area previously covered by the tailings pile. There was little evidence of contamination of the surface or of unconfined groundwater in the vicinity of the tailings pile; however, the hydrologic conditions at the site indicate a potential for such contamination. The concentration of /sup 226/Ra in all water samples except one from the tailings pile was well below the concentration guide for drinking water. The subsurface distribution of /sup 226/Ra in 14 bore holes located on and around the tailings pile was calculated from gamma ray monitoring data obtained jointly with Ford, Bacon and Davis Utah Inc.

  8. Hazardous waste site assessment: Inactive landfill, Site 300, Lawrence Livermore National Laboratory

    SciTech Connect

    Not Available

    1985-01-01

    This report presents the results of an investigation of an inactive landfill (Pit 6) at Lawrence Livermore National Laboratory's (LLNL) Site 300. The primary objectives were to: collect and review background information pertaining to past waste disposal practices and previous environmental characterization studies; conduct a geophysical survey of the landfill area to locate the buried wastes; conduct a hydrogeologic investigation to provide additional data on the rate and direction of groundwater flow, the extent of any groundwater contamination, and to investigate the connection, if any, of the shallow groundwater beneath the landfill with the local drinking water supply; conduct a risk assessment to identify the degree of threat posed by the landfill to the public health and environment; compile a preliminary list of feasible long-term remedial action alternatives for the landfill; and develop a list of recommendations for any interim measures necessary at the landfill should the long-term remedial action plan be needed.

  9. Sampling and Analysis Plan for Flammable Gases in Inactive Miscellaneous Underground Storage Tanks

    SciTech Connect

    NGUYEN, D.M.

    2000-02-01

    This sampling and analysis plan (SAP) identifies the field measurements for a screening of flammable gases in the vapor space of the inactive miscellaneous underground storage tanks (IMUSTs) currently assigned to the River Protection Project (RPP). If a measurement exceeds 25% of the lower flammability limit (LFL), vapor grab samples will be collected for laboratory analysis. This SAP also specifies the sample collection, laboratory analysis, quality assurance/quality control (QA/QC), and reporting objectives for grab sampling. Technical bases for the sampling objectives are provided in the Tank Safety Screening Data Quality Objectives (Dukelow et al 1995). The screening data will be used to determine if additional data are needed to support closure of a flammable gas unreviewed safety question for these facilities.

  10. Physiology of Fluid and Electrolyte Responses During Inactivity: Water Immersion and Bed Rest

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    1984-01-01

    This manuscript emphasizes the physiology of fluid-electrolyte-hormonal responses during the prolonged inactivity of bed rest and water immersion. An understanding of the total mechanism of adaptation (deconditioning) should provide more insight into the conditioning process. Findings that need to be confirmed during bed rest and immersion are: (1) the volume and tissues of origin of fluid shifted to the thorax and head; (2) interstitial fluid pressure changes in muscle and subcutaneous tissue, particularly during immersion; and (3) the composition of the incoming presumably interstitial fluid that contributes to the early hypervolemia. Better resolution of the time course and source of the diuretic fluid is needed. Important data will be forthcoming when hypotheses are tested involving the probable action of the emerging diuretic and natriuretic hormones, between themselves and among vasopressin and aldosterone, on diuresis and blood pressure control.

  11. The development of social capital through football and running: studying an intervention program for inactive women.

    PubMed

    Ottesen, L; Jeppesen, R S; Krustrup, B R

    2010-04-01

    This article examines the development of social capital through the use and dynamics of different types of stories ("I,"we" and "they") as described by Robert D. Putnam. The data come from a research project in which inactive women participated in a 16-week intervention program of physical exercise, either in the form of football or running. The study shows a positive development of social capital in the two different types of physical activity. The I-stories show themselves to be central to bonding within the two groups and bridging outside the groups (developing and/or creating networks). The study also points to the importance of the activity itself for internal bonding illustrated through we- and they-stories. Our data indicate that team sports, such as football, may have an advantage over individual sports in the development of social capital. PMID:20546546

  12. The inactive-active phase transition in the noisy additive (exclusive-or) probabilistic cellular automaton

    NASA Astrophysics Data System (ADS)

    Mendonça, J. Ricardo G.

    2016-07-01

    We investigate the inactive-active phase transition in an array of additive (exclusive-or) cellular automata (CA) under noise. The model is closely related with the Domany-Kinzel (DK) probabilistic cellular automaton (PCA), for which there are rigorous as well as numerical estimates on the transition probabilities. Here, we characterize the critical behavior of the noisy additive cellular automaton by mean field analysis and finite-size scaling and show that its phase transition belongs to the directed percolation universality class of critical behavior. As a by-product of our analysis, we argue that the critical behavior of the noisy elementary CA 90 and 102 (in Wolfram’s enumeration scheme) must be the same. We also perform an empirical investigation of the mean field equations to assess their quality and find that away from the critical point (but not necessarily very far away) the mean field approximations provide a reasonably good description of the dynamics of the PCA.

  13. Revegetation/rock cover for stabilization of inactive uranium mill tailings disposal sites

    SciTech Connect

    Beedlow, P.A.; McShane, M.C.; Cadwell, L.L.

    1982-07-01

    Pacific Northwest Laboratory is developing design and performance guidelines for surface stabilization of inactive uranium mill tailings. In this work, vegetation and rock covers are being evaluated for maintaining long-term integrity of impoundment systems. Methods are being developed to estimate erosion rates associated with rock and/or vegetation covers, and to determine the effects of surface treatments on soil moisture. Interactions between surface treatments and barriers (radon and biological) are being studied as well. The product will be a set of guidelines to aid in designing surface covers. This report presents the status of this program and a discussion of considerations pertinent to the application of surface covers to tailings. Test plots located in Grand Junction, Colorado and Waterflow, New Mexico are being used to study: (1) the interactions between vegetation and radon and biological barriers, (2) the effects of surface covers on soil moisture, and (3) the effects of rock covers on vegetation.

  14. Assessment of the radiological impact of the inactive uranium-mill tailings at Mexican Hat, Utah

    SciTech Connect

    Haywood, F.F.; Goldsmith, W.A.; Ellis, B.S.; Hubbard, H.M. Jr.; Fox, W.F.; Shinpaugh, W.H.

    1980-03-01

    High surface soil concentrations of /sup 226/Ra and high above-ground measurements of gamma-ray intensity in the vicinity of the inactive uranium-mill tailings at Mexican Hat show both wind and water erosion of the tailings. The former mill area, occupied by a trade school at the time of this survey, shows a comparatively high level of contamination, probably from unprocessed ore on the surface of the ore storage area near the location of the former mill buildings. However, the estimated health effect of exposure to gamma rays during a 2000-hr work year in the area represents an increase of 0.1% in the risk of death from cancer. Exposure of less than 600 persons within 1.6 km of the tailings to radon daughters results in an estimated 0.2%/year increase in risk of lung cancer.

  15. Transition from physical activity to inactivity increases skeletal muscle miR-148b content and triggers insulin resistance.

    PubMed

    Gastebois, Caroline; Chanon, Stéphanie; Rome, Sophie; Durand, Christine; Pelascini, Elise; Jalabert, Audrey; Euthine, Vanessa; Pialoux, Vincent; Blanc, Stéphane; Simon, Chantal; Lefai, Etienne

    2016-09-01

    This study investigated miR-148b as a potential physiological actor of physical inactivity-induced effects in skeletal muscle. By using animal and human protocols, we demonstrated that the early phase of transition toward inactivity was associated with an increase in muscle miR-148b content, which triggered the downregulation of NRAS and ROCK1 target genes. Using human myotubes, we demonstrated that overexpression of miR-148b decreased NRAS and ROCK1 protein levels, and PKB phosphorylation and glucose uptake in response to insulin. Increase in muscle miR-148b content might thus participate in the decrease in insulin sensitivity at the whole body level during the transition toward physical inactivity. PMID:27597765

  16. Flow-mediated dilation in the inactive limb following acute hypoxic exercise.

    PubMed

    Katayama, Keisho; Yamashita, Shin; Iwamoto, Erika; Ishida, Koji

    2016-01-01

    The purpose of this study was to elucidate the effect of acute aerobic exercise performed under hypoxic conditions on flow-mediated dilation (FMD) in the inactive limb. Seven males participated in the study. The subjects performed two submaximal leg cycling on a semirecumbent ergometer at the same relative intensity (60% peak oxygen uptake) in normoxia [inspired oxygen fraction (FIO2) = 0·21] and hypoxia (FIO2 = 0·12-0·13) for 30 min. The brachial artery diameter and blood velocity during exercise were measured via ultrasound, and the antegrade and retrograde shear rates were calculated. Before and 5, 30 and 60 min after exercise, brachial artery FMD was measured in normoxia. FMD was estimated as the percentage increase in peak diameter from the baseline diameter at prior occlusion (%FMD) and as the controlling changes in baseline diameter (the corrected-%FMD). No difference in antegrade shear rate during exercise was detected between the normoxic and hypoxic conditions, whereas the retrograde shear rate was larger during hypoxic exercise. The %FMD decreased significantly at 5 min after exercise in both normoxia and hypoxia, and it returned to pre-exercise levels within 60 min of recovery. Significant decreases in FMD at 5 min after exercise had disappeared when the baseline diameter was controlled using an analysis of covariance (the corrected-%FMD). No significant differences were observed between the normoxic and hypoxic trials in the %FMD and corrected-%FMD following exercise. These results suggest that hypoxia has no impact on endothelial function in the inactive limb following acute aerobic exercise. PMID:25257848

  17. Nutritional status and physical inactivity in moderated asthmatics: A pilot study.

    PubMed

    Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

    2016-08-01

    Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity.Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants.FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12).This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening. PMID:27495092

  18. Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

    PubMed Central

    Streeter, K.A.; Baker-Herman, T.L.

    2014-01-01

    Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

  19. Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation.

    PubMed

    Streeter, K A; Baker-Herman, T L

    2014-06-01

    Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

  20. Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

    PubMed

    Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

    2016-06-01

    Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. PMID:27067618

  1. The Prevalence and Incidence of Epiretinal Membranes in Eyes With Inactive Extramacular CMV Retinitis

    PubMed Central

    Kozak, Igor; Vaidya, Vijay; Van Natta, Mark L.; Pak, Jeong W.; May, K. Patrick; Thorne, Jennifer E.

    2014-01-01

    Purpose. To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS). Methods. A case–control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios. Results. The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5–17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2–27.9) (P < 0.01). Conclusions. A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients. PMID:24925880

  2. Short term aerobic exercise alters the reinforcing value of food in inactive adults.

    PubMed

    Panek, Leah M; Jones, Kelly R; Temple, Jennifer L

    2014-10-01

    Motivation to eat, or the reinforcing value of food, may be influenced by a number of factors, including physical activity. The purpose of these studies was to test the hypothesis that short-term moderate-vigorous intensity aerobic exercise would alter the reinforcing value of high (HED) and low (LED) energy density foods in inactive adults. The reinforcing value of LED and HED food was measured at baseline and again after two weeks of aerobic exercise. In Experiment 1, 41 participants were randomized to a no exercise condition or aerobic exercise for 3 days per week for two weeks. In Experiment 2, 76 participants were randomized to one of four aerobic exercise frequencies, 0, 1, 3, or 5 days per week for two weeks. In both experiments, exercise reduced the reinforcing value of HED food compared to baseline and to non-exercise controls. In Experiment 2, the 5 day group also showed a significant increase in the reinforcing value of LED food compared to baseline and other exercise frequencies. Liking of HED and LED foods and consumption of HED food were not affected by exercise treatment. Finally, in Experiment 2, the 5 day group reported consuming more energy outside of the laboratory than the other groups. Taken together, these data suggest, in inactive individuals, motivation to obtain HED and LED foods can be altered with a short-term moderate-vigorous intensity exercise intervention. Further research is needed to understand the cognitive and physiological processes involved in food choices paired with exercise. PMID:24996592

  3. mHealth Physical Activity Intervention: A Randomized Pilot Study in Physically Inactive Pregnant Women.

    PubMed

    Choi, JiWon; Lee, Ji Hyeon; Vittinghoff, Eric; Fukuoka, Yoshimi

    2016-05-01

    Introduction Physical inactivity is prevalent in pregnant women, and innovative strategies to promote physical activity are strongly needed. The purpose of the study was to test a 12-week mobile health (mHealth) physical activity intervention for feasibility and potential efficacy. Methods Participants were recruited between December 2012 and February 2014 using diverse recruitment methods. Thirty pregnant women between 10 and 20 weeks of gestation were randomized to an intervention (mobile phone app plus Fitbit) or a control (Fitbit) group. Both conditions targeted gradual increases in physical activity. The mHealth intervention included daily messages and a mobile phone activity diary with automated feedback and self-monitoring systems. Results On monthly average, 4 women were screened for initial eligibility by telephone and 2.5 were randomized. Intervention participants had a 1096 ± 1898 step increase in daily steps compared to an increase of 259 ± 1604 steps in control participants at 12 weeks. The change between groups in weekly mean steps per day during the 12-week study period was not statistically significant (p = 0.38). The intervention group reported lower perceived barrier to being active, lack of energy, than the control group at 12-week visit (p = 0.02). The rates of responding to daily messages and using the daily diary through the mobile app declined during the 12 week study period. Discussion It was difficult to recruit and randomize inactive women who wanted to increase physical activity during pregnancy. Pregnant women who were motivated to increase physical activity might find using mobile technologies in assessing and promoting PA acceptable. Possible reasons for the non-significant treatment effect of the mHealth intervention on physical activity are discussed. Public awareness of safety and benefits of physical activity during pregnancy should be promoted. Clinicaltrials.Gov Identifier NCT01461707. PMID:26649879

  4. Metabolic rates and biochemical compositions of Apostichopus japonicus (Selenka) tissue during periods of inactivity

    NASA Astrophysics Data System (ADS)

    Bao, Jie; Dong, Shuanglin; Tian, Xiangli; Wang, Fang; Gao, Qinfeng; Dong, Yunwei

    2010-03-01

    Estivation, hibernation, and starvation are indispensable inactive states of sea cucumbers Apostichopus japonicus in nature and in culture ponds. Generally, temperature is the principal factor that induces estivation or hibernation in the sea cucumber. The present study provided insight into the physiological adaptations of A. japonicus during the three types of inactivity (hibernation, estivation, and starvation) by measuring the oxygen consumption rates ( Vo2) and biochemical compositions under laboratory conditions of low (3°C), normal (17°C) and high (24°C) temperature. The results show that the characteristics of A. japonicus in dormancy (hibernation and estivation) states were quite different from higher animals, such as fishes, amphibians, reptiles, and mammals, but more closely resembled a semi-dormant state. It was observed that the shift in the A. japonicus physiological state from normal to dormancy was a chronic rather than acute process, indicated by the gradual depression of metabolic rate. While metabolic rates declined 44.9% for the estivation group and 71.7% for the hibernation group, relative to initial rates, during the 36 d culture period, metabolic rates were not maintained at constant levels during these states. The metabolic depression processes for sea cucumbers in hibernation and estivation appeared to be a passive and an active metabolic suppression, respectively. In contrast, the metabolic rates (128.90±11.70 μg/g h) of estivating sea cucumbers were notably higher (107.85±6.31 μg/g h) than in starving sea cucumbers at 17°C, which indicated that the dormancy mechanism here, as a physiological inhibition, was not as efficient as in higher animals. Finally, the principle metabolic substrate or energy source of sea cucumbers in hibernation was lipid, whereas in estivation they mainly consumed protein in the early times and both protein and lipid thereafter.

  5. Clinical joint inactivity predicts structural stability in patients with established rheumatoid arthritis

    PubMed Central

    Gärtner, M; Sigmund, I K; Alasti, F; Supp, G; Radner, H; Machold, K; Smolen, J S; Aletaha, D

    2016-01-01

    Objectives Clinical joint activity is a strong predictor of joint damage in rheumatoid arthritis (RA), but progression of damage might increase despite clinical inactivity of the respective joint (silent progression). The aim of this study was to evaluate the prevalence of silent joint progression, but particularly on the patient level and to investigate the duration of clinical inactivity as a marker for non-progression on the joint level. Methods 279 patients with RA with any radiographic progression over an observational period of 3–5 years were included. We obtained radiographic and clinical data of 22 hand/finger joints over a period of at least 3 years. Prevalence of silent progression and associations of clinical joint activity and radiographic progression were evaluated. Results 120 (43.0%) of the patients showed radiographic progression in at least one of their joints without any signs of clinical activity in that respective joint. In only 7 (5.8%) patients, such silent joint progression would go undetected, as the remainder had other joints with clinical activity, either with (n=84; 70.0%) or without (n=29; 24.2%) accompanying radiographic progression. Also, the risk of silent progression decreases with duration of clinical activity. Conclusions Silent progression of a joint without accompanying apparent clinical activity in any other joint of a patient was very rare, and would therefore be most likely detected by the assessment of the patient. Thus, full clinical remission is an excellent marker of structural stability in patients with RA, and the maintenance of this state reduces the risk of progression even further. PMID:27110386

  6. Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa

    PubMed Central

    Bergen, Phillip J.; Li, Jian; Rayner, Craig R.; Nation, Roger L.

    2006-01-01

    There is a dearth of information on the pharmacodynamics of “colistin,” despite its increasing use as a last line of defense for treatment of infections caused by multidrug-resistant gram-negative organisms. The antimicrobial activities of colistin and colistin methanesulfonate (CMS) were investigated by studying the time-kill kinetics of each against a type culture of Pseudomonas aeruginosa in cation-adjusted Mueller-Hinton broth. The appearance of colistin from CMS spiked at 8.0 and 32 mg/liter was measured by high-performance liquid chromatography, which generated colistin concentration-time profiles. These concentration-time profiles were subsequently mimicked in other incubations, independent of CMS, by incrementally spiking colistin. When the cultures were spiked with CMS at either concentration, there was a substantial delay in the onset of the killing effect which was not evident until the concentrations of colistin generated from the hydrolysis of CMS had reached approximately 0.5 to 1 mg/liter (i.e., ∼0.5 to 1 times the MIC for colistin). The time course of the killing effect was similar when colistin was added incrementally to achieve the same colistin concentration-time course observed from the hydrolysis of CMS. Given that the killing kinetics of CMS can be accounted for by the appearance of colistin, CMS is an inactive prodrug of colistin with activity against P. aeruginosa. This is the first study to demonstrate the formation of colistin in microbiological media containing CMS and to demonstrate that CMS is an inactive prodrug of colistin. These findings have important implications for susceptibility testing involving “colistin,” in particular, for MIC measurement and for microbiological assays and pharmacokinetic and pharmacodynamic studies. PMID:16723551

  7. Life and Death of Deep-Sea Vents: Bacterial Diversity and Ecosystem Succession on Inactive Hydrothermal Sulfides

    PubMed Central

    Sylvan, Jason B.; Toner, Brandy M.; Edwards, Katrina J.

    2012-01-01

    ABSTRACT Hydrothermal chimneys are a globally dispersed habitat on the seafloor associated with mid-ocean ridge (MOR) spreading centers. Active, hot, venting sulfide structures from MORs have been examined for microbial diversity and ecology since their discovery in the mid-1970s, and recent work has also begun to explore the microbiology of inactive sulfides—structures that persist for decades to millennia and form moderate to massive deposits at and below the seafloor. Here we used tag pyrosequencing of the V6 region of the 16S rRNA and full-length 16S rRNA sequencing on inactive hydrothermal sulfide chimney samples from 9°N on the East Pacific Rise to learn their bacterial composition, metabolic potential, and succession from venting to nonventing (inactive) regimes. Alpha-, beta-, delta-, and gammaproteobacteria and members of the phylum Bacteroidetes dominate all inactive sulfides. Greater than 26% of the V6 tags obtained are closely related to lineages involved in sulfur, nitrogen, iron, and methane cycling. Epsilonproteobacteria represent <4% of the V6 tags recovered from inactive sulfides and 15% of the full-length clones, despite their high abundance in active chimneys. Members of the phylum Aquificae, which are common in active vents, were absent from both the V6 tags and full-length 16S rRNA data sets. In both analyses, the proportions of alphaproteobacteria, betaproteobacteria, and members of the phylum Bacteroidetes were greater than those found on active hydrothermal sulfides. These shifts in bacterial population structure on inactive chimneys reveal ecological succession following cessation of venting and also imply a potential shift in microbial activity and metabolic guilds on hydrothermal sulfides, the dominant biome that results from seafloor venting. PMID:22275502

  8. Life and death of deep-sea vents: bacterial diversity and ecosystem succession on inactive hydrothermal sulfides.

    PubMed

    Sylvan, Jason B; Toner, Brandy M; Edwards, Katrina J

    2012-01-01

    Hydrothermal chimneys are a globally dispersed habitat on the seafloor associated with mid-ocean ridge (MOR) spreading centers. Active, hot, venting sulfide structures from MORs have been examined for microbial diversity and ecology since their discovery in the mid-1970s, and recent work has also begun to explore the microbiology of inactive sulfides--structures that persist for decades to millennia and form moderate to massive deposits at and below the seafloor. Here we used tag pyrosequencing of the V6 region of the 16S rRNA and full-length 16S rRNA sequencing on inactive hydrothermal sulfide chimney samples from 9°N on the East Pacific Rise to learn their bacterial composition, metabolic potential, and succession from venting to nonventing (inactive) regimes. Alpha-, beta-, delta-, and gammaproteobacteria and members of the phylum Bacteroidetes dominate all inactive sulfides. Greater than 26% of the V6 tags obtained are closely related to lineages involved in sulfur, nitrogen, iron, and methane cycling. Epsilonproteobacteria represent <4% of the V6 tags recovered from inactive sulfides and 15% of the full-length clones, despite their high abundance in active chimneys. Members of the phylum Aquificae, which are common in active vents, were absent from both the V6 tags and full-length 16S rRNA data sets. In both analyses, the proportions of alphaproteobacteria, betaproteobacteria, and members of the phylum Bacteroidetes were greater than those found on active hydrothermal sulfides. These shifts in bacterial population structure on inactive chimneys reveal ecological succession following cessation of venting and also imply a potential shift in microbial activity and metabolic guilds on hydrothermal sulfides, the dominant biome that results from seafloor venting. PMID:22275502

  9. Metabolic profiles using (1)H-nuclear magnetic resonance spectroscopy in postpartum dairy cows with ovarian inactivity.

    PubMed

    Xu, Chuchu; Xia, Cheng; Sun, Yuhang; Xiao, Xinhuan; Wang, Gang; Fan, Ziling; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Yang, Wei

    2016-10-01

    To understand the differences in metabolic changes between cows with ovarian inactivity and estrus cows, we selected cows at 60-90 days postpartum from an intensive dairy farm. According to clinical manifestations, B-ultrasound scan, rectal examination, 10 cows were assigned to the estrus group (A) and 10 to the ovarian inactivity group (B). All plasma samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy to compare plasma metabolomic profiles between the groups. We used multivariate pattern recognition to screen for different metabolites in plasma of anestrus cows. Compared with normal estrous cows, there were abnormalities in 12 kinds of metabolites in postpartum cows with ovarian inactivity (|r|> 0.602), including an increase in acetic acid (r = -0.817), citric acid (r = -0.767), and tyrosine (r = -0.714), and a decrease in low-density lipoprotein (r = 0.820), very low-density lipoprotein (r = 0.828), lipids (r = 0.769), alanine (r = 0.816), pyruvate (r = 0.721), creatine (r = 0.801), choline (r = 0.639), phosphorylcholine (r = 0.741), and glycerophosphorylcholine (r = 0.881). These metabolites were closely related to abnormality of glucose, amino acid, lipoprotein and choline metabolism, which may disturb the normal estrus. The decrease in plasma creatine and the increase in tyrosine were new changes for ovarian inactivity of postpartum cows. The decrease in plasma creatine and choline and the increase in tyrosine and p-hydroxyphenylalanine in cows with ovarian inactivity provide new directions for research on the mechanism of ovarian inactivity in cows. PMID:27291083

  10. Structure-Informed Design of an Enzymatically Inactive Vaccine Component for Group A Streptococcus

    PubMed Central

    Henningham, Anna; Ericsson, Daniel J.; Langer, Karla; Casey, Lachlan W.; Jovcevski, Blagojce; Chhatwal, G. Singh; Aquilina, J. Andrew; Batzloff, Michael R.; Kobe, Bostjan; Walker, Mark J.

    2013-01-01

    ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) causes ~700 million human infections/year, resulting in >500,000 deaths. There is no commercial GAS vaccine available. The GAS surface protein arginine deiminase (ADI) protects mice against a lethal challenge. ADI is an enzyme that converts arginine to citrulline and ammonia. Administration of a GAS vaccine preparation containing wild-type ADI, a protein with inherent enzymatic activity, may present a safety risk. In an approach intended to maximize the vaccine safety of GAS ADI, X-ray crystallography and structural immunogenic epitope mapping were used to inform vaccine design. This study aimed to knock out ADI enzyme activity without disrupting the three-dimensional structure or the recognition of immunogenic epitopes. We determined the crystal structure of ADI at 2.5 Å resolution and used it to select a number of amino acid residues for mutagenesis to alanine (D166, E220, H275, D277, and C401). Each mutant protein displayed abrogated activity, and three of the mutant proteins (those with the D166A, H275A, and D277A mutations) possessed a secondary structure and oligomerization state equivalent to those of the wild type, produced high-titer antisera, and avoided disruption of B-cell epitopes of ADI. In addition, antisera raised against the D166A and D277A mutant proteins bound to the GAS cell surface. The inactivated D166A and D277A mutant ADIs are ideal for inclusion in a GAS vaccine preparation. There is no human ortholog of ADI, and we confirm that despite limited structural similarity in the active-site region to human peptidyl ADI 4 (PAD4), ADI does not functionally mimic PAD4 and antiserum raised against GAS ADI does not recognize human PAD4. PMID:23919999

  11. Conversed mutagenesis of an inactive peptide to ASIC3 inhibitor for active sites determination.

    PubMed

    Osmakov, Dmitry I; Koshelev, Sergey G; Andreev, Yaroslav A; Dyachenko, Igor A; Bondarenko, Dmitry A; Murashev, Arkadii N; Grishin, Eugene V; Kozlov, Sergey A

    2016-06-15

    Peptide Ugr9-1 from the venom of sea anemone Urticina grebelnyi selectively inhibits the ASIC3 channel and significantly reverses inflammatory and acid-induced pain in vivo. A close homolog peptide Ugr 9-2 does not have these features. To find the pharmacophore residues and explore structure-activity relationships of Ugr 9-1, we performed site-directed mutagenesis of Ugr 9-2 and replaced several positions by the corresponding residues from Ugr 9-1. Mutant peptides Ugr 9-2 T9F and Ugr 9-2 Y12H were able to inhibit currents of the ASIC3 channels 2.2 times and 1.3 times weaker than Ugr 9-1, respectively. Detailed analysis of the spatial models of Ugr 9-1, Ugr 9-2 and both mutant peptides revealed the presence of the basic-aromatic clusters on opposite sides of the molecule, each of which is responsible for the activity. Additionally, Ugr9-1 mutant with truncated N- and C-termini retained similar with the Ugr9-1 action in vitro and was equally potent in vivo model of thermal hypersensitivity. All together, these results are important for studying the structure-activity relationships of ligand-receptor interaction and for the future development of peptide drugs from animal toxins. PMID:26686983

  12. Mutant p53: One, No One, and One Hundred Thousand

    PubMed Central

    Walerych, Dawid; Lisek, Kamil; Del Sal, Giannino

    2015-01-01

    Encoded by the mutated variants of the TP53 tumor suppressor gene, mutant p53 proteins are getting an increased experimental support as active oncoproteins promoting tumor growth and metastasis. p53 missense mutant proteins are losing their wild-type tumor suppressor activity and acquire oncogenic potential, possessing diverse transforming abilities in cell and mouse models. Whether various mutant p53s differ in their oncogenic potential has been a matter of debate. Recent discoveries are starting to uncover the existence of mutant p53 downstream programs that are common to different mutant p53 variants. In this review, we discuss a number of studies on mutant p53, underlining the advantages and disadvantages of alternative experimental approaches that have been used to describe the numerous mutant p53 gain-of-function activities. Therapeutic possibilities are also discussed, taking into account targeting either individual or multiple mutant p53 proteins in human cancer. PMID:26734571

  13. Intact Interval Timing in Circadian CLOCK Mutants

    PubMed Central

    Cordes, Sara; Gallistel, C. R.

    2008-01-01

    While progress has been made in determining the molecular basis for the circadian clock, the mechanism by which mammalian brains time intervals measured in seconds to minutes remains a mystery. An obvious question is whether the interval timing mechanism shares molecular machinery with the circadian timing mechanism. In the current study, we trained circadian CLOCK +/− and −/− mutant male mice in a peak-interval procedure with 10 and 20-s criteria. The mutant mice were more active than their wild-type littermates, but there were no reliable deficits in the accuracy or precision of their timing as compared with wild-type littermates. This suggests that expression of the CLOCK protein is not necessary for normal interval timing. PMID:18602902

  14. Oxygen sensitivity of an Escherichia coli mutant.

    PubMed

    Adler, H; Mural, R; Suttle, B

    1992-04-01

    Genetic evidence indicates that Oxys-6, an oxygen-sensitive mutant of Escherichia coli AB1157, is defective in the region of the hemB locus. Oxys-6 is capable of growth under aerobic conditions only if cultures are initiated at low-inoculum levels. Aerobic liquid cultures are limited to a cell density of 10(7) cells per ml by the accumulation of a metabolically produced, low-molecular-weight, heat-stable material in complex organic media. Both Oxys-6 and AB1157 cells produce the material, but only aerobic cultures of the mutant are inhibited by it. The material is produced by both intact cells and cell extracts in complex media. This reaction also occurs when the amino acid L-lysine is substituted for complex media. PMID:1551829

  15. Oxygen sensitivity of an Escherichia coli mutant.

    PubMed Central

    Adler, H; Mural, R; Suttle, B

    1992-01-01

    Genetic evidence indicates that Oxys-6, an oxygen-sensitive mutant of Escherichia coli AB1157, is defective in the region of the hemB locus. Oxys-6 is capable of growth under aerobic conditions only if cultures are initiated at low-inoculum levels. Aerobic liquid cultures are limited to a cell density of 10(7) cells per ml by the accumulation of a metabolically produced, low-molecular-weight, heat-stable material in complex organic media. Both Oxys-6 and AB1157 cells produce the material, but only aerobic cultures of the mutant are inhibited by it. The material is produced by both intact cells and cell extracts in complex media. This reaction also occurs when the amino acid L-lysine is substituted for complex media. Images PMID:1551829

  16. Recombination-deficient mutant of Streptococcus faecalis

    SciTech Connect

    Yagi, Y.; Clewell, D.B.

    1980-08-01

    An ultraviolet radiation-sensitive derivative of Streptococcus faecalis strain JH2-2 was isolated and found to be deficient in recombination, using a plasmid-plasmid recombination system. The strain was sensitive to chemical agents which interact with deoxyribonucleic acid and also underwent deoxyribonucleic acid degradation after ultraviolet irradiation. Thus, the mutant has properties similar to those of recA strains of Escherichia coli.

  17. Phospholipase C-related catalytically inactive protein (PRIP) regulates lipolysis in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase.

    PubMed

    Okumura, Toshiya; Harada, Kae; Oue, Kana; Zhang, Jun; Asano, Satoshi; Hayashiuchi, Masaki; Mizokami, Akiko; Tanaka, Hiroto; Irifune, Masahiro; Kamata, Nobuyuki; Hirata, Masato; Kanematsu, Takashi

    2014-01-01

    Phosphorylation of hormone-sensitive lipase (HSL) and perilipin by protein kinase A (PKA) promotes the hydrolysis of lipids in adipocytes. Although activation of lipolysis by PKA has been well studied, inactivation via protein phosphatases is poorly understood. Here, we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a binding partner for protein phosphatase 1 and protein phosphatase 2A (PP2A), is involved in lipolysis by regulating phosphatase activity. PRIP knockout (PRIP-KO) mice displayed reduced body-fat mass as compared with wild-type mice fed with standard chow ad libitum. Most other organs appeared normal, suggesting that mutant mice had aberrant fat metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated compared to that in wild-type mice. Starvation of wild-type mice or stimulation of adipose tissue explants with the catabolic hormone, adrenaline, translocated both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes was significantly reduced and was independent of adrenaline stimulation. Lipolysis activity, as assessed by measurement of non-esterified fatty acids and glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were treated with a phosphatase inhibitor, they showed a high lipolysis activity at the similar level to PRIP-KO adipocytes. Collectively, these results suggest that PRIP promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis. PMID:24945349

  18. Induced Dwarf Mutant in Catharanthus roseus with Enhanced Antibacterial Activity

    PubMed Central

    Verma, A. K.; Singh, R. R.

    2010-01-01

    Evaluation of an ethyl methane sulphonate-induced dwarf mutant of Catharanthus roseus (L.) G. Don revealed that the mutant exhibited marked variation in morphometric parameters. The in vitro antibacterial activity of the aqueous and alcoholic leaf extracts of the mutant and control plants was investigated against medically important bacteria. The mutant leaf extracts showed enhanced antibacterial activity against all the tested bacteria except Bacillus subtilis. PMID:21695004

  19. Sleep restores behavioral plasticity to Drosophila mutants

    PubMed Central

    Dissel, Stephane; Angadi, Veena; Kirszenblat, Leonie; Suzuki, Yasuko; Donlea, Jeff; Klose, Markus; Koch, Zachary; English, Denis; Winsky-Sommerer, Raphaelle; van Swinderen, Bruno; Shaw, Paul J.

    2015-01-01

    SUMMARY Given the role that sleep plays in modulating plasticity, we hypothesized that increasing sleep would restore memory to canonical memory mutants without specifically rescuing the causal molecular-lesion. Sleep was increased using three independent strategies: activating the dorsal Fan Shaped Body (FB), increasing the expression of Fatty acid binding protein (dFabp) or by administering the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP). Short-term memory (STM) or Long-term memory (LTM) was evaluated in rutabaga (rut) and dunce (dnc) mutants using Aversive Phototaxic Suppression (APS) and courtship conditioning. Each of the three independent strategies increased sleep and restored memory to rut and dnc mutants. Importantly, inducing sleep also reverses memory defects in a Drosophila model of Alzheimer’s disease. Together these data demonstrate that sleep plays a more fundamental role in modulating behavioral plasticity than previously appreciated and suggests that increasing sleep may benefit patients with certain neurological disorders. PMID:25913403

  20. Mutant Sodium Channel for Tumor Therapy

    PubMed Central

    Tannous, Bakhos A; Christensen, Adam P; Pike, Lisa; Wurdinger, Thomas; Perry, Katherine F; Saydam, Okay; Jacobs, Andreas H; García-Añoveros, Jaime; Weissleder, Ralph; Sena-Esteves, Miguel; Corey, David P; Breakefield, Xandra O

    2009-01-01

    Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein–Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant. PMID:19259066

  1. Induction of sarcomas by mutant IDH2

    PubMed Central

    Lu, Chao; Venneti, Sriram; Akalin, Altuna; Fang, Fang; Ward, Patrick S.; DeMatteo, Raymond G.; Intlekofer, Andrew M.; Chen, Chong; Ye, Jiangbin; Hameed, Meera; Nafa, Khedoudja; Agaram, Narasimhan P.; Cross, Justin R.; Khanin, Raya; Mason, Christopher E.; Healey, John H.; Lowe, Scott W.; Schwartz, Gary K.; Melnick, Ari; Thompson, Craig B.

    2013-01-01

    More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions. Regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification. In murine 10T1/2 mesenchymal progenitor cells, expression of mutant IDH2 led to DNA hypermethylation and an impairment in differentiation that could be reversed by treatment with DNA-hypomethylating agents. Introduction of mutant IDH2 also induced loss of contact inhibition and generated undifferentiated sarcomas in vivo. The oncogenic potential of mutant IDH2 correlated with the ability to produce 2-hydroxyglutarate. Together, these data demonstrate that neomorphic IDH2 mutations can be oncogenic in mesenchymal cells. PMID:24065766

  2. Registration of two allelic erect leaf mutants of sorghum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two allelic sorghum [Sorghum bicolor (L.) Moench] erect leaf (erl) mutants were isolated from an Annotated Individually-pedigreed Mutagenized Sorghum (AIMS) mutant library developed at the Plant Stress and Germplasm Development Unit, at Lubbock, Texas. The two mutants, erl1-1 and erl1-2, were isol...

  3. Targeting Oncogenic Mutant p53 for Cancer Therapy

    PubMed Central

    Parrales, Alejandro; Iwakuma, Tomoo

    2015-01-01

    Among genetic alterations in human cancers, mutations in the tumor suppressor p53 gene are the most common, occurring in over 50% of human cancers. The majority of p53 mutations are missense mutations and result in the accumulation of dysfunctional p53 protein in tumors. These mutants frequently have oncogenic gain-of-function activities and exacerbate malignant properties of cancer cells, such as metastasis and drug resistance. Increasing evidence reveals that stabilization of mutant p53 in tumors is crucial for its oncogenic activities, while depletion of mutant p53 attenuates malignant properties of cancer cells. Thus, mutant p53 is an attractive druggable target for cancer therapy. Different approaches have been taken to develop small-molecule compounds that specifically target mutant p53. These include compounds that restore wild-type conformation and transcriptional activity of mutant p53, induce depletion of mutant p53, inhibit downstream pathways of oncogenic mutant p53, and induce synthetic lethality to mutant p53. In this review article, we comprehensively discuss the current strategies targeting oncogenic mutant p53 in cancers, with special focus on compounds that restore wild-type p53 transcriptional activity of mutant p53 and those reducing mutant p53 levels. PMID:26732534

  4. 38 CFR 4.88c - Ratings for inactive nonpulmonary tuberculosis initially entitled after August 19, 1968.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Ratings for inactive nonpulmonary tuberculosis initially entitled after August 19, 1968. 4.88c Section 4.88c Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings Infectious Diseases, Immune Disorders...

  5. Physical Inactivity in U.S. Adolescents: Family, Neighborhood, and Individual Factors. Research Brief. Publication #2009-28

    ERIC Educational Resources Information Center

    Terzian, Mary; Moore, Kristin Anderson

    2009-01-01

    Concern about physical inactivity among U.S. youth has been mounting in recent years, in light of studies suggesting that few adolescents (about one out of three) engage in recommended levels of physical activity. Although much attention has been paid to individual factors that may contribute to this problem, such as television viewing and…

  6. Inactivity-induced respiratory plasticity: protecting the drive to breathe in disorders that reduce respiratory neural activity.

    PubMed

    Strey, K A; Baertsch, N A; Baker-Herman, T L

    2013-11-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

  7. Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

    PubMed Central

    Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

    2013-01-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

  8. Taking Part Counts: Adolescents' Experiences of the Transition from Inactivity to Active Participation in School-Based Physical Education

    ERIC Educational Resources Information Center

    Brooks, Fiona; Magnusson, Josefine

    2006-01-01

    Identifying ways to increase and sustain active living among young people represents a priority for health promotion interventions. This qualitative study explored the experiences of adolescent boys and girls in the United Kingdom (aged 14-15 years) who had made the transition from inactivity to active participation in physical education (PE). The…

  9. Bacterial and archaeal communities in the deep-sea sediments of inactive hydrothermal vents in the Southwest India Ridge

    PubMed Central

    Zhang, Likui; Kang, Manyu; Xu, Jiajun; Xu, Jian; Shuai, Yinjie; Zhou, Xiaojian; Yang, Zhihui; Ma, Kesen

    2016-01-01

    Active deep-sea hydrothermal vents harbor abundant thermophilic and hyperthermophilic microorganisms. However, microbial communities in inactive hydrothermal vents have not been well documented. Here, we investigated bacterial and archaeal communities in the two deep-sea sediments (named as TVG4 and TVG11) collected from inactive hydrothermal vents in the Southwest India Ridge using the high-throughput sequencing technology of Illumina MiSeq2500 platform. Based on the V4 region of 16S rRNA gene, sequence analysis showed that bacterial communities in the two samples were dominated by Proteobacteria, followed by Bacteroidetes, Actinobacteria and Firmicutes. Furthermore, archaeal communities in the two samples were dominated by Thaumarchaeota and Euryarchaeota. Comparative analysis showed that (i) TVG4 displayed the higher bacterial richness and lower archaeal richness than TVG11; (ii) the two samples had more divergence in archaeal communities than bacterial communities. Bacteria and archaea that are potentially associated with nitrogen, sulfur metal and methane cycling were detected in the two samples. Overall, we first provided a comparative picture of bacterial and archaeal communities and revealed their potentially ecological roles in the deep-sea environments of inactive hydrothermal vents in the Southwest Indian Ridge, augmenting microbial communities in inactive hydrothermal vents. PMID:27169490

  10. Microplate-based active/inactive 1 screen for biomass degrading enzyme library purification and gene discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present here a whole-cell and permeabilized E. coli cell 1' active/inactive microplate screen for ß-D-xylosidase, xylanase, endocellulase, and ferulic acid esterase enzyme activities which are critical for the enzymatic deconstruction of biomass for fuels and chemicals. Transformants from genomic...

  11. Gene expression in human lupus: bone marrow differentiates active from inactive patients and displays apoptosis and granulopoiesis signatures

    PubMed Central

    Nakou, Magdalene; Knowlton, Nicholas; Frank, Mark B.; Bertsias, George; Osban, Jeanette; Sandel, Clayton E.; Papadaki, Eleni; Raptopoulou, Amalia; Sidiropoulos, Prodromos; Kritikos, Heraklis; Tassiulas, Ioannis; Centola, Michael; Boumpas, Dimitrios T.

    2009-01-01

    Objective The cells of the immune system originate from the bone marrow (BM), where many of them also mature. To better understand the aberrant immune response in systemic lupus erythematosus (SLE), we examined the BM in lupus patients using DNA microarrays and compared it to the peripheral blood (PB). Patients and Methods Bone marrow mononuclear cells (BMMCs) from 20 SLE patients (11 with active disease and 9 with inactive disease) and peripheral blood mononuclear cells (PBMCs) from 27 patients (16 active/ 11 inactive); BMMCs and PBMCs from 7 healthy individuals and 3 osteoarthritis patients served as controls. Samples were analyzed on genome-scale microarrays with 21,329 genes represented. Results We found 102 differentially expressed genes between patients’ and controls’ BMMCs (unpaired student t-test), involved in various biologic processes; 53 of them are involved in major networks including cell death, growth, signaling and proliferation. Comparative analysis between BM and PB of patients identified 88 genes differentially expressed; 61 out of 88 participate in cell growth and differentiation, cellular movement and morphology, immune response and other hematopoietic cell functions. Unsupervised clustering of highly expressed genes revealed two major SLE patient clusters (active and inactive) in BM, but not in PB. The upregulated genes in the bone marrow of active patients included genes involved in cell death and granulopoiesis. Conclusion Microarray analysis of the bone marrow differentiates active from inactive lupus patients and provides further evidence for the role of apoptosis and granulocytes in the pathogenesis of the disease. PMID:18975309

  12. Correlates of the Intention to Remain Sexually Inactive among Underserved Hispanic and African American High School Students

    ERIC Educational Resources Information Center

    Bazargan, Mohsen; West, Kimberly

    2006-01-01

    The objective of this study was to apply the Information-Motivation-Behavior (IMB) theoretical framework to examine the correlates of the intention to remain sexually inactive among Hispanic and African American high school students. This study utilized a cross-sectional survey of high school students. The setting was the unified school districts…

  13. 37 CFR 11.58 - Duties of disciplined or resigned practitioner, or practitioner on disability inactive status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Duties of disciplined or resigned practitioner, or practitioner on disability inactive status. 11.58 Section 11.58 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE REPRESENTATION OF OTHERS BEFORE THE UNITED STATES PATENT...

  14. Determining the Rotation Periods of an Inactive LEO Satellite and the First Korean Space Debris on GEO, KOREASAT 1

    NASA Astrophysics Data System (ADS)

    Choi, Jin; Jo, Jung Hyun; Kim, Myung-Jin; Roh, Dong-Goo; Park, Sun-Youp; Lee, Hee-Jae; Park, Maru; Choi, Young-Jun; Yim, Hong-Suh; Bae, Young-Ho; Park, Young-Sik; Cho, Sungki; Moon, Hong-Kyu; Choi, Eun-Jung; Jang, Hyun-Jung; Park, Jang-Hyun

    2016-06-01

    Inactive space objects are usually rotating and tumbling as a result of internal or external forces. KOREASAT 1 has been inactive since 2005, and its drift trajectory has been monitored with the optical wide-field patrol network (OWL-Net). However, a quantitative analysis of KOREASAT 1 in regard to the attitude evolution has never been performed. Here, two optical tracking systems were used to acquire raw measurements to analyze the rotation period of two inactive satellites. During the optical campaign in 2013, KOREASAT 1 was observed by a 0.6 m class optical telescope operated by the Korea Astronomy and Space Science Institute (KASI). The rotation period of KOREASAT 1 was analyzed with the light curves from the photometry results. The rotation periods of the low Earth orbit (LEO) satellite ASTRO-H after break-up were detected by OWL-Net on April 7, 2016. We analyzed the magnitude variation of each satellite by differential photometry and made comparisons with the star catalog. The illumination effect caused by the phase angle between the Sun and the target satellite was corrected with the system tool kit (STK) and two line element (TLE) technique. Finally, we determined the rotation period of two inactive satellites on LEO and geostationary Earth orbit (GEO) with light curves from the photometry. The main rotation periods were determined to be 5.2 sec for ASTRO-H and 74 sec for KOREASAT 1.

  15. Bacterial and archaeal communities in the deep-sea sediments of inactive hydrothermal vents in the Southwest India Ridge

    NASA Astrophysics Data System (ADS)

    Zhang, Likui; Kang, Manyu; Xu, Jiajun; Xu, Jian; Shuai, Yinjie; Zhou, Xiaojian; Yang, Zhihui; Ma, Kesen

    2016-05-01

    Active deep-sea hydrothermal vents harbor abundant thermophilic and hyperthermophilic microorganisms. However, microbial communities in inactive hydrothermal vents have not been well documented. Here, we investigated bacterial and archaeal communities in the two deep-sea sediments (named as TVG4 and TVG11) collected from inactive hydrothermal vents in the Southwest India Ridge using the high-throughput sequencing technology of Illumina MiSeq2500 platform. Based on the V4 region of 16S rRNA gene, sequence analysis showed that bacterial communities in the two samples were dominated by Proteobacteria, followed by Bacteroidetes, Actinobacteria and Firmicutes. Furthermore, archaeal communities in the two samples were dominated by Thaumarchaeota and Euryarchaeota. Comparative analysis showed that (i) TVG4 displayed the higher bacterial richness and lower archaeal richness than TVG11; (ii) the two samples had more divergence in archaeal communities than bacterial communities. Bacteria and archaea that are potentially associated with nitrogen, sulfur metal and methane cycling were detected in the two samples. Overall, we first provided a comparative picture of bacterial and archaeal communities and revealed their potentially ecological roles in the deep-sea environments of inactive hydrothermal vents in the Southwest Indian Ridge, augmenting microbial communities in inactive hydrothermal vents.

  16. Bacterial and archaeal communities in the deep-sea sediments of inactive hydrothermal vents in the Southwest India Ridge.

    PubMed

    Zhang, Likui; Kang, Manyu; Xu, Jiajun; Xu, Jian; Shuai, Yinjie; Zhou, Xiaojian; Yang, Zhihui; Ma, Kesen

    2016-01-01

    Active deep-sea hydrothermal vents harbor abundant thermophilic and hyperthermophilic microorganisms. However, microbial communities in inactive hydrothermal vents have not been well documented. Here, we investigated bacterial and archaeal communities in the two deep-sea sediments (named as TVG4 and TVG11) collected from inactive hydrothermal vents in the Southwest India Ridge using the high-throughput sequencing technology of Illumina MiSeq2500 platform. Based on the V4 region of 16S rRNA gene, sequence analysis showed that bacterial communities in the two samples were dominated by Proteobacteria, followed by Bacteroidetes, Actinobacteria and Firmicutes. Furthermore, archaeal communities in the two samples were dominated by Thaumarchaeota and Euryarchaeota. Comparative analysis showed that (i) TVG4 displayed the higher bacterial richness and lower archaeal richness than TVG11; (ii) the two samples had more divergence in archaeal communities than bacterial communities. Bacteria and archaea that are potentially associated with nitrogen, sulfur metal and methane cycling were detected in the two samples. Overall, we first provided a comparative picture of bacterial and archaeal communities and revealed their potentially ecological roles in the deep-sea environments of inactive hydrothermal vents in the Southwest Indian Ridge, augmenting microbial communities in inactive hydrothermal vents. PMID:27169490

  17. Self-reported physical inactivity and health complaints: a cross-sectional study of Lithuanian adolescent schoolgirls.

    PubMed

    Malinauskas, Romualdas; Malinauskaiene, Vilija

    2015-05-01

    The study aimed to investigate the associations between physical inactivity and health complaints in relation to posttraumatic stress (PTS) symptoms, behavioral and nutritional factors, and sense of coherence (SOC) in eighth-grade girls enrolled in secondary schools in Kaunas, Lithuania. A random sample of girls (N = 862) was interviewed anonymously on health complaints, physical activity level, PTS symptoms, Antonovsky's SOC scale, health behaviors, and dietary patterns. All health complaints were significantly associated with physical inactivity. Crude odds ratio (OR) for physical inactivity and health complaints was 1.67 (95%CI: 1.09-2.56); after adjusting for PTS symptoms, the OR decreased to 1.57 (95%CI: 0.95-2.45); further adjustment for smoking, daily alcohol intake, daily consumption of fresh vegetables, and SOC decreased the OR to 1.25 (95%CI: 0.76-2.04). The effect of PTS symptoms and sense of coherence remained stable after all adjustments. The significant association between physical inactivity and health complaints was mediated by PTS symptoms. PMID:26083173

  18. Youth at risk of physical inactivity may benefit more from activity-related support than youth not at risk

    PubMed Central

    Davison, Kirsten Krahnstoever; Schmalz, Dorothy L

    2006-01-01

    Background This study examines whether associations between activity-related support and adolescents' physical activity differ for adolescents at high versus low risk of physical inactivity. Methods: Participants included 202 middle-school-aged girls (N = 92) and boys (N = 110). Physical activity was assessed using three self-report questionnaires. Activity-related support from mothers, fathers, siblings, and peers was assessed using the Activity Support Scale. Perceived sport competence was assessed using the Physical Activity Self Description Questionnaire. Participants' height and weight were measured and used to calculate their age- and sex-adjusted Body Mass Index percentile. Participants were classified as being at high risk for physical inactivity if they fulfilled two of the following three criteria: (1) overweight; (2) female; or (3) having low perceived sport competence. Results: Activity-related support from all sources was associated with higher levels of physical activity among adolescents. A stronger association between activity support and physical activity was found for adolescents at high risk for physical inactivity in comparison to adolescents at low risk. Conclusions: Findings from this study suggest that the activity-related support from family and friends may be an effective tool in promoting physical activity among youth at risk of physical inactivity. PMID:16566842

  19. The Designing and Development of a Program to Prepare Inactive Registered Nurses for Reentry into Practice. Curriculum Development.

    ERIC Educational Resources Information Center

    Belock, Shirley

    The planning and design of a course for the inactive registered nurse desiring to return to active practice is reported in this practicum paper. Current literature was reviewed with emphasis on the needs in rural states, such as Vermont, and characteristics of the target group. The first three modules of the course were developed, entitled: The…

  20. Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated

    PubMed Central

    Almeida, Beverley; Campanilho‐Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A.; Wedderburn, Lucy R.; Armon, Kate; Briggs, Vanja; Ellis‐Gage, Joe; Roper, Holly; Watts, Joanna; Baildam, Eileen; Hanna, Louise; Lloyd, Olivia; McCann, Liza; Roberts, Ian; McGovern, Ann; Riley, Phil; Al‐Abadi, Eslam; Ryder, Clive; Scott, Janis; Southwood, Taunton; Thomas, Beverley; Amin, Tania; Burton, Deborah; Jackson, Gillian; Van Rooyen, Vanessa; Wood, Mark; Wyatt, Sue; Browne, Michael; Davidson, Joyce; Ferguson, Sue; Gardner‐Medwin, Janet; Martin, Neil; Waxman, Liz; Foster, Helen; Friswell, Mark; Jandial, Sharmila; Qiao, Lisa; Sen, Ethan; Smith, Eve; Stevenson, Vicky; Swift, Alison; Wade, Debbie; Watson, Stuart; Crate, Lindsay; Frost, Anna; Jordan, Mary; Mosley, Ellen; Satyapal, Rangaraj; Stretton, Elizabeth; Venning, Helen; Warrier, Kishore; Almeida, Beverley; Arnold, Katie; Beard, Laura; Brown, Virginia; Campanilho‐Marques, Raquel; Enayat, Elli; Glackin, Yvonne; Halkon, Elizabeth; Hasson, Nathan; Juggins, Audrey; Kassoumeri, Laura; Lunt, Sian; Maillard, Sue; Nistala, Kiran; Pilkington, Clarissa; Simou, Stephanie; Smith, Sally; Varsani, Hemlata; Wedderburn, Lucy; Murray, Kevin; Ioannou, John; Suffield, Linda; Al‐Obaidi, Muthana; Leach, Sam; Lee, Helen; Smith, Helen; Inness, Emma; Kendall, Eunice; Mayers, David; Wilkinson, Nick; Clinch, Jacqui; Pluess‐Hall, Helen

    2015-01-01

    Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met

  1. Maternal inflammation during late pregnancy is lower in physically active compared to inactive obese women

    PubMed Central

    Tinius, Rachel A.; Cahill, Alison G.; Strand, Eric A.; Todd Cade, W.

    2016-01-01

    Purpose The primary purpose of this study was to compare maternal plasma inflammation between physically active and inactive obese women during late pregnancy. The secondary purpose was to examine the relationships between maternal plasma inflammation and lipid metabolism and maternal and neonatal metabolic health in these women. Methods A cross-sectional, observational study design was performed in 16 obese-inactive ((OBI) age: 25.0 ± 4.8 years, pre-pregnancy BMI: 36.3 ± 4.3kg/m2, body fat percentage in late gestation: 37.7 ± 3.5%) and 16 obese-active ((OBA) age: 28.9 ± 4.8 years, pre-pregnancy BMI: 34.0±3.7kg/m2, body fat in late gestation: 36.6 ± 3.8%) women during the third trimester of pregnancy. Maternal plasma inflammation (C -reactive protein (CRP)) and insulin resistance (Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) were measured at rest. Plasma lipid concentration and metabolism (lipid oxidation and lipolysis) were measured at rest, during a 30-minute bout of low-intensity (40% VO2peak) exercise, and during a resting recovery period using indirect calorimetry. Umbilical cord blood was collected for measurement of neonatal plasma insulin resistance, inflammation, and lipid concentration. Neonatal body composition was measured via air displacement plethysmography. Results Maternal plasma CRP concentration was significantly higher in OBI compared to OBA women (9.1 ± 4.0 mg/L versus 6.3 ±2.5mg/L, p=0.02). Maternal plasma CRP concentration was significantly associated with maternal lipolysis (r=0.43, p=0.02), baseline lipid oxidation rate (r=0.39, p=0.03), and baseline plasma free fatty acid concentration (r=0.36, p=0.04). Conclusions Maternal physical activity may reduce inflammation during pregnancy in obese women. Maternal lipid metabolism is related to systemic inflammation. PMID:26799789

  2. Aerobics, Quality of Life, and Physiological Indicators of Inactive Male Students’ Cardiovascular Endurances, in Kashan

    PubMed Central

    Bahram, Mohammad Ebrahim; Akkasheh, Gudarz; Akkasheh, Negar

    2014-01-01

    Background: Studies show that lack of exercise and physical activity during childhood and teenage years is directly related to different diseases in adulthood. Objectives: The main purpose of this study was to investigate the effects of an eight-week aerobic exercise on the quality of life as well as physiological indicators of cardiovascular endurance of inactive high school male students in Kashan. Materials and Methods: The study was a field trial using pretest and post-test. Three hundred high school male students in Kashan, Iran, were recruited and interviewed by the researchers, using a questionnaire. Of the inactive ones, 30 who reached the highest criteria standards, were selected as samples and randomly divided to two equal groups. The maximum consumed oxygen (VO2max) and resting heart rate were measured by Quinn aerobic test, and the quality of life was measured by the World Health Organization Quality of Life (WHOQOL-26-Breef) questionnaire. The exercise program included an eight-week aerobic exercise, three times per week, with 60%-75% of the maximum heart beat. During the exercise, the subjects had no other sport activity. To check the normal distribution of the data, Kolmogorov-Smirnov test was used. To evaluate the pretest and post-test results, paired t-test was used and for comparing the groups, independent t-test was applied. All the analyses were performed by SPSS software version 16. Results: The mean ages of intervention and control groups were 17.46 ± 1.30 and 17.53 ± 1.18, respectively. The mean weight of the intervention group was 56.73 ± 9.91 kg and its mean body mass index (BMI) was 19.88 ± 3.42. In the control group, the mean weigh and BMI were 60.06 ± 11.96 kg and 20.79 ± 3.51, respectively. The quality of life and its components improved significantly in the intervention group (physical (P = 0.0001), mental (P = 0.0001), social (P = 0.0001), and environmental (P = 0.0001) aspects). VO2max (P = 0.001) and the resting heart beat (P

  3. Southern high latitude dune fields on Mars: Morphology, aeolian inactivity, and climate change

    USGS Publications Warehouse

    Fenton, L.K.; Hayward, R.K.

    2010-01-01

    In a study area spanning the martian surface poleward of 50?? S., 1190 dune fields have been identified, mapped, and categorized based on dune field morphology. Dune fields in the study area span ??? 116400km2, leading to a global dune field coverage estimate of ???904000km2, far less than that found on Earth. Based on distinct morphological features, the dune fields were grouped into six different classes that vary in interpreted aeolian activity level from potentially active to relatively inactive and eroding. The six dune field classes occur in specific latitude zones, with a sequence of reduced activity and degradation progressing poleward. In particular, the first signs of stabilization appear at ???60?? S., which broadly corresponds to the edge of high concentrations of water-equivalent hydrogen content (observed by the Neutron Spectrometer) that have been interpreted as ground ice. This near-surface ground ice likely acts to reduce sand availability in the present climate state on Mars, stabilizing high latitude dunes and allowing erosional processes to change their morphology. As a result, climatic changes in the content of near-surface ground ice are likely to influence the level of dune activity. Spatial variation of dune field classes with longitude is significant, suggesting that local conditions play a major role in determining dune field activity level. Dune fields on the south polar layered terrain, for example, appear either potentially active or inactive, indicating that at least two generations of dune building have occurred on this surface. Many dune fields show signs of degradation mixed with crisp-brinked dunes, also suggesting that more than one generation of dune building has occurred since they originally formed. Dune fields superposed on early and late Amazonian surfaces provide potential upper age limits of ???100My on the south polar layered deposits and ???3Ga elsewhere at high latitudes. No craters are present on any identifiable dune

  4. WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with Gα12/13.

    PubMed

    Arthofer, Elisa; Hot, Belma; Petersen, Julian; Strakova, Katerina; Jäger, Stefan; Grundmann, Manuel; Kostenis, Evi; Gutkind, J Silvio; Schulte, Gunnar

    2016-10-01

    Frizzleds (FZDs) are unconventional G protein-coupled receptors that belong to the class Frizzled. They are bound and activated by the Wingless/Int-1 lipoglycoprotein (WNT) family of secreted lipoglycoproteins. To date, mechanisms of signal initiation and FZD-G protein coupling remain poorly understood. Previously, we showed that FZD6 assembles with Gαi1/Gαq (but not with Gαs, Gαo and Ga12/13), and that these inactive-state complexes are dissociated by WNTs and regulated by the phosphoprotein Dishevelled (DVL). Here, we investigated the inactive-state assembly of heterotrimeric G proteins with FZD4, a receptor important in retinal vascular development and frequently mutated in Norrie disease or familial exudative vitreoretinopathy. Live-cell imaging experiments using fluorescence recovery after photobleaching show that human FZD4 assembles-in a DVL-independent manner-with Gα12/13 but not representatives of other heterotrimeric G protein subfamilies, such as Gαi1, Gαo, Gαs, and Gαq The FZD4-G protein complex dissociates upon stimulation with WNT-3A, WNT-5A, WNT-7A, and WNT-10B. In addition, WNT-induced dynamic mass redistribution changes in untransfected and, even more so, in FZD4 green fluorescent protein-transfected cells depend on Gα12/13 Furthermore, expression of FZD4 and Gα12 or Gα13 in human embryonic kidney 293 cells induces WNT-dependent membrane recruitment of p115-RHOGEF (RHO guanine nucleotide exchange factor, molecular weight 115 kDa), a direct target of Gα12/13 signaling, underlining the functionality of an FZD4-Gα12/13-RHO signaling axis. In summary, Gα12/13-mediated WNT/FZD4 signaling through p115-RHOGEF offers an intriguing and previously unappreciated mechanistic link of FZD4 signaling to cytoskeletal rearrangements and RHO signaling with implications for the regulation of angiogenesis during embryonic and tumor development. PMID:27458145

  5. Maternal inflammation during late pregnancy is lower in physically active compared with inactive obese women.

    PubMed

    Tinius, Rachel A; Cahill, Alison G; Strand, Eric A; Cade, W Todd

    2016-02-01

    The primary purpose of this study was to compare maternal plasma inflammation between physically active and inactive obese women during late pregnancy. The secondary purpose was to examine the relationships between maternal plasma inflammation and lipid metabolism and maternal and neonatal metabolic health in these women. A cross-sectional, observational study design was performed in 16 obese-inactive (OBI; means ± SD; age, 25.0 ± 4.8 years; prepregnancy body mass index (BMI), 36.3 ± 4.3 kg/m(2); body fat percentage in late gestation, 37.7% ± 3.5%) and 16 obese-active (OBA; age, 28.9 ± 4.8 years; prepregnancy BMI, 34.0 ± 3.7 kg/m(2); body fat in late gestation, 36.6% ± 3.8%) women during the third trimester of pregnancy. Maternal plasma inflammation (C -reactive protein (CRP)) and insulin resistance (Homeostatic Model Assessment-Insulin Resistance) were measured at rest. Plasma lipid concentration and metabolism (lipid oxidation and lipolysis) were measured at rest, during a 30-min bout of low-intensity (40% peak oxygen uptake) exercise, and during a resting recovery period using indirect calorimetry. Umbilical cord blood was collected for measurement of neonatal plasma insulin resistance, inflammation, and lipid concentration. Neonatal body composition was measured via air displacement plethysmography. Maternal plasma CRP concentration was significantly higher in OBI compared with OBA women (9.1 ± 4.0 mg/L vs. 6.3 ± 2.5 mg/L, p = 0.02). Maternal plasma CRP concentration was significantly associated with maternal lipolysis (r = 0.43, p = 0.02), baseline lipid oxidation rate (r = 0.39, p = 0.03), and baseline plasma free fatty acid concentration (r = 0.36, p = 0.04). In conclusion, maternal physical activity may reduce inflammation during pregnancy in obese women. Maternal lipid metabolism is related to systemic inflammation. PMID:26799789

  6. Radium-226 in vegetation and substrates at inactive uranium mill sites

    SciTech Connect

    Marple, M.L.

    1980-01-01

    Results of a study of the content of radium-226 in plants growing on inactive uranium mill tailings sites in the Four Corners Region of the southwestern United States and in plants grown under greenhouse conditions with minimal surficial contamination are reported. Field plant samples and associated substrates were analyzed from two carbonate tailings sites in the Grants Mineral Belt of New Mexico. Radium activities in air-cleaned samples ranged from 5 to 368 pCi/g (dry weight) depending on species and location: activities in plants growing on local soils averaged 1.0 pCi/g. The talings and local soils contain 140 to 1400 pCi/g and 2.1 pCi/g, respectively. An evaluation of cleaning methods on selected samples showed that from 17 to 79% of the radium activity measured in air-cleaned samples was due to surficial contamination, which varied with species and location. A survey of 18 inactive uranium mill sites in the Four Corners Region was performed. Radium activity in plant tissues from nine species ranged from 2 to 210 pCi/g on bare tailings and from 0.3 to 30 pCi/g on covered tailings The radium content in most of the soil overburdens on the covered tailings piles was 10 to 17 pCi/g. An experiment was performed to measure radium-226 uptake by two species grown on tailings covered with a shallow (5 cm) soil layer. A grass, Sporobolus airoides (alkali sacaton) and a shrub, Atriplex canescens (four-wing saltbush), were studied. The tailings were a mixture of sands and slimes from a carbonate pile. The tailings treatments were plants grown in a soil cover over tailings; the controls were plants grown only in soil. Three soil types, dune sand, clay loam, and loam, were used. The radium activity of the plant tissue from the tailings treatment compared to that of the appropriate control was 1 to 19 times greater for the grass and 4 to 27 times greater for the shrub.

  7. Dynamics of vitamin D in patients with mild or inactive inflammatory bowel disease and their families

    PubMed Central

    2013-01-01

    Background 25(OH) vitamin D levels may be low in patients with moderately or severely active inflammatory bowel diseases (IBD: Crohn’s disease and Idiopathic Ulcerative Colitis) but this is less clear in patients with mild or inactive IBD. Furthermore there is limited information of any family influence on 25(OH) vitamin D levels in IBD. As a possible risk factor we hypothesize that vitamin D levels may also be low in families of IBD patients. Objectives To evaluate 25[OH] vitamin D levels in patients with IBD in remission or with mild activity. A second objective is to evaluate whether there are relationships within IBD family units of 25[OH] vitamin D and what are the influences associated with these levels. Methods Participants underwent medical history, physical examination and a 114 item diet questionnaire. Serum 25[OH] vitamin D was measured, using a radioimmunoassay kit, (replete ≥ 75, insufficient 50–74, deficient < 25–50, or severely deficient < 25 nmol/L). Associations between 25[OH] vitamin D and twenty variables were evaluated using univariate regression. Multivariable analysis was also applied and intrafamilial dynamics were assessed. Results 55 patients and 48 controls with their respective families participated (N206). 25[OH] vitamin D levels between patients and controls were similar (71.2 ± 32.8 vs. 68.3 ±26.2 nmol/L). Vitamin D supplements significantly increased intake but correlation with serum 25[OH] vitamin D was significant only during non sunny months among patients. Within family units, patients’ families had mean replete levels (82.3 ± 34.2 nmol/L) and a modest correlation emerged during sunny months between patients and family (r2 =0.209 p = 0.032). These relationships were less robust and non significant in controls and their families. Conclusions In patients with mild or inactive IBD 25[OH] vitamin D levels are less than ideal but are similar to controls. Taken together collectively, the results

  8. Adolescent physical activity and inactivity: a prospective study of risk of benign breast disease in young women.

    PubMed

    Berkey, Catherine S; Tamimi, Rulla M; Willett, Walter C; Rosner, Bernard; Lindsay Frazier, A; Colditz, Graham A

    2014-08-01

    In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. The Growing Up Today Study includes 9,039 females, 9-15 years at study initiation (1996), who completed questionnaires annually through 2001, then in 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996-2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18 years) reported whether they had ever been diagnosed with BBD confirmed by breast biopsy (n = 133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR = 0.61, ≥30 vs ≤15 min/day; p = .049). We observed no evidence that inactivity (≥3 vs <2 h/day OR = 1.02, p = .92) or METS (top vs bottom tertile OR = 1.19, p = .42) were associated with BBD. Accounting for factors including family history, childhood adiposity, and other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed. PMID:25034340

  9. Adolescent Physical Activity and Inactivity: A Prospective Study of Risk of Benign Breast Disease in Young Women

    PubMed Central

    Berkey, Catherine S.; Tamimi, Rulla M.; Willett, Walter C.; Rosner, Bernard; Frazier, A. Lindsay; Colditz, Graham A.

    2016-01-01

    Purpose In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. Methods The Growing Up Today Study (GUTS) includes 9039 females, 9–15yrs at study initiation (1996), who completed questionnaires annually through 2001, then 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996–2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18yr) reported whether they had been diagnosed with BBD confirmed by breast biopsy (n=133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Results Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR=0.61,p=.049, ≥30min/day vs ≤15min/day). We observed no evidence that inactivity (≥3 hrs/day vs <2hr/day OR=1.02,p=.92) or METS (top vs bottom tertile OR=1.19,p=.42) were associated with BBD. Conclusion Accounting for factors including family history, childhood adiposity, other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed. PMID:25034340

  10. Loss of Catalytically Inactive Lipid Phosphatase Myotubularin-related Protein 12 Impairs Myotubularin Stability and Promotes Centronuclear Myopathy in Zebrafish

    PubMed Central

    Gupta, Vandana A.; Hnia, Karim; Smith, Laura L.; Gundry, Stacey R.; McIntire, Jessica E.; Shimazu, Junko; Bass, Jessica R.; Talbot, Ethan A.; Amoasii, Leonela; Goldman, Nathaniel E.; Laporte, Jocelyn; Beggs, Alan H.

    2013-01-01

    X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by mutations of the myotubularin gene, MTM1. Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., “MTMRs”). Biochemically, catalytically inactive MTMRs have been shown to form heteroligomers with active members within the myotubularin family through protein-protein interactions. However, the pathophysiological significance of catalytically inactive MTMRs remains unknown in muscle. By in vitro as well as in vivo studies, we have identified that catalytically inactive myotubularin-related protein 12 (MTMR12) binds to myotubularin in skeletal muscle. Knockdown of the mtmr12 gene in zebrafish resulted in skeletal muscle defects and impaired motor function. Analysis of mtmr12 morphant fish showed pathological changes with central nucleation, disorganized Triads, myofiber hypotrophy and whorled membrane structures similar to those seen in X-linked myotubular myopathy. Biochemical studies showed that deficiency of MTMR12 results in reduced levels of myotubularin protein in zebrafish and mammalian C2C12 cells. Loss of myotubularin also resulted in reduction of MTMR12 protein in C2C12 cells, mice and humans. Moreover, XLMTM mutations within the myotubularin interaction domain disrupted binding to MTMR12 in cell culture. Analysis of human XLMTM patient myotubes showed that mutations that disrupt the interaction between myotubularin and MTMR12 proteins result in reduction of both myotubularin and MTMR12. These studies strongly support the concept that interactions between myotubularin and MTMR12 are required for the stability of their functional protein complex in normal skeletal muscles. This work highlights an important physiological function of catalytically inactive phosphatases in the pathophysiology of myotubular myopathy and suggests a novel therapeutic approach through identification of

  11. Neighbourhood inequalities in physical inactivity: the role of neighbourhood attractiveness, proximity to local facilities and safety in the Netherlands.

    PubMed

    van Lenthe, F J; Brug, J; Mackenbach, J P

    2005-02-01

    We investigated the association between the neighbourhood socioeconomic environment and physical inactivity, and explored the contribution of neighbourhood characteristics to this association. Data were analysed of 20-69 years old participants of the Dutch GLOBE study who lived in 78 neighbourhoods of Eindhoven (n = 8.767). The neighbourhood socioeconomic environment was assessed from aggregated self-reported information of participants' education and occupation level, and employment status. Aspects of physical inactivity investigated were based on the time spent on (a) walking and cycling to shops or work, (b) walking, cycling and gardening in leisure time, and (c) participation in sports activities. Characteristics of neighbourhoods included the proximity to food shops, general physical design of neighbourhoods, quality of green facilities, noise pollution from traffic and required police attention as evaluated by municipal services (professionals) responsible for these characteristics. Compared to those living in the most advantaged neighbourhoods, residents living in the quartile of socio-economically most disadvantaged neighbourhoods were more likely to walk or cycle to shops or work, but less likely to walk, cycle or garden in leisure time and less likely to participate in sports activities (adjusted for age, sex and individual educational level). Neighbourhood inequalities in walking or cycling to shops or work were not mediated by specific neighbourhood characteristics included in our analyses. The increased probability of almost never walking, cycling and gardening in leisure time in the most disadvantaged neighbourhoods was partly mediated by a poorer general physical design in these neighbourhoods. Similarly, the increased probability of almost never participating in sports activities in the most disadvantaged neighbourhoods was partly mediated by larger amounts of required police attention. The direction of neighbourhood inequalities differs for aspects

  12. New therapeutic strategies for BRAF mutant colorectal cancers

    PubMed Central

    2015-01-01

    Oncogenic BRAF mutations are found in ~10% of colorectal cancers (CRCs) and predict poor prognosis. Although BRAF inhibitors have demonstrated striking efficacy in BRAF mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF mutant CRC. Over the past few years, studies have begun to define the molecular mechanisms underlying the relative resistance of BRAF mutant CRC to BRAF inhibitors, leading to the development of novel therapeutic strategies that are showing promising clinical activity in initial clinical trials. Our current understanding of the mechanisms of BRAF inhibitor resistance in BRAF mutant CRC and the therapeutic approaches currently in clinical trials for BRAF mutant CRC are reviewed herein. PMID:26697198

  13. Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles.

    PubMed

    Ikezoe, Tome; Mori, Natsuko; Nakamura, Masatoshi; Ichihashi, Noriaki

    2012-01-01

    This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis. PMID:21472438

  14. A conserved isoleucine maintains the inactive state of Bruton’s tyrosine kinase

    PubMed Central

    Boyken, Scott E.; Chopra, Nikita; Xie, Qian; Joseph, Raji E.; Wales, Thomas E.; Fulton, D. Bruce; Engen, John R.; Jernigan, Robert L.; Andreotti, Amy H.

    2014-01-01

    Despite high homology among non-receptor tyrosine kinases, different kinase families employ a diverse array of regulatory mechanisms. For example, the catalytic kinase domains of the Tec family kinases are inactive without assembly of the adjacent regulatory domains, whereas the Src kinase domains are autoinhibited by the assembly of similar adjacent regulatory domains. Using molecular dynamic simulations, biochemical assays, and biophysical approaches, we have uncovered an isoleucine residue in the kinase domain of the Tec family member Btk that, when mutated to the closely related leucine, leads to a shift in the conformational equilibrium of the kinase domain toward the active state. The single amino acid mutation results in measureable catalytic activity for the Btk kinase domain in the absence of the regulatory domains. We suggest this isoleucine side chain in the Tec family kinases acts as a ‘wedge’ that restricts the conformational space available to key regions in the kinase domain, preventing activation until the kinase domain associates with its regulatory subunits and overcomes the energetic barrier to activation imposed by the isoleucine side chain. PMID:25193673

  15. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals.

    PubMed Central

    Yoshida, A; Huang, I Y; Ikawa, M

    1984-01-01

    Usual human livers contain two major aldehyde dehydrogenase [(ALDH) aldehyde:NAD+ oxidoreductase] isozymes--i.e., a cytosolic ALDH1 component and a mitochondrial ALDH2 component--whereas approximately equal to 50% of Orientals are "atypical" and have only the ALDH1 isozyme and are missing the ALDH2 isozyme. We previously demonstrated that atypical livers contain an enzymatically inactive but immunologically crossreactive material (CRM) corresponding to the ALDH2 component. The enzymatically active ALDH2 obtained from a usual liver and the CRM obtained from an atypical liver were reduced, S-carboxymethylated, and digested by trypsin. Separation of their digests by high-performance reverse-phase chromatography and by two-dimensional paper chromatography and electrophoresis revealed that ALDH2 contained a peptide sequence of -Glu-Leu-Gly-Glu-Ala-Gly-Leu-Gln-Ala-Asn-Val-Gln-Val-Lys- and that the glutamine adjacent to lysine was substituted by lysine in CRM. All other tryptic peptides, including eight peptides containing S-carboxymethylcysteine, were common in ALDH2 and CRM. It is concluded that a point mutation in the human ALDH2 locus produced the glutamine leads to lysine substitution and enzyme inactivation. Images PMID:6582480

  16. Emergent ultra–long-range interactions between active particles in hybrid active–inactive systems

    NASA Astrophysics Data System (ADS)

    Steimel, Joshua P.; Aragones, Juan L.; Hu, Helen; Qureshi, Naser

    2016-04-01

    Particle–particle interactions determine the state of a system. Control over the range of such interactions as well as their magnitude has been an active area of research for decades due to the fundamental challenges it poses in science and technology. Very recently, effective interactions between active particles have gathered much attention as they can lead to out-of-equilibrium cooperative states such as flocking. Inspired by nature, where active living cells coexist with lifeless objects and structures, here we study the effective interactions that appear in systems composed of active and passive mixtures of colloids. Our systems are 2D colloidal monolayers composed primarily of passive (inactive) colloids, and a very small fraction of active (spinning) ferromagnetic colloids. We find an emergent ultra–long-range attractive interaction induced by the activity of the spinning particles and mediated by the elasticity of the passive medium. Interestingly, the appearance of such interaction depends on the spinning protocol and has a minimum actuation timescale below which no attraction is observed. Overall, these results clearly show that, in the presence of elastic components, active particles can interact across very long distances without any chemical modification of the environment. Such a mechanism might potentially be important for some biological systems and can be harnessed for newer developments in synthetic active soft materials.

  17. Jasmonate signaling in plant stress responses and development - active and inactive compounds.

    PubMed

    Wasternack, Claus; Strnad, Miroslav

    2016-09-25

    Jasmonates (JAs) are lipid-derived signals mediating plant responses to biotic and abiotic stresses and in plant development. Following the elucidation of each step in their biosynthesis and the important components of perception and signaling, several activators, repressors and co-repressors have been identified which contribute to fine-tuning the regulation of JA-induced gene expression. Many of the metabolic reactions in which JA participates, such as conjugation with amino acids, glucosylation, hydroxylation, carboxylation, sulfation and methylation, lead to numerous compounds with different biological activities. These metabolites may be highly active, partially active in specific processes or inactive. Hydroxylation, carboxylation and sulfation inactivate JA signaling. The precursor of JA biosynthesis, 12-oxo-phytodienoic acid (OPDA), has been identified as a JA-independent signaling compound. An increasing number of OPDA-specific processes is being identified. To conclude, the numerous JA compounds and their different modes of action allow plants to respond specifically and flexibly to alterations in the environment. PMID:26581489

  18. Active and Inactive Transplacement of the M26 Recombination Hotspot in Schizosaccharomyces Pombe

    PubMed Central

    Virgin, J. B.; Metzger, J.; Smith, G. R.

    1995-01-01

    The ade6-M26 mutation of the fission yeast Schizosaccharomyces pombe creates a meiotic recombination hotspot that elevates ade6 intragenic recombination ~10-15-fold. A heptanucleotide sequence including the M26 point mutation is required but not sufficient for hotspot activity. We studied the effects of plasmid and chromosomal context on M26 hotspot activity. The M26 hotspot was inactive on a multicopy plasmid containing M26 embedded within 3.0 or 5.9 kb of ade6 DNA. Random S. pombe genomic fragments totaling ~7 Mb did not activate the M26 hotspot on a plasmid. M26 hotspot activity was maintained when 3.0-, 4.4-, and 5.9-kb ade6-M26 DNA fragments, with various amounts of non-S. pombe plasmid DNA, were integrated at the ura4 chromosomal locus, but only in certain configurations relative to the ura4 gene and the cointegrated plasmid DNA. Several integrations created new M26-independent recombination hotspots. In all cases the non-ade6 DNA was located >1 kb from the M26 site, and in some cases >2 kb. Because the chromosomal context effect was transmitted over large distances, and did not appear to be mediated by a single discrete DNA sequence element, we infer that the local chromatin structure has a pronounced effect on M26 hotspot activity. PMID:8536980

  19. Factors associated with leisure time physical inactivity in black individuals: hierarchical model

    PubMed Central

    Lessa, Ines; Barbosa, Paulo José B.; Barbosa, Simone Janete O.; Costa, Maria Cecília; Lopes, Adair da Silva

    2014-01-01

    Background. A number of studies have shown that the black population exhibits higher levels of leisure-time physical inactivity (LTPI), but few have investigated the factors associated with this behavior. Objective. The aim of this study was to analyze associated factors and the explanatory model proposed for LTPI in black adults. Methods. The design was cross-sectional with a sample of 2,305 adults from 20–96 years of age, 902 (39.1%) men, living in the city of Salvador, Brazil. LTPI was analyzed using the International Physical Activity Questionnaire (IPAQ). A hierarchical model was built with the possible factors associated with LTPI, distributed in distal (age and sex), intermediate 1 (socioeconomic status, educational level and marital status), intermediate 2 (perception of safety/violence in the neighborhood, racial discrimination in private settings and physical activity at work) and proximal blocks (smoking and participation in Carnival block rehearsals). We estimated crude and adjusted odds ratio (OR) using logistic regression. Results. The variables inversely associated with LTPI were male gender, socioeconomic status and secondary/university education, although the proposed model explains only 4.2% of LTPI. Conclusions. We conclude that male gender, higher education and socioeconomic status can reduce LTPI in black adults. PMID:25289177

  20. A novel large filamentous deltaproteobacterium on hydrothermally inactive sulfide chimneys of the Southern Mariana Trough

    NASA Astrophysics Data System (ADS)

    Kato, Shingo; Yamagishi, Akihiko

    2016-04-01

    Unusual large filamentous bacteria (LFB) have been found on the deep seafloor environments. They play a significant role in geochemical cycling in the dark environments. However, our knowledge of the spatial distribution and phylogenetic diversity of the LFB on the deep seafloor are still limited due to the inaccessibility to these environments. Here, we report the discovery of a novel LFB on a hydrothermally inactive sulfide chimney in a deep-sea hydrothermal field of the Southern Mariana Trough. Light and electron microscopic observation showed that the width and total length of the LFB were >8 μm and >100 μm, respectively, of which morphology was similar to that of other known LFB such as "cable bacteria" of the Desulfobulbaceae. Analyses of a 16S rRNA gene clone library and fluorescence in situ hybridization revealed that this LFB belongs to the Desulfobulbaceae. The 16S rRNA gene of the LFB showed 94% similarity to those of the reported cable bacteria and cultured deltaproteobacterial species, suggesting that the LFB is a novel cable bacterium of the Desulfobulbaceae. The novel LFB potentially play a role in sulfur cycling on sulfide chimneys at the hydrothermally ceasing or even ceased deep-sea hydrothermal fields.

  1. Engineering study of 50 miscellaneous inactive underground radioactive waste tanks located at the Hanford Site, Washington

    SciTech Connect

    Freeman-Pollard, J.R.

    1994-03-02

    This engineering study addresses 50 inactive underground radioactive waste tanks. The tanks were formerly used for the following functions associated with plutonium and uranium separations and waste management activities in the 200 East and 200 West Areas of the Hanford Site: settling solids prior to disposal of supernatant in cribs and a reverse well; neutralizing acidic process wastes prior to crib disposal; receipt and processing of single-shell tank (SST) waste for uranium recovery operations; catch tanks to collect water that intruded into diversion boxes and transfer pipeline encasements and any leakage that occurred during waste transfer operations; and waste handling and process experimentation. Most of these tanks have not been in use for many years. Several projects have, been planned and implemented since the 1970`s and through 1985 to remove waste and interim isolate or interim stabilize many of the tanks. Some tanks have been filled with grout within the past several years. Responsibility for final closure and/or remediation of these tanks is currently assigned to several programs including Tank Waste Remediation Systems (TWRS), Environmental Restoration and Remedial Action (ERRA), and Decommissioning and Resource Conservation and Recovery Act (RCRA) Closure (D&RCP). Some are under facility landlord responsibility for maintenance and surveillance (i.e. Plutonium Uranium Extraction [PUREX]). However, most of the tanks are not currently included in any active monitoring or surveillance program.

  2. Sequence of the phosphothreonyl regulatory site peptide from inactive maize leaf pyruvate, orthophosphate dikinase

    SciTech Connect

    Roeske, C.A.; Kutny, R.M.; Budde, R.J.A.; Chollet, R.

    1988-05-15

    The regulatory site peptide sequence of phosphorylated inactive pyruvate, orthophosphate dikinase from maize leaf tissue was determined by automated Edman degradation analysis of /sup 32/P-labeled peptides purified by reversed-phase high performance liquid chromatography. The overlapping phosphopeptides were products of a digestion of the (..beta..-/sup 32/P)ADP-inactivated dikinase with either trypsin or Pronase E. The sequence is Thr-Glu-Arg-Gly-Gly-Met-Thr(P)-Ser-His-Ala-Ala-Val-Val-Ala-Arg. The phosphothreonine residue, which appeared as either an anomalous proline or an unidentifiable phenylthiohydantoin derivative during sequencing, was verified by two-dimensional phosphoamino acid analysis of the phosphopeptides and by resequencing the tryptic peptide after dephosphorylation with exogenous alkaline phosphatase. This sequence, starting at position 4, is completely homologous to the previously published sequence of the tryptic dodecapeptide harboring the catalytically essential (phospho)histidyl residue in the active-site domain of the dikinase from the nonphotosynthetic bacterium, Bacteroides symbiosus. These comparative results indicate that the regulatory phosphothreonine causing complete inactivation of maize leaf dikinase is separated from the critical active-site (phospho)histidine by just one intervening residue in the primary sequence.

  3. Radiological survey of the inactive uranium-mill tailings at Lakeview, Oregon

    SciTech Connect

    Haywood, F.F.; Burden, J.E.; Ellis, B.S.; Loy, E.T.; Shinpaugh, W.H.

    1980-06-01

    The results of the radiological survey of the inactive uranium-mill site at Lakeview, Oregon, show that the average gamma-ray exposure rate 1 m above the tailings pile and the evaporation pond area (now dry) is close to the average background level for the area (11 ..mu..R/hr). The /sup 226/Ra concentration in most of the surface soil and sediment samples is also at or below the average background value for surface soil samples in the area (0.8 pCi/g). Calculated /sup 226/Ra concentrations, based on gamma radiation measurements in shallow (1-m-deep) holes, are in agreement with the results of surface soil and sediment analyses and with gamma-ray exposure rate measurements. The tailings at this site have been stabilized by the addition of 46 to 60 cm (18 to 24 in.) of soil that supports vigorous growth of vegetation. This treatment, coupled with a low-level inventory of /sup 226/Ra in the tailings (50 Ci), has resulted in limited spread of tailings by wind and water.

  4. Emergent Ultra-Long-Range Interactions Between Active Particles in Hybrid Active-Inactive Systems

    NASA Astrophysics Data System (ADS)

    Steimel, Joshua; Aragones, Juan; Hu, Helen; Qureshi, Naser; Alexander-Katz, Alfredo

    Particle-particle interactions determine the state of a system. Control over the range and magnitude of such interactions has been an active area of research for decades due to the fundamental challenges it poses in science and technology. Effective interactions between active particles have gathered much attention as they can lead to out-of-equilibrium cooperative states such as flocking. Inspired by nature, where active living cells coexist with lifeless, immobile objects and structures, here we study the effective interactions that appear in systems composed of active and passive mixtures of colloids. Our system is a two dimensional colloidal monolayer composed primarily of passive (inactive) colloids and a very small fraction of active (sinning) ferromagnetic colloids. We find an emergent ultra-long-range attractive interaction between active particles induced by the activity of the spinning particles and mediated by the elasticity of the passive medium. Interestingly, the appearance of such interaction depends on the spinning protocol and has a minimum actuation time scale below which no attraction is observed. Overall, these results clearly show that in the presence of elastic components, active particles can interact across very long distances without any chemical modification of the environment. Such a mechanism might potentially be important for some biological systems and can be harnessed for newer developments in synthetic active soft materials.

  5. The crystal structure of an inactive dimer of PDZ-binding kinase.

    PubMed

    Dong, Chunming; Tang, Xue; Xie, Ying; Zou, Qingwei; Yang, Xue; Zhou, Hao

    2016-08-01

    The overexpression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) has been associated with hematologic tumors, breast cancer and various other cancers. However, the three-dimensional structure of PBK has not been solved. In this study, we determined the crystal structure of human PBK, which has two phospho-mimicking mutations T9E and T198E. The structural data indicated that PBK may assemble into an inactive dimer in alkaline conditions. Analytical size-exclusion chromatography and analytical ultracentrifugation confirmed that PBK exists in a conformational transition between dimers and monomers at different pH conditions. Co-IP and kinase assays suggested that the active state of PBK is a monomer and does not form a dimer even under alkaline conditions. These results showed that the conformational transition of PBK is important for its kinase activity regulation. Collectively, our observations may provide a novel starting point for structure-based functional studies. PMID:27262437

  6. The dragons of inaction: psychological barriers that limit climate change mitigation and adaptation.

    PubMed

    Gifford, Robert

    2011-01-01

    Most people think climate change and sustainability are important problems, but too few global citizens engaged in high-greenhouse-gas-emitting behavior are engaged in enough mitigating behavior to stem the increasing flow of greenhouse gases and other environmental problems. Why is that? Structural barriers such as a climate-averse infrastructure are part of the answer, but psychological barriers also impede behavioral choices that would facilitate mitigation, adaptation, and environmental sustainability. Although many individuals are engaged in some ameliorative action, most could do more, but they are hindered by seven categories of psychological barriers, or "dragons of inaction": limited cognition about the problem, ideological world views that tend to preclude pro-environmental attitudes and behavior, comparisons with key other people, sunk costs and behavioral momentum, discredence toward experts and authorities, perceived risks of change, and positive but inadequate behavior change. Structural barriers must be removed wherever possible, but this is unlikely to be sufficient. Psychologists must work with other scientists, technical experts, and policymakers to help citizens overcome these psychological barriers. PMID:21553954

  7. Growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus Selenka during periods of inactivity

    NASA Astrophysics Data System (ADS)

    Du, Rongbin; Zang, Yuanqi; Tian, Xiangli; Dong, Shuanglin

    2013-03-01

    The growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus, were investigated during periods of inactivity. The body weight, oxygen consumption rate (OCR), activities of acidic phosphatase (ACP), alkaline phosphatase (AKP), catalase (CAT) and superoxide dismutase (SOD), and content of heat shock protein 70 (Hsp70) in the body wall and coelomic fluid of A. japonicus were measured during starvation, experimental aestivation and aestivation. The results showed that the body weight of sea cucumber in the three treatments decreased significantly during the experimental period ( P < 0.05). The OCR of sea cucumber reduced in starvation and experimental aestivation treatments, but increased gradually in natural aestivation treatment. The activities of ACP and AKP of sea cucumber decreased gradually in all treatments, whereas those of SOD and CAT as well as Hsp70 content decreased in the starvation and experimental aestivation treatments and increased in natural aestivation treatment. The sea cucumber entered a state of aestivation at 24°C. To some extent, the animals in experimental aestivation were different from those in natural aestivation in metabolism and physiological response. These findings suggested that the aestivation mechanism of A. japonicus is complex and may not be attributed to the elevated temperature only.

  8. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

    PubMed Central

    Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga; Stamenova, Elena K.; Durand, Neva C.; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L.; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P.; Lander, Eric S.; Chadwick, Brian P.; Aiden, Erez Lieberman

    2016-01-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called “superdomains,” such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called “superloops.” DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  9. High Levels of Physical Inactivity Amongst Dental Professionals: A Questionnaire Based Cross Sectional Study

    PubMed Central

    Shivlingesh, KK; Jayaprakash, K; Gupta, Bhuvandeep; Gupta, Neha; Anand, Richa; Motghare, Vaibhav; Prabhakar, Ishan

    2015-01-01

    Introduction: A Dentist plays an important role in providing health education (General and Oral) to the community. Questions arise regarding their own health, which in turn affects their patients’ counselling for leading a healthy and a physically active life. Aim: To measure and compare the amount of physical activity present amongst dental professionals with the general population of Greater Noida. Materials and Methods: The International Physical Activity Questionnaire (IPAQ) was used to measure physical activity and statistical significance was calculated using SPSS version 21.0. Statistical significance was kept as p <.05. Results: Compared to the general population, Dentists were more obese and reported increased levels of low physical activity. Dentists had an increased and significant transportation and leisure time activity (p= .03 and .01) whereas, the general population had a higher level of vigorous activity(p = <.01). The MET hour/week for dentists and general population was 33.72 and 36.24 respectively, which was quite low as compared to European population. Conclusion: The results indicate that dentists report a lower level of physical activity as compared to the general population of Greater Noida. However, on a global scale, the physical inactiveness of dentists and general population alike could pose a serious health hazard and if kept unchecked, shall increase the global burden of chronic disease. PMID:25738085

  10. Effects of Tagetes patula on Active and Inactive Stages of Root-Knot Nematodes.

    PubMed

    Marahatta, Sharadchandra P; Wang, Koon-Hui; Sipes, Brent S; Hooks, Cerruti R R

    2012-03-01

    Although marigold (Tagetes patula) is known to produce allelopathic compounds toxic to plant-parasitic nematodes, suppression of Meloidogyne incognita can be inconsistent. Two greenhouse experiments were conducted to test whether marigold is more effective in suppressing Meloidogyne spp. when it is active rather than dormant. Soils infested with Meloidogyne spp. were collected and conditioned in the greenhouse either by 1) keeping the soil dry (DRY), 2) irrigating with water (IRR), or 3) drenching with cucumber (Cucumis sativus) leachate (CL) for 5 wk. These soils were then either planted with cucumber, marigold or remained bare for 10 wk. Suppression of nematode by marigold was then assayed using cucumber. DRY conditioning resulted in the highest number of inactive nematodes, whereas CL and IRR had higher numbers of active nematodes than DRY. At the end of the cucumber bioassay, marigold suppressed the numbers of Meloidogyne females in cucumber roots if the soil was conditioned in IRR or CL, but not in DRY. However, in separate laboratory assays, marigold root leachate slightly reduced M. incognita J2 activity but did not reduce egg hatch (P > 0.05). These finding suggest that marigold can only suppress Meloidogyne spp. when marigold is actively growing. This further suggests that marigold will more efficiently suppress Meloidogyne spp. if planted when these nematodes are in active stage. PMID:23482862

  11. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.

    PubMed

    Darrow, Emily M; Huntley, Miriam H; Dudchenko, Olga; Stamenova, Elena K; Durand, Neva C; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P; Lander, Eric S; Chadwick, Brian P; Aiden, Erez Lieberman

    2016-08-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  12. Investigation of contamination of earthen covers on inactive uranium mill tailings

    SciTech Connect

    Markos, G.; Bush, K.J.

    1983-01-01

    The upward migration of contaminants into earthen covers on uranium mill tailings was evaluated from chemical and isotopic analysis of samples from 5--10 cm intervals through the cover and into the tailings at three locations on the Riverton pile. The Uranium Mill Tailings Remedial Action Project elected to determine the significance of migration of salts and contaminants into earthen covers emplaced on tailings by funding this investigation of the migration which has occurred through an earthen cover since the time of emplacement on an inactive uranium mill tailings pile. The Riverton tailings pile, covered with 20 to 40 cm of local sandy soil, was chosen for the study. The objectives of the study were to: determine vertical distributions of concentrations of salts, trace metals, and radionuclides through the cover and into the tailings; determine the concentrations of salts and contaminants in the cover from chemical migration; relate the migration of salts to the contaminants; model the mechanisms responsible for promoting and retarding migration; and evaluate the chemical and physical properties of the cover influencing migration. 20 refs., 35 figs., 10 tabs.

  13. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults

    PubMed Central

    Yang, Chih-Hsiang; Maher, Jaclyn P.; Conroy, David E.

    2015-01-01

    Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October–November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID:26844135

  14. Anthropometric determinants of rowing ergometer performance in physically inactive collegiate females.

    PubMed

    Podstawski, R; Choszcz, Dj; Konopka, S; Klimczak, J; Starczewski, M

    2014-12-01

    The aim of the study was to evaluate anthropometric characteristics as determinants of 500 m rowing ergometer performance in physically inactive collegiate females. In this cross-sectional study, which included 196 collegiate females aged 19-23 years not participating in regular physical activities, body mass (BM), body height (BH), length of upper limbs (LA), length of lower limbs (LL), body mass index (BMI), slenderness index (SI), and the Choszcz-Podstawski index (CPI) were measured and a stepwise multiple regression analysis was performed. Participants performed 500 m maximal effort on a Concept II rowing ergometer. BM, BH, LA, LL, and the BMI, SI and CPI indices were found to be statistically significant determinants of 500 m performance. The best results (T) were achieved by females whose BH ranged from 170 to 180 cm, with LA and LL ranging from 75 to 80 cm and 85 to 90 cm, respectively. The best fitting statistical model was identified as: T = 11.6793 LR - 0.1130 LR (2) - 0.0589 LN (2) + 29.2157 CPI(2) + 0.1370 LR·LN - 2.6926 LR·CPI - 211.7796. This study supports a need for additional studies focusing on understanding the importance of anthropometric differences in rowing ergometer performance, which could lead to establishing a better quality reference for evaluation of cardiorespiratory fitness tested using a rowing ergometer in collegiate females. PMID:25609890

  15. Emergent ultra-long-range interactions between active particles in hybrid active-inactive systems.

    PubMed

    Steimel, Joshua P; Aragones, Juan L; Hu, Helen; Qureshi, Naser; Alexander-Katz, Alfredo

    2016-04-26

    Particle-particle interactions determine the state of a system. Control over the range of such interactions as well as their magnitude has been an active area of research for decades due to the fundamental challenges it poses in science and technology. Very recently, effective interactions between active particles have gathered much attention as they can lead to out-of-equilibrium cooperative states such as flocking. Inspired by nature, where active living cells coexist with lifeless objects and structures, here we study the effective interactions that appear in systems composed of active and passive mixtures of colloids. Our systems are 2D colloidal monolayers composed primarily of passive (inactive) colloids, and a very small fraction of active (spinning) ferromagnetic colloids. We find an emergent ultra-long-range attractive interaction induced by the activity of the spinning particles and mediated by the elasticity of the passive medium. Interestingly, the appearance of such interaction depends on the spinning protocol and has a minimum actuation timescale below which no attraction is observed. Overall, these results clearly show that, in the presence of elastic components, active particles can interact across very long distances without any chemical modification of the environment. Such a mechanism might potentially be important for some biological systems and can be harnessed for newer developments in synthetic active soft materials. PMID:27071096

  16. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults.

    PubMed

    Yang, Chih-Hsiang; Maher, Jaclyn P; Conroy, David E

    2015-01-01

    Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October-November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID:26844135

  17. Dietary carbohydrates, physical inactivity, obesity, and the 'metabolic syndrome' as predictors of coronary heart disease.

    PubMed

    Liu, S; Manson, J E

    2001-08-01

    Several decades of epidemiological and clinical research have identified physical inactivity, excessive calorie consumption, and excess weight as common risk factors for both type 2 diabetes mellitus and coronary heart disease. This trio forms the environmental substrate for a now well-recognized metabolic phenotype called the insulin resistance syndrome. Recent data suggest that a high intake of rapidly absorbed carbohydrates, which is characterized by a high glycemic load (a measure of carbohydrate quality and quantity), may increase the risk of coronary heart disease by aggravating glucose intolerance and dyslipidemia. These data also suggest that individuals who are obese and insulin resistant are particularly prone to the adverse effects of a high dietary glycemic load. In addition, data continue to accumulate suggesting the important beneficial effects of physical activity, even at moderate levels, and weight reduction on improving insulin sensitivity and reducing the risk of coronary heart disease. Future metabolic studies should continue to quantify the physiological impact of different foods on serum glucose and insulin, and such information should routinely be incorporated into large-scale and long-term prospective studies, in which the possible interaction effects between diet and other metabolic determinants such as physical activity and obesity can be examined. Until more definitive data are available, replacing refined grain products and potatoes with minimally processed plant-based foods such as whole grains, fruits, and vegetables, and reducing the intake of high glycemic load beverages may offer a simple strategy for reducing the incidence of coronary heart disease. PMID:11507324

  18. Heterometallic triiron-oxo/hydroxo clusters: effect of redox-inactive metals.

    PubMed

    Herbert, David E; Lionetti, Davide; Rittle, Jonathan; Agapie, Theodor

    2013-12-26

    A series of tetranuclear oxo/hydroxo clusters comprised of three Fe centers and a redox-inactive metal (M) of various charge is reported. Crystallographic studies show an unprecedented Fe3M(μ4-O)(μ2-OH) core that remains intact upon changing M or the oxidation state of iron. Electrochemical studies reveal that the reduction potentials (E1/2) span a window of 500 mV and depend upon the Lewis acidity of M. Using the pKa of the M-aqua complex as a measure of Lewis acidity, these compounds display a linear dependence between E1/2 and acidity, with a slope of ∼70 mV per pKa unit. The current study of [Fe3MO(OH)] and previous ones of [Mn3MOn] (n = 2,4) moieties support the generality of the above relationship between the reduction potentials of heterometallic oxido clusters and the Lewis acidity of incorporated cations, as applied to clusters of different redox-active metals. PMID:24304416

  19. Analysis of DNase 1 sensitivity and methylation of active and inactive X chromosomes of kangaroos (Macropus robustus) by in situ nick translation.

    PubMed

    Loebel, D A; Johnston, P G

    1993-01-01

    The overall nuclease sensitivity and methylation of active and inactive X chromosomes of kangaroos were examined by in situ nick translation. Cultured fibroblasts of subspecies wallaroo-euro (Macropus robustus robustus; Macropus robustus erubescens) hybrids were used, enabling the paternally and maternally derived X chromosomes to be distinguished. No difference was found between the active and inactive X chromosomes with DNase I or MspI digestion. When chromosomes were digested with the methylation sensitive restriction enzymes HpaII and HhaI, the inactive X chromosome was labelled to a greater extent. These results indicate no overall difference in chromatin condensation between the active and inactive X chromosomes and greater overall methylation of the active X chromosome. This relative undermethylation of the inactive X chromosome may be important in X chromosome inactivation, but its function, if any, remains to be determined. PMID:8381740

  20. Poliovirus: Generation and Characterization of Mutants

    PubMed Central

    Burrill, Cecily P.; Strings, Vanessa R.; Schulte, Michael B.; Andino, Raul

    2016-01-01

    Poliovirus (PV) is the prototypical picornavirus. It is a non-enveloped RNA virus with a small (~7.5 kb) genome of positive polarity. cDNA clones of several strains are available, and infectious virus can be produced by the transfection of in vitro transcribed viral genomes into an appropriate host cell. The ease of genetic studies in poliovirus is a primary reason that it has long served as a model to study RNA virus biology, pathogenesis, and evolution. Protocols for the generation and characterization of PV mutants are presented. A separate unit concerning the production, propagation, quantification, and purification of PV will also be presented. PMID:23686829

  1. Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.

    PubMed

    Hu, Jianping; Feng, Zhiwei; Ma, Shifan; Zhang, Yu; Tong, Qin; Alqarni, Mohammed Hamed; Gou, Xiaojun; Xie, Xiang-Qun

    2016-06-27

    Cannabinoid receptor 2 (CB2), a G protein-coupled receptor (GPCR), is a promising target for the treatment of neuropathic pain, osteoporosis, immune system, cancer, and drug abuse. The lack of an experimental three-dimensional CB2 structure has hindered not only the development of studies of conformational differences between the inactive and active CB2 but also the rational discovery of novel functional compounds targeting CB2. In this work, we constructed models of both inactive and active CB2 by homology modeling. Then we conducted two comparative 100 ns molecular dynamics (MD) simulations on the two systems-the active CB2 bound with both the agonist and G protein and the inactive CB2 bound with inverse agonist-to analyze the conformational difference of CB2 proteins and the key residues involved in molecular recognition. Our results showed that the inactive CB2 and the inverse agonist remained stable during the MD simulation. However, during the MD simulations, we observed dynamical details about the breakdown of the "ionic lock" between R131(3.50) and D240(6.30) as well as the outward/inward movements of transmembrane domains of the active CB2 that bind with G proteins and agonist (TM5, TM6, and TM7). All of these results are congruent with the experimental data and recent reports. Moreover, our results indicate that W258(6.48) in TM6 and residues in TM4 (V164(4.56)-L169(4.61)) contribute greatly to the binding of the agonist on the basis of the binding energy decomposition, while residues S180-F183 in extracellular loop 2 (ECL2) may be of importance in recognition of the inverse agonist. Furthermore, pharmacophore modeling and virtual screening were carried out for the inactive and active CB2 models in parallel. Among all 10 hits, two compounds exhibited novel scaffolds and can be used as novel chemical probes for future studies of CB2. Importantly, our studies show that the hits obtained from the inactive CB2 model mainly act as inverse agonist(s) or neutral

  2. Inactive excitations in Mukherjee's state-specific multireference coupled cluster theory treated with internal contraction: Development and applications

    NASA Astrophysics Data System (ADS)

    Das, Sanghamitra; Pathak, Shubhrodeep; Datta, Dipayan; Mukherjee, Debashis

    2012-04-01

    One generic difficulty of most state-specific many-body formalisms using the Jeziorski-Monkhorst ansatz: ψ = ∑μexp (Tμ)|ϕμ⟩cμ for the wave-operators is the large number of redundant cluster amplitudes. The number of cluster amplitudes up to a given rank is many more in number compared to the dimension of the Hilbert Space spanned by the virtual functions of up to the same rank of excitations. At the same time, all inactive excitations - though linearly independent - are far too numerous. It is well known from the success of the contracted multi-reference configuration interaction (MRCI(SD)) that, at least for the inactive double excitations, their model space dependence (μ-dependence) is weak. Considerable simplifications can thus be obtained by using a partially internally contracted description, which uses the physically appealing approximation of taking the inactive excitations Ti to be independent of the model space labels (μ-independent). We propose and implement in this paper such a formalism with internal contractions for inactive excitations (ICI) within Mukherjee's state-specific multi-reference coupled cluster theory (SS-MRCC) framework (referred to from now on as the ICI-SS-MRCC). To the extent the μ-independence of Ti is valid, we expect the ICI-SS-MRCC to retain the conceptual advantages of size-extensivity yet using a drastically reduced number of cluster amplitudes without sacrificing accuracy. Moreover, greater coupling is achieved between the virtual functions reached by inactive excitations as a result of the internal contraction while retaining the original coupling term for the μ-dependent excitations akin to the parent theory. Another major advantage of the ICI-SS-MRCC, unlike the other analogous internally contracted theories, such as IC-MRCISD, CASPT2, or MRMP2, is that it can use relaxed coefficients for the model functions. However, at the same time it employs projection manifolds for the virtuals obtained from inactive n hole

  3. Auxin physiology of the tomato mutant diageotropica

    NASA Technical Reports Server (NTRS)

    Daniel, S. G.; Rayle, D. L.; Cleland, R. E.

    1989-01-01

    The tomato (Lycopersicon esculentum, Mill.) mutant diageotropica (dgt) exhibits biochemical, physiological, and morphological abnormalities that suggest the mutation may have affected a primary site of auxin perception or action. We have compared two aspects of the auxin physiology of dgt and wild-type (VFN8) seedlings: auxin transport and cellular growth parameters. The rates of basipetal indole-3-acetic acid (IAA) polar transport are identical in hypocotyl sections of the two genotypes, but dgt sections have a slightly greater capacity for IAA transport. 2,3,5-Triiodobenzoic acid and ethylene reduce transport in both mutant and wild-type sections. The kinetics of auxin uptake into VFN8 and dgt sections are nearly identical. These results make it unlikely that an altered IAA efflux carrier or IAA uptake symport are responsible for the pleiotropic effects resulting from the dgt mutation. The lack of auxin-induced cell elongation in dgt plants is not due to insufficient turgor, as the osmotic potential of dgt cell sap is less (more negative) than that of VFN8. An auxin-induced increase in wall extensibility, as measured by the Instron technique, only occurs in the VFN8 plants. These data suggest dgt hypocotyls suffer a defect in the sequence of events culminating in auxin-induced cell wall loosening.

  4. Auxin physiology of the tomato mutant diageotropical

    SciTech Connect

    Daniel, S.G.; Rayle, D.L. ); Cleland, R.E. )

    1989-11-01

    The tomato (Lycopersicon esculentum, Mill.) mutant diageotropica (dgt) exhibits biochemical, physiological, and morphological abnormalities that suggest the mutation may have affected a primary site of auxin perception or action. We have compared two aspects of the auxin physiology of dgt and wild-type (VFN8) seedlings: auxin transport and cellular growth parameters. The rates of basipetal indole-3-acetic acid (IAA) polar transport are identical in hypocotyl sections of the two genotypes, but dgt sections have a slightly greater capacity for IAA transport. 2,3,5-Triiodobenzoic acid and ethylene reduce transport in both mutant and wild-type sections. The kinetics of auxin uptake into VFN8 and dgt sections are nearly identical. These results make it unlikely that an altered IAA efflux carrier or IAA uptake symport are responsible for the pleiotropic effects resulting from the dgt mutation. The lack of auxin-induced cell elongation in dgt plants is not due to insufficient turgor, as the osmotic potential of dgt cell sap is less (more negative) than that of VFN8. An auxin-induced increase in wall extensibility, as measured by the Instron technique, only occurs in the VFN8 plants. These data suggest dgt hypocotyls suffer a defect in the sequence of events culminating in auxin-induced cell wall loosening.

  5. Mutants of Arabidopsis thaliana with altered phototropism

    NASA Technical Reports Server (NTRS)

    Khurana, J. P.; Poff, K. L.

    1989-01-01

    Thirty five strains of Arabidopsis thaliana (L.) Heynh. have been identified with altered phototropic responses to 450-nm light. Four of these mutants have been more thoroughly characterized. Strain JK224 shows normal gravitropism and "second positive" phototropism. However, while the amplitude for "first positive" phototropism is the same as that in the wild-type, the threshold and fluence for the maximum response in "first positive" phototropism are shifted to higher fluence by a factor of 20-30. This mutant may represent an alteration in the photoreceptor pigment for phototropism. Strain JK218 exhibits no curvature to light at any fluence from 1 micromole m-2 to 2700 micromoles m-2, but shows normal gravitropism. Strain JK345 shows no "first positive" phototropism, and reduced gravitropism and "second positive" phototropism. Strain JK229 shows no measurable "first positive" phototropism, but normal gravitropism and "second positive" phototropism. Based on these data, it is suggested that: 1. gravitropism and phototropism contain at least one common element; 2. "first positive" and "second positive" phototropism contain at least one common element; and 3. "first positive" phototropism can be substantially altered without any apparent alteration of "second positive" phototropism.

  6. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, James P.

    1997-01-01

    Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned.

  7. Method for rapid isolation of sensitive mutants

    DOEpatents

    Freyer, J.P.

    1997-07-29

    Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned. 15 figs.

  8. Isolation of mouse cell proteoglycan mutants

    SciTech Connect

    Keller, K.M.; Keller, J.M.

    1986-05-01

    The sulfated proteoglycans on the surface of cultured mammalian cells have been implicated in a variety of phenomena. To obtain more direct evidence for the role of these molecules in specific cellular functions, they are isolating mutants that produce altered sulfated proteoglycans from a cloned line of Swiss mouse 3T3 cells. This cell type was selected because it exhibits contact inhibition of growth and there is extensive information on its' cell surface and extracellular proteoglycans and other glycoproteins. Cells were chemically mutagenized and subjected to one or more cycles of radiation suicide in the presence of /sup 35/S-sulfate. By replica plating, 150 clones, which appear to incorporate abnormal amounts of /sup 35/S-sulfate, have been selected. After recloning three times via the replica plating technique, the proteoglycans of 29 clones have thus far been analyzed. They have identified four clones which appear to make altered amounts of either cell surface heparan sulfate or chondroitin sulfate. The biochemical bases for the altered levels of the proteoglycans are under study. Of particular interest, however, is the fact that in this limited collection of mutants the chemical alterations correlate with specific altered cellular morphologies.

  9. Too Many Mutants with Multiple Mutations

    PubMed Central

    Drake, John W.

    2007-01-01

    It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These “multiples” appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts. PMID:17687667

  10. Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

    SciTech Connect

    Cook, Melloni N.; Dunning, Jonathan P; Wiley, Ronald G; Chesler, Elissa J; Johnson, Dabney K; Goldowitz, Daniel

    2007-01-01

    We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsiveness to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.

  11. Forward genetic screen for auxin-deficient mutants by cytokinin

    PubMed Central

    Wu, Lei; Luo, Pan; Di, Dong-Wei; Wang, Li; Wang, Ming; Lu, Cheng-Kai; Wei, Shao-Dong; Zhang, Li; Zhang, Tian-Zi; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, Guang-Qin

    2015-01-01

    Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis. PMID:26143750

  12. Synaptic transmission deficits in Caenorhabditis elegans synaptobrevin mutants.

    PubMed

    Nonet, M L; Saifee, O; Zhao, H; Rand, J B; Wei, L

    1998-01-01

    Synaptobrevins are vesicle-associated proteins implicated in neurotransmitter release by both biochemical studies and perturbation experiments that use botulinum toxins. To test these models in vivo, we have isolated and characterized the first synaptobrevin mutants in metazoans and show that neurotransmission is severely disrupted in mutant animals. Mutants lacking snb-1 die just after completing embryogenesis. The dying animals retain some capability for movement, although they are extremely uncoordinated and incapable of feeding. We also have isolated and characterized several hypomorphic snb-1 mutants. Although fully viable, these mutants exhibit a variety of behavioral abnormalities that are consistent with a general defect in the efficacy of synaptic transmission. The viable mutants are resistant to the acetylcholinesterase inhibitor aldicarb, indicating that cholinergic transmission is impaired. Extracellular recordings from pharyngeal muscle also demonstrate severe defects in synaptic transmission in the mutants. The molecular lesions in the hypomorphic alleles reside on the hydrophobic face of a proposed amphipathic-helical region implicated biochemically in interacting with the t-SNAREs syntaxin and SNAP-25. Finally, we demonstrate that double mutants lacking both the v-SNAREs synaptotagmin and snb-1 are phenotypically similar to snb-1 mutants and less severe than syntaxin mutants. Our work demonstrates that synaptobrevin is essential for viability and is required for functional synaptic transmission. However, our analysis also suggests that transmitter release is not completely eliminated by removal of either one or both v-SNAREs. PMID:9412487

  13. Mutants of Downy Mildew Resistance in Lactuca Sativa (Lettuce)

    PubMed Central

    Okubara, P. A.; Anderson, P. A.; Ochoa, O. E.; Michelmore, R. W.

    1994-01-01

    As part of our investigation of disease resistance in lettuce, we generated mutants that have lost resistance to Bremia lactucae, the casual fungus of downy mildew. Using a rapid and reliable screen, we identified 16 distinct mutants of Latuca sativa that have lost activity of one of four different downy mildew resistance genes (Dm). In all mutants, only a single Dm specificity was affected. Genetic analysis indicated that the lesions segregated as single, recessive mutations at the Dm loci. Dm3 was inactivated in nine of the mutants. One of five Dm1 mutants was selected from a population of untreated seeds and therefore carried a spontaneous mutation. All other Dm1, Dm3, Dm5/8 and Dm7 mutants were derived from γ- or fast neutron-irradiated seed. In two separate Dm1 mutants and in each of the eight Dm3 mutants analyzed, at least one closely linked molecular marker was absent. Also, high molecular weight genomic DNA fragments that hybridized to a tightly linked molecular marker in wild type were either missing entirely or were truncated in two of the Dm3 mutants, providing additional evidence that deletions had occurred in these mutants. Absence of mutations at loci epistatic to the Dm genes suggested that such loci were either members of multigene families, were critical for plant survival, or encoded components of duplicated pathways for resistance; alternatively, the genes determining downy mildew resistance might be limited to the Dm loci. PMID:8088530

  14. Mutants of Saccharomyces Cerevisiae with Defects in Acetate Metabolism: Isolation and Characterization of Acn(-) Mutants

    PubMed Central

    McCammon, M. T.

    1996-01-01

    The two carbon compounds, ethanol and acetate, can be oxidatively metabolized as well as assimilated into carbohydrate in the yeast Saccharomyces cerevisiae. The distribution of acetate metabolic enzymes among several cellular compartments, mitochondria, peroxisomes, and cytoplasm makes it an intriguing system to study complex metabolic interactions. To investigate the complex process of carbon catabolism and assimilation, mutants unable to grow on acetate were isolated. One hundred five Acn(-) (``ACetate Nonutilizing'') mutants were sorted into 21 complementation groups with an additional 20 single mutants. Five of the groups have defects in TCA cycle enzymes: MDH1, CIT1, ACO1, IDH1, and IDH2. A defect in RTG2, involved in the retrograde communication between the mitochondrion and the nucleus, was also identified. Four genes encode enzymes of the glyoxylate cycle and gluconeogenesis: ICL1, MLS1, MDH2, and PCK1. Five other genes appear to be defective in regulating metabolic activity since elevated levels of enzymes in several metabolic pathways, including the glyoxylate cycle, gluconeogenesis, and acetyl-CoA metabolism, were detected in these mutants: ACN8, ACN9, ACN17, ACN18, and ACN42. In summary, this analysis has identified at least 22 and as many as 41 different genes involved in acetate metabolism. PMID:8878673

  15. Sim2 mutants have developmental defects not overlapping with those of Sim1 mutants.

    PubMed

    Goshu, Eleni; Jin, Hui; Fasnacht, Rachel; Sepenski, Mike; Michaud, Jacques L; Fan, Chen-Ming

    2002-06-01

    The mouse genome contains two Sim genes, Sim1 and Sim2. They are presumed to be important for central nervous system (CNS) development because they are homologous to the Drosophila single-minded (sim) gene, mutations in which cause a complete loss of CNS midline cells. In the mammalian CNS, Sim2 and Sim1 are coexpressed in the paraventricular nucleus (PVN). While Sim1 is essential for the development of the PVN (J. L. Michaud, T. Rosenquist, N. R. May, and C.-M. Fan, Genes Dev. 12:3264-3275, 1998), we report here that Sim2 mutant has a normal PVN. Analyses of the Sim1 and Sim2 compound mutants did not reveal obvious genetic interaction between them in PVN histogenesis. However, Sim2 mutant mice die within 3 days of birth due to lung atelectasis and breathing failure. We attribute the diminished efficacy of lung inflation to the compromised structural components surrounding the pleural cavity, which include rib protrusions, abnormal intercostal muscle attachments, diaphragm hypoplasia, and pleural mesothelium tearing. Although each of these structures is minimally affected, we propose that their combined effects lead to the mechanical failure of lung inflation and death. Sim2 mutants also develop congenital scoliosis, reflected by the unequal sizes of the left and right vertebrae and ribs. The temporal and spatial expression patterns of Sim2 in these skeletal elements suggest that Sim2 regulates their growth and/or integrity. PMID:12024028

  16. Dietary and Physical Activity/Inactivity Factors Associated with Obesity in School-Aged Children123

    PubMed Central

    Perez-Rodriguez, Marcela; Melendez, Guillermo; Nieto, Claudia; Aranda, Marisol; Pfeffer, Frania

    2012-01-01

    Diet and physical activity (PA) are essential components of nutritional status. Adequate nutrition and an active lifestyle are key factors during childhood, because food habits track into adulthood. Children spend more time in school than in any other environment away from home. Studying the diet factors and patterns of PA that affect obesity risk in children during school hours and the complete school day can help identify opportunities to lower this risk. We directly measured the time children spent performing moderate to vigorous PA (MVPA) at school, compared the amount and intensity of PA during school hours with after-school hours, and tried to determine if diet behaviors and PA or inactivity were associated with excess weight and body fat. This cross-sectional study included 143 normal-weight (NLW) and 48 obese children aged 8–10 y. Diet data were obtained from two 24-h recalls. Body composition was measured by bioimpedance. Screen time and sports participation data were self-reported. NLW children drank/ate more dairy servings than the obese children, who consumed more fruit-flavored water than the NLW group. Consumption of soft drinks, sugar-added juices, and fresh juices was low in both groups. Children were less active during school hours than after school. MVPA was lower during school hours in the obese group than in the NLW group. Schools, parents, and authorities should be more involved in promoting strategies to improve the dietary habits and PA levels of school-aged children, because this group is not achieving the recommended level of daily MVPA. PMID:22798003

  17. Inactive conformation of an insulin despite its wild-type sequence.

    PubMed

    Kurapkat, G; De Wolf, E; Grötzinger, J; Wollmer, A

    1997-03-01

    The peptide group between residues B24 and B25 of insulin was replaced by an ester bond. This modification only in the backbone was meant to eliminate a structurally important H-bond between the amide proton of B25 and the carbonyl oxygen of A19, and consequently to enhance detachment of the C-terminal B-chain from the body of the molecule, exposing the underlying A-chain. According to a model derived from the effects of side-chain substitutions, main-chain shortening, and crosslinking, this conformational change is prerequisite for receptor binding. Contrary to the expectation that increased flexibility would increase receptor binding and activity, depsi-insulin ([B24-B25 CO-O]insulin) has turned out be only 3-4% potent. In search of an explanation for this observation, the solution structure of depsi-insulin was determined by two-dimensional 1H-NMR spectroscopy. It was found that the loss of the B25-A19 H-bond does not entail detachment of the C-terminal B-chain. On the contrary, it is overcompensated by a gain in hydrophobic interaction achieved by insertion of the Phe B25 side chain into the molecule's core. This is possible because of increased rotational freedom in the backbone owing to the ester bond. Distortion of the B20-B23 turn and an altered direction of the distal B-chain are consequences that also affect self-association. The exceptional position of the B25 side chain is thus the key feature of the depsi-insulin structure. Being buried in the interior, it is not available for guiding the interaction with the receptor, a crucial role attributed to it by the model. This seems to be the main reason why the structure of depsi-insulin represents an inactive conformation. PMID:9070440

  18. Inactive conformation of an insulin despite its wild-type sequence.

    PubMed Central

    Kurapkat, G.; De Wolf, E.; Grötzinger, J.; Wollmer, A.

    1997-01-01

    The peptide group between residues B24 and B25 of insulin was replaced by an ester bond. This modification only in the backbone was meant to eliminate a structurally important H-bond between the amide proton of B25 and the carbonyl oxygen of A19, and consequently to enhance detachment of the C-terminal B-chain from the body of the molecule, exposing the underlying A-chain. According to a model derived from the effects of side-chain substitutions, main-chain shortening, and crosslinking, this conformational change is prerequisite for receptor binding. Contrary to the expectation that increased flexibility would increase receptor binding and activity, depsi-insulin ([B24-B25 CO-O]insulin) has turned out be only 3-4% potent. In search of an explanation for this observation, the solution structure of depsi-insulin was determined by two-dimensional 1H-NMR spectroscopy. It was found that the loss of the B25-A19 H-bond does not entail detachment of the C-terminal B-chain. On the contrary, it is overcompensated by a gain in hydrophobic interaction achieved by insertion of the Phe B25 side chain into the molecule's core. This is possible because of increased rotational freedom in the backbone owing to the ester bond. Distortion of the B20-B23 turn and an altered direction of the distal B-chain are consequences that also affect self-association. The exceptional position of the B25 side chain is thus the key feature of the depsi-insulin structure. Being buried in the interior, it is not available for guiding the interaction with the receptor, a crucial role attributed to it by the model. This seems to be the main reason why the structure of depsi-insulin represents an inactive conformation. PMID:9070440

  19. Cardioprotective function of mitochondrial-targeted and transcriptionally inactive STAT3 against ischemia and reperfusion injury.

    PubMed

    Szczepanek, Karol; Xu, Aijun; Hu, Ying; Thompson, Jeremy; He, Jun; Larner, Andrew C; Salloum, Fadi N; Chen, Qun; Lesnefsky, Edward J

    2015-11-01

    Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes a crucial role in protection against ischemia (ISC)-reperfusion (REP) injury by driving expression of anti-apoptotic and anti-oxidant genes. STAT3 is also present in the mitochondria, where it modulates the activity of the electron transport chain (ETC) and the permeability transition pore. Transgenic mice that overexpress a mitochondrial-targeted, transcriptionally inactive STAT3 in cardiomyocytes (MLS-STAT3E mice) exhibit a persistent, partial blockade of electron transfer through complex I that uniquely did not lead to tissue dysfunction at baseline, yet increased mitochondrial ischemic tolerance. The direct contribution of non-transcriptional, mitochondria-localized STAT3 to protection during ISC-REP remains to be established. We hypothesized that the enhanced mitochondrial tolerance to ischemia present in MLS-STAT3E mice would decrease cardiac injury during ISC-REP. In the isolated buffer-perfused heart model, MLS-STAT3E hearts exhibit a decreased infarct size compared to non-transgenic littermate hearts. Contractile recovery, expressed as a percent of LV developed pressure before ISC, is improved in MLS-STAT3E mice. Mitochondria isolated at the end of 60 min. of REP from MLS-STAT3E hearts show attenuated ROS release. The partial and persistent blockade of complex I present in MLS-STAT3E mice decreases cardiac injury during REP, in part via a persistent decrease in ROS production and attenuation of mitochondrial permeability transition pore opening at the onset of REP. In vivo, MLS-STAT3E hearts exhibit substantially higher postoperative survival rate and a substantial decrease in myocardial infarct size. STAT3 mediates cardioprotection not only via canonical action as a transcription factor, but also as a modulator of ETC activity directly in the mitochondria. PMID:26358226

  20. Inactive Disease and Remission in Childhood-onset Systemic Lupus Erythematosus

    PubMed Central

    Mina, Rina; Klein-Gitelman, Marisa S.; Ravelli, Angelo; Beresford, Michael W.; Avcin, Tadej; Espada, Graciela; Eberhard, B. Anne; Schanberg, Laura E.; O’Neil, Kathleen M.; Silva, Clovis A.; Higgins, Gloria C.; Onel, Karen; Singer, Nora G.; von Scheven, Emily; Imundo, Lisa F; Nelson, Shannen; Giannini, Edward H.; Brunner, Hermine I.

    2012-01-01

    Objective To define inactive disease (ID) and clinical remission (CR), and delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE). Methods Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children in ID and 31 children with minimally active lupus (MAL). Results While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for ≥ 6 months and considers treatment. There was consensus that patients in ID/CR can have ≤ 2 mild non-limiting symptoms (i.e. fatigue, arthralgia, headaches or myalgia) but not Raynaud’s phenomenon, chest pain, or objective physical signs of cSLE; ANA positivity and ESR elevation can be present. CBC, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve > 0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL. Conclusions Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE. PMID:22238253

  1. Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis

    PubMed Central

    Yoshimatsu, Yasushi; Yamada, Akihiro; Furukawa, Ryuichi; Sono, Koji; Osamura, Aisaku; Nakamura, Kentaro; Aoki, Hiroshi; Tsuda, Yukiko; Hosoe, Nobuo; Takada, Nobuo; Suzuki, Yasuo

    2015-01-01

    AIM: To evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis (UC). METHODS: Bio-Three tablets, each containing 2 mg of lactomin (Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used as probiotic therapy. Sixty outpatients with UC in remission were randomly assigned to receive 9 Bio-Three tablets/day (Bio-Three group) or 9 placebo tablets/day (placebo group) for 12 mo in addition to their ongoing medications. Clinical symptoms were evaluated monthly or on the exacerbation of symptoms or need for additional medication. Fecal samples were collected to analyze bacterial DNA at baseline and 3-mo intervals. Terminal restriction fragment length polymorphism and cluster analyses were done to examine bacterial components of the fecal microflora. RESULTS: Forty-six patients, 23 in each group, completed the study, and 14 were excluded. The relapse rates in the Bio-Three and placebo groups were respectively 0.0% vs 17.4% at 3 mo (P = 0.036), 8.7% vs 26.1% at 6 mo (P = 0.119), and 21.7% vs 34.8% (P = 0.326) at 9 mo. At 12 mo, the remission rate was 69.5% in the Bio-Three group and 56.6% in the placebo group (P = 0.248). On cluster analysis of fecal flora, 7 patients belonged to cluster I, 32 to cluster II, and 7 to cluster III. CONCLUSION: Probiotics may be effective for maintaining clinical remission in patients with quiescent UC, especially those who belong to cluster I on fecal bacterial analysis. PMID:26019464

  2. Status report for inactive miscellaneous underground storage tanks at Hanford Site 200 Areas

    SciTech Connect

    Powers, T.B.

    1995-10-01

    The purpose of this status report is to summarize updated data and information from the FY 1994 strategy plan that is associated with inactive miscellaneous underground storage tanks (IMUSTs). Assumptions and processes to assess potential risks and operational concerns are documented in this report. Safety issue priorities are ranked based on a number of considerations. Sixty-three IMUSTs have been Identified and placed on the official IMUST list. All the tanks are associated with past Hanford Site operations. Of the 63 tanks., 19 are catch tanks, 20 are vault tanks, 3 are neutralization tanks, 8 are settling tanks, 2 are solvent makeup tanks used to store hexone, 2 are flush tanks, 3 are decontamination tanks, 1 is a diverter station, 1 is a receiver tank, 1 is an experimental tank, and 3 are waste handling tanks. It is important to proactively deal with the risks Imposed by these 63 tanks, and at the same time not jeopardize the existing commitments and schedules for mitigating and resolving identified safety issues related to the 177 SSTs and DSTS. Access controls and signs have been placed on all but the three official IMUSTs added most recently. An accelerated effort to identify authorization documents and perform unreviewed safety question (USQ) screening has been completed. According to a set of criteria consistent with the safety screening data quality objective (DQO) process, 6 IMUSTs are ranked high related to the hydrogen generation potential safety Issue, 1 is ranked high related to the ferrocyanide potential safety issue, 6 are ranked high related to the flammability potential safety issue, and 25 are ranked high related to the vapor emissions potential safety issue.

  3. How to winnow actives from inactives: introducing molecular orthogonal sparse bigrams (MOSBs) and multiclass Winnow.

    PubMed

    Nigsch, Florian; Mitchell, John B O

    2008-02-01

    In the present paper we combine the Winnow algorithm and an advanced scheme for feature generation into a tool for multiclass classification. The Winnow algorithm, specifically designed in the late 1980s to work well with high-dimensional data, by design ignores most of the irrelevant features for the scoring of each single training/test case. To augment the pool of available molecular features we use the Winnow algorithm in conjunction with a process that creates additional features from a set of given ones. We adapt a technique formerly employed in text classification termed "orthogonal sparse bigrams" and extend the use of that method to the domain of cheminformatics. Using circular molecular fingerprints as initial features, we create "molecular orthogonal sparse bigrams" (MOSBs) and report their successful application to the task of classification of bioactive molecules. Additionally, we introduce a memory-efficient way of bagging individual classifiers, avoiding the need to hold the complete training data set in memory. To compare the performance of our method with published results, we use the Hert data set of 8293 active molecules in 11 classes. We compare our method to Random Forest and find that our method not only is comparable or better in classification accuracy (up to 50% higher in MCC [Matthews correlation coefficient], 98% higher in fraction of correct predictions) but also is quicker to train (by a factor between 2 and 18, depending on the feature generation), more memory efficient, and able to cope more easily with large data sets when we seeded the actives into a pool of 94290 inactive molecules. It is shown that this method can be used with different fingerprints. PMID:18220378

  4. Dietary and physical activity/inactivity factors associated with obesity in school-aged children.

    PubMed

    Perez-Rodriguez, Marcela; Melendez, Guillermo; Nieto, Claudia; Aranda, Marisol; Pfeffer, Frania

    2012-07-01

    Diet and physical activity (PA) are essential components of nutritional status. Adequate nutrition and an active lifestyle are key factors during childhood, because food habits track into adulthood. Children spend more time in school than in any other environment away from home. Studying the diet factors and patterns of PA that affect obesity risk in children during school hours and the complete school day can help identify opportunities to lower this risk. We directly measured the time children spent performing moderate to vigorous PA (MVPA) at school, compared the amount and intensity of PA during school hours with after-school hours, and tried to determine if diet behaviors and PA or inactivity were associated with excess weight and body fat. This cross-sectional study included 143 normal-weight (NLW) and 48 obese children aged 8-10 y. Diet data were obtained from two 24-h recalls. Body composition was measured by bioimpedance. Screen time and sports participation data were self-reported. NLW children drank/ate more dairy servings than the obese children, who consumed more fruit-flavored water than the NLW group. Consumption of soft drinks, sugar-added juices, and fresh juices was low in both groups. Children were less active during school hours than after school. MVPA was lower during school hours in the obese group than in the NLW group. Schools, parents, and authorities should be more involved in promoting strategies to improve the dietary habits and PA levels of school-aged children, because this group is not achieving the recommended level of daily MVPA. PMID:22798003

  5. Characterization of arsenic species in microbial mats from an inactive gold mine

    USGS Publications Warehouse

    Foster, A.L.; Ashley, R.P.

    2002-01-01

    Filamentous cyanobacterial mats and Fe oxyhydroxide-rich bacterial mats collected near an inactive gold mine in California are enriched in arsenic (As) approximately 1000-fold relative to the waters in contact with them. The predominant organism in the cyanobacterial mat could not be identified using morphological characteristics, but the unique morphology of the sheath-forming ?? protobacterium Leptothrix ochracea was used to identify this species in Fe oxyhydroxide mat samples from several sites near the gold mine. Leptothrix sheaths commonly exceed 10 ??m in length and have an average diameter of 1 ??m. The Fe-oxyhydroxide mats are dominated by L. ochracea sheaths, but use of fluorescently tagged genetic stains reveals the presence of sheathless bacteria that presumably also promote the formation of Fe oxyhydroxide. X-ray absorption fine structure (XAFS) spectroscopy was used to identify As species in these microbial mats. Mat-associated As is predominantly As(V), even when As(III) is the primary dissolved species in contact with the mats. The species of As(V) associated with the cyanobacterial mat could not be conclusively identified; however, it is not associated with Fe oxyhydroxide or other minerals, based on comparison to XAFS spectra of As adsorbed to various substrates. In addition, the cyanobacterial mat XAFS spectrum is different from that of aqueous As(V), suggesting that As(V) in the mat lacks some or all of the coordinating water molecules present in aqueous solution. We hypothesize that As is associated with the exopolysaccharide (EPS) matrix secreted by the cyanobacteria. In Leptothrix-dominated Fe-oxyhydroxide bacterial mats, XAFS analysis clearly indicates that As(V) is associated with the Fe oxyhydroxide as an adsorbed and/or coprecipitated complex.

  6. Selective Retention of an Inactive Allele of the DKK2 Tumor Suppressor Gene in Hepatocellular Carcinoma.

    PubMed

    Lin, Yung-Feng; Li, Ling-Hui; Lin, Chih-Hung; Tsou, Mei-Hua; Chuang, Ming-Tai Kiffer; Wu, Keh-Ming; Liao, Tsai-Lien; Li, Jian-Chiuan; Wang, Wei-Jie; Tomita, Angela; Tomita, Beverly; Huang, Shiu-Feng; Tsai, Shih-Feng

    2016-05-01

    In an effort to identify the functional alleles associated with hepatocellular carcinoma (HCC), we investigated 152 genes found in the 4q21-25 region that exhibited loss of heterozygosity (LOH). A total of 2,293 pairs of primers were designed for 1,449 exonic and upstream promoter regions to amplify and sequence 76.8-114 Mb on human chromosome 4. Based on the results from analyzing 12 HCC patients and 12 healthy human controls, we discovered 1,574 sequence variations. Among the 99 variants associated with HCC (p < 0.05), four are from the Dickkopf 2 (DKK2) gene: three in the promoter region (g.-967A>T, g.-923C>A, and g.-441T>G) and one in the 5'UTR (c.550T>C). To verify the results, we expanded the subject cohort to 47 HCC cases and 88 healthy controls for conducting haplotype analysis. Eight haplotypes were detected in the non-tumor liver tissue samples, but one major haplotype (TAGC) was found in the tumor tissue samples. Using a reporter assay, this HCC-associated allele registered the lowest level of promoter activity among all the tested haplotype sequences. Retention of this allele in LOH was associated with reduced DKK2 transcription in the HCC tumor tissues. In HuH-7 cells, DKK2 functioned in the Wnt/β-catenin signaling pathway, as an antagonist of Wnt3a, in a dose-dependent manner that inhibited Wnt3a-induced cell proliferation. Taken together, the genotyping and functional findings are consistent with the hypothesis that DKK2 is a tumor suppressor; by selectively retaining a transcriptionally inactive DKK2 allele, the reduction of DKK2 function results in unchecked Wnt/β-catenin signaling, contributing to HCC oncogenesis. Thus our study reveals a new mechanism through which a tumor suppressor gene in a LOH region loses its function by allelic selection. PMID:27203079

  7. Mercury Methylation and Environmental Effects of Inactive Mercury Mines in the Circum-Pacific Region

    NASA Astrophysics Data System (ADS)

    Gray, J. E.

    2001-05-01

    Mercury mines worldwide contain of some the highest concentrations of mercury on earth, and as a result of local mercury contamination, these mines represent areas of environmental concern when mine-drainage enters downstream aquatic systems. The most problematic aspect of mine site mercury contamination is the conversion of inorganic mercury to highly toxic organic mercury compounds, such as methylmercury, and their subsequent uptake by aquatic organisms in surrounding ecosystems. Mercury and methylmercury concentrations were measured in sediment and water samples collected from several inactive mercury mines in Nevada, Alaska, and the Philippines, which are part of the circum-Pacific mineral belt. The mines studied represent different mercury deposit types and sizes, and climatic settings. Geochemical data collected from these mines indicate that areas surrounding hot-springs type mercury deposits generally have lower methylmercury concentrations than silica-carbonate mercury deposits. In hot-springs mercury deposits in Nevada and Alaska, ore is dominantly cinnabar with few acid-water generating minerals such as pyrite, and as a result, mine-water drainage has near neutral pH in which there is low solubility of mercury. Conversely, silica-carbonate deposits, such as Palawan, Philippines, contain abundant cinnabar and pyrite, and the resultant acidic-mine drainage generally has higher concentrations of mercury and methylmercury. Additional factors such as the proximity of mercury mines to wetlands, climatic effects, or mine wastes containing highly soluble mercury compounds potentially enhance mercury methylation. The Palawan mercury mine may be a unique example where several adverse environmental factors produced local mercury contamination, high mercury methylation, fish contamination, and mercury poisoning of humans that consumed these contaminated fish.

  8. The association between cardiorespiratory fitness and abdominal adiposity in postmenopausal, physically inactive South Asian women.

    PubMed

    Lesser, I A; Dick, T J M; Guenette, J A; Hoogbruin, A; Mackey, D C; Singer, J; Lear, S A

    2015-01-01

    In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8-21.8 mL/kg/min), women in the highest tertile (25.0-27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05). We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women. PMID:26844150

  9. Scabies mite inactive serine proteases are potent inhibitors of the human complement lectin pathway.

    PubMed

    Reynolds, Simone L; Pike, Robert N; Mika, Angela; Blom, Anna M; Hofmann, Andreas; Wijeyewickrema, Lakshmi C; Kemp, Dave; Fischer, Katja

    2014-05-01

    Scabies is an infectious skin disease caused by the mite Sarcoptes scabiei and has been classified as one of the six most prevalent epidermal parasitic skin diseases infecting populations living in poverty by the World Health Organisation. The role of the complement system, a pivotal component of human innate immunity, as an important defence against invading pathogens has been well documented and many parasites have an arsenal of anti-complement defences. We previously reported on a family of scabies mite proteolytically inactive serine protease paralogues (SMIPP-Ss) thought to be implicated in host defence evasion. We have since shown that two family members, SMIPP-S D1 and I1 have the ability to bind the human complement components C1q, mannose binding lectin (MBL) and properdin and are capable of inhibiting all three human complement pathways. This investigation focused on inhibition of the lectin pathway of complement activation as it is likely to be the primary pathway affecting scabies mites. Activation of the lectin pathway relies on the activation of MBL, and as SMIPP-S D1 and I1 have previously been shown to bind MBL, the nature of this interaction was examined using binding and mutagenesis studies. SMIPP-S D1 bound MBL in complex with MBL-associated serine proteases (MASPs) and released the MASP-2 enzyme from the complex. SMIPP-S I1 was also able to bind MBL in complex with MASPs, but MASP-1 and MASP-2 remained in the complex. Despite these differences in mechanism, both molecules inhibited activation of complement components downstream of MBL. Mutagenesis studies revealed that both SMIPP-Ss used an alternative site of the molecule from the residual active site region to inhibit the lectin pathway. We propose that SMIPP-Ss are potent lectin pathway inhibitors and that this mechanism represents an important tool in the immune evasion repertoire of the parasitic mite and a potential target for therapeutics. PMID:24854034

  10. Sampling and analysis of the inactive waste tanks TH-2, WC-1, and WC-15

    SciTech Connect

    Autrey, J.W.; Keller, J.M.; Griest, W.H.; Botts, J.L.; Schenley, R.L.; Sipe, M.A.

    1992-02-01

    Thirty-eight inactive liquid low-level radioactive waste tanks are currently managed by the Environmental Restoration Program of Oak Ridge National Laboratory. The contents of these tanks are to be characterized in preparation for future corrective actions and remediation activities as part of compliance with the pending Federal Facility Agreement for the Oak Ridge Reservation. Twenty-nine of these tanks were sampled and analyzed in 1989. Three of the tanks (TH-2, WC-1, and WC-15) were not accessible from the surface and thus were not sampled until 1990. This report presents the sampling and analytical results of that campaign. All three tanks in this report had negligible regulatory organic compounds in the samples that were collected. There were no US Environmental Protection Agency (EPA) Target Compound List (TCL) constituents for volatile organics detected in any of the aqueous samples. The only semivolatile organics detected were 2-chlorophenol (52 {mu}g/L) in tank TH-2 and dichloroethane (14--15 {mu}g/L) and diethyl either (15--17 {mu}g/L) in tank WC-15. A thin oil layer was discovered floating on top of the aqueous contents in tank WC-15. The analysis of the oil layer detected no volatile organics and showed only one EPA TCL constituent, di-n-butylphthalate, at 1900 {mu}g/L. Low levels of Resource Conservation and Recovery Act (RCRA) metals were observed in the samples from tank TH-2, but only the mercury level exceeded the RCRA limit. Samples from tank WC-1 had elevated levels of the RCRA metals barium, chromium, and lead. There were also finely suspended particles in one of the samples from tank WC-1, which was filtered and analyzed separately. This solid fines have levels of transuranium elements {sup 238}Pu and {sup 241}Am high enough to classified as transuranic waste.

  11. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers

    PubMed Central

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher

    2016-01-01

    Objectives This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. Methods This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical–demographic data were also collected. Results In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were ‘pain interferes with my exercise’ (33%) and ‘I have an injury/disability that stops me’ (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). Conclusions More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM. PMID:27547438

  12. Prolonged physical inactivity leads to a drop in toe skin temperature during local cold stress.

    PubMed

    Keramidas, Michail E; Kölegård, Roger; Eiken, Ola; Mekjavic, Igor B

    2014-03-01

    The purpose was to examine the effects of a prolonged period of recumbency on the toe temperature responses during cold-water foot immersion. Ten healthy males underwent 35 days of horizontal bed rest. The right foot of the subjects was assigned as the experimental (EXP) foot. To prevent bed rest-induced vascular deconditioning in the left control foot (CON), a sub-atmospheric vascular pressure countermeasure regimen was applied on the left lower leg for 4 × 10 min every second day. On the first (BR-1) and the last (BR-35) day of the bed rest, subjects performed two 30 min foot immersion tests in 8 °C water, one with the EXP foot and the other with the CON foot. The tests were conducted in counter-balanced order and separated by at least a 15 min interval. At BR-35, the average skin temperature of the EXP foot was lower than at BR-1 (-0.8 °C; P = 0.05), a drop that was especially pronounced in the big toe (-1.6 °C; P = 0.05). In the CON foot, the average skin temperature decreased by 0.6 °C in BR-35, albeit the reduction was not statistically significant (P = 0.16). Moreover, the pressure countermeasure regimen ameliorated immersion-induced thermal discomfort for the CON foot (P = 0.05). Present findings suggest that severe physical inactivity exaggerates the drop in toe skin temperature during local cold stress, and thus might constitute a potential risk factor for local cold injury. PMID:24552380

  13. Personalised Prescription of Scalable High Intensity Interval Training to Inactive Female Adults of Different Ages

    PubMed Central

    Mair, Jacqueline L.

    2016-01-01

    Stepping is a convenient form of scalable high-intensity interval training (HIIT) that may lead to health benefits. However, the accurate personalised prescription of stepping is hampered by a lack of evidence on optimal stepping cadences and step heights for various populations. This study examined the acute physiological responses to stepping exercise at various heights and cadences in young (n = 14) and middle-aged (n = 14) females in order to develop an equation that facilitates prescription of stepping at targeted intensities. Participants completed a step test protocol consisting of randomised three-minute bouts at different step cadences (80, 90, 100, 110 steps·min-1) and step heights (17, 25, 30, 34 cm). Aerobic demand and heart rate values were measured throughout. Resting metabolic rate was measured in order to develop female specific metabolic equivalents (METs) for stepping. Results revealed significant differences between age groups for METs and heart rate reserve, and within-group differences for METs, heart rate, and metabolic cost, at different step heights and cadences. At a given step height and cadence, middle-aged females were required to work at an intensity on average 1.9 ± 0.26 METs greater than the younger females. A prescriptive equation was developed to assess energy cost in METs using multilevel regression analysis with factors of step height, step cadence and age. Considering recent evidence supporting accumulated bouts of HIIT exercise for health benefits, this equation, which allows HIIT to be personally prescribed to inactive and sedentary women, has potential impact as a public health exercise prescription tool. PMID:26848956

  14. Sp3 proteins negatively regulate beta myosin heavy chain gene expression during skeletal muscle inactivity.

    PubMed

    Tsika, Gretchen; Ji, Juan; Tsika, Richard

    2004-12-01

    In adult skeletal muscle, beta myosin heavy chain (betaMyHC) gene expression is primarily restricted to slow type I fibers; however, its expression is down-regulated in response to muscle inactivity. Little is known about the signaling pathways and transcription factors that mediate this important functional response. This study demonstrates that increased binding of Sp3 to GC-rich elements in the betaMyHC promoter is a critical event in down-regulation of betaMyHC gene expression under non-weight-bearing conditions. Conversely, binding of Sp3 to these elements decreased while Sp1 binding increased with nuclear extracts from plantaris muscle exposed to mechanical overload, a stimulus that increases betaMyHC gene expression. In addition, these experiments revealed the existence of an Sp4-DNA binding complex when using adult skeletal muscle nuclear extract was used but not when nuclear extracts from cultured myotubes were used. Sp3 proteins are competitive inhibitors of Sp1-mediated betaMyHC reporter gene transactivation in both Drosophila SL-2 and mouse C2C12 myotubes. Sp4 is a weak activator of betaMyHC gene expression in SL-2 cells, which lack endogenous Sp1 activity, but does not activate betaMyHC gene expression in C2C12 myotubes, which have high levels of Sp1. These results suggest that competitive binding of Sp family proteins regulate betaMyHC gene transcription in response to altered neuromuscular activity. PMID:15572681

  15. Personalised Prescription of Scalable High Intensity Interval Training to Inactive Female Adults of Different Ages.

    PubMed

    Mair, Jacqueline L; Nevill, Alan M; De Vito, Giuseppe; Boreham, Colin A

    2016-01-01

    Stepping is a convenient form of scalable high-intensity interval training (HIIT) that may lead to health benefits. However, the accurate personalised prescription of stepping is hampered by a lack of evidence on optimal stepping cadences and step heights for various populations. This study examined the acute physiological responses to stepping exercise at various heights and cadences in young (n = 14) and middle-aged (n = 14) females in order to develop an equation that facilitates prescription of stepping at targeted intensities. Participants completed a step test protocol consisting of randomised three-minute bouts at different step cadences (80, 90, 100, 110 steps·min-1) and step heights (17, 25, 30, 34 cm). Aerobic demand and heart rate values were measured throughout. Resting metabolic rate was measured in order to develop female specific metabolic equivalents (METs) for stepping. Results revealed significant differences between age groups for METs and heart rate reserve, and within-group differences for METs, heart rate, and metabolic cost, at different step heights and cadences. At a given step height and cadence, middle-aged females were required to work at an intensity on average 1.9 ± 0.26 METs greater than the younger females. A prescriptive equation was developed to assess energy cost in METs using multilevel regression analysis with factors of step height, step cadence and age. Considering recent evidence supporting accumulated bouts of HIIT exercise for health benefits, this equation, which allows HIIT to be personally prescribed to inactive and sedentary women, has potential impact as a public health exercise prescription tool. PMID:26848956

  16. Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient

    PubMed Central

    Heyn, Holger; Vidal, Enrique; Sayols, Sergi; Sanchez-Mut, Jose V.; Moran, Sebastian; Medina, Ignacio; Sandoval, Juan; Simó-Riudalbas, Laia; Szczesna, Karolina; Huertas, Dori; Gatto, Sole; Matarazzo, Maria R.; Dopazo, Joaquin; Esteller, Manel

    2012-01-01

    The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable to analyze single loci were applied to determine epigenetic alterations in ICF patients. In the current study, we performed whole-genome bisulphite sequencing to assess alteration in DNA methylation at base pair resolution. Genome-wide we detected a decrease of methylation level of 42%, with the most profound changes occurring in inactive heterochromatic regions, satellite repeats and transposons. Interestingly, transcriptional active loci and ribosomal RNA repeats escaped global hypomethylation. Despite a genome-wide loss of DNA methylation the epigenetic landscape and crucial regulatory structures were conserved. Remarkably, we revealed a mislocated activity of mutant DNMT3B to H3K4me1 loci resulting in hypermethylation of active promoters. Functionally, we could associate alterations in promoter methylation with the ICF syndrome immunodeficient phenotype by detecting changes in genes related to the B-cell receptor mediated maturation pathway. PMID:22595875

  17. Aberrant Processing of Polyphenol Oxidase in a Variegated Grapevine Mutant 1

    PubMed Central

    Rathjen, Anne H.; Robinson, Simon P.

    1992-01-01

    Bruce's Sport is a mutant grapevine (Vitis vinifera L.) with green and white variegated fruit derived from the Sultana variety. The white regions of tissue have decreased polyphenol oxidase (PPO) activity resulting in a reduced capacity for browning. Active PPO from Sultana grapes was purified and had an apparent molecular weight of 40,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Western blots indicated that mature Sultana grapes contained a single 40-kilodalton PPO, and young Sultana berries also had small quantities of a 60-kilodalton protein. Bruce's Sport grapes had much less of the 40-kilodalton PPO and greater amounts of the 60-kilodalton band. Protease digestion of Bruce's Sport extracts decreased the proportion of the 60-kilodalton protein and increased the 40-kilodalton band. A cDNA clone of grape PPO was used to probe a northern blot of Sultana and Bruce's Sport RNA and hybridized to a 2.2-kilobase transcript in both grapevines. The level of PPO mRNA was high in the early stages of berry development but then declined. The results suggest that in grapevine the active 40-kilodalton form of PPO is synthesized as a precursor protein of at least 60 kilodaltons, and normal processing is interrupted in Bruce's Sport resulting in the accumulation of the 60-kilodalton inactive preform of PPO. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:16669082

  18. How deeply does your mutant sleep? Probing arousal to better understand sleep defects in Drosophila

    PubMed Central

    Faville, R.; Kottler, B.; Goodhill, G. J.; Shaw, P. J.; van Swinderen, B.

    2015-01-01

    The fruitfly, Drosophila melanogaster, has become a critical model system for investigating sleep functions. Most studies use duration of inactivity to measure sleep. However, a defining criterion for sleep is decreased behavioral responsiveness to stimuli. Here we introduce the Drosophila ARousal Tracking system (DART), an integrated platform for efficiently tracking and probing arousal levels in animals. This video-based platform delivers positional and locomotion data, behavioral responsiveness to stimuli, sleep intensity measures, and homeostatic regulation effects – all in one combined system. We show how insight into dynamically changing arousal thresholds is crucial for any sleep study in flies. We first find that arousal probing uncovers different sleep intensity profiles among related genetic background strains previously assumed to have equivalent sleep patterns. We then show how sleep duration and sleep intensity can be uncoupled, with distinct manipulations of dopamine function producing opposite effects on sleep duration but similar sleep intensity defects. We conclude by providing a multi-dimensional assessment of combined arousal and locomotion metrics in the mutant and background strains. Our approach opens the door for deeper insights into mechanisms of sleep regulation and provides a new method for investigating the role of different genetic manipulations in controlling sleep and arousal. PMID:25677943

  19. Partial budgeting assessment of the treatment of pyometra, follicular cysts and ovarian inactivity causing postpartum anoestrus in dairy cattle.

    PubMed

    el-Tahawy, Abd el-Gawad Salah; Fahmy, Mostafa Mohammed

    2011-02-01

    A total of 412 multiparous German Holstein cows were screened for postpartum pyometra, follicular cysts and ovarian inactivity to assess economic and productivity losses in relation to pharmaceutical expenditures. Our results show that cows treated for pyometra with prostaglandin f2 alpha (PGF2α) and oxytetracycline had significantly (P<0.05) greater total and net returns than untreated cows or those treated with PGF2α+cephapirin or PGF2α alone. Milk yields from untreated cows affected by follicular cysts were significantly (P<0.05) lower than the yields from cows treated with gonadotrophin-releasing hormone (GnRH)- and GnRH+PGF2α. In addition, the use of GnRH to treat cows with ovarian inactivity resulted in significantly (P<0.05) lower costs and greater total and net return values compared to untreated controls. PMID:20466393

  20. A Smartwatch-Based Assistance System for the Elderly Performing Fall Detection, Unusual Inactivity Recognition and Medication Reminding.

    PubMed

    Deutsch, Markus; Burgsteiner, Harald

    2016-01-01

    The growing number of elderly people in our society makes it increasingly important to help them live an independent and self-determined life up until a high age. A smartwatch-based assistance system should be implemented that is capable of automatically detecting emergencies and helping elderly people to adhere to their medical therapy. Using the acceleration data of a widely available smartwatch, we implemented fall detection and inactivity recognition based on a smartphone connected via Bluetooth. The resulting system is capable of performing fall detection, inactivity recognition, issuing medication reminders and alerting relatives upon manual activation. Though some challenges, like the dependence on a smartphone remain, the resulting system is a promising approach to help elderly people as well as their relatives to live independently and with a feeling of safety. PMID:27139412

  1. FTIR assay method for UV inactive drug carisoprodol and identification of degradants by RP-HPLC and ESI-MS.

    PubMed

    Acharya, Pratap Chandra; Vasi, Ruqaiya; Suares, Divya

    2016-09-01

    A new method of analysis has been developed for UV inactive drug carisoprodol using FTIR spectroscopy. These methods were validated for various parameters according to ICH guidelines. The proposed method has also been successfully applied for the determination of the drug concentration in a tablet formulation. The method proved to be accurate (mean percentage recovery between 95 and 105%), precise and reproducible (relative standard deviation<2%), while being simple, economical and less time consuming than other methods and can be used for routine estimation of carisoprodol in the pharmaceutical industry. The developed method also implicates its utility for other UV inactive substances. The stability of the drug under various stress conditions was studied and the drug was found to be particularly susceptible to alkaline hydrolysis. Degradation products of the alkaline hydrolysis were detected by RP-HPLC and tentatively identified by ESI-MS. PMID:27398631

  2. Correctors of mutant CFTR enhance subcortical cAMP-PKA signaling through modulating ezrin phosphorylation and cytoskeleton organization.

    PubMed

    Abbattiscianni, Anna C; Favia, Maria; Mancini, Maria T; Cardone, Rosa A; Guerra, Lorenzo; Monterisi, Stefania; Castellani, Stefano; Laselva, Onofrio; Di Sole, Francesca; Conese, Massimo; Zaccolo, Manuela; Casavola, Valeria

    2016-03-15

    The most common mutation of the cystic fibrosis transmembrane regulator (CFTR) gene, F508del, produces a misfolded protein resulting in its defective trafficking to the cell surface and an impaired chloride secretion. Pharmacological treatments partially rescue F508del CFTR activity either directly by interacting with the mutant protein and/or indirectly by altering the cellular protein homeostasis. Here, we show that the phosphorylation of ezrin together with its binding to phosphatidylinositol-4,5-bisphosphate (PIP2) tethers the F508del CFTR to the actin cytoskeleton, stabilizing it on the apical membrane and rescuing the sub-membrane compartmentalization of cAMP and activated PKA. Both the small molecules trimethylangelicin (TMA) and VX-809, which act as 'correctors' for F508del CFTR by rescuing F508del-CFTR-dependent chloride secretion, also restore the apical expression of phosphorylated ezrin and actin organization and increase cAMP and activated PKA submembrane compartmentalization in both primary and secondary cystic fibrosis airway cells. Latrunculin B treatment or expression of the inactive ezrin mutant T567A reverse the TMA and VX-809-induced effects highlighting the role of corrector-dependent ezrin activation and actin re-organization in creating the conditions to generate a sub-cortical cAMP pool of adequate amplitude to activate the F508del-CFTR-dependent chloride secretion. PMID:26823603

  3. Relation between anaerobic inactivation and oxygen tolerance in a large series of NiFe hydrogenase mutants.

    PubMed

    Abou Hamdan, Abbas; Liebgott, Pierre-Pol; Fourmond, Vincent; Gutiérrez-Sanz, Oscar; De Lacey, Antonio L; Infossi, Pascale; Rousset, Marc; Dementin, Sébastien; Léger, Christophe

    2012-12-01

    Nickel-containing hydrogenases, the biological catalysts of oxidation and production, reversibly inactivate under anaerobic, oxidizing conditions. We aim at understanding the mechanism of (in)activation and what determines its kinetics, because there is a correlation between fast reductive reactivation and oxygen tolerance, a property of some hydrogenases that is very desirable from the point of view of biotechnology. Direct electrochemistry is potentially very useful for learning about the redox-dependent conversions between active and inactive forms of hydrogenase, but the voltammetric signals are complex and often misread. Here we describe simple analytical models that we used to characterize and compare 16 mutants, obtained by substituting the position-74 valine of the -sensitive NiFe hydrogenase from Desulfovibrio fructosovorans. We observed that this substitution can accelerate reactivation up to 1,000-fold, depending on the polarity of the position 74 amino acid side chain. In terms of kinetics of anaerobic (in)activation and oxygen tolerance, the valine-to-histidine mutation has the most spectacular effect: The V74H mutant compares favorably with the -tolerant hydrogenase from Aquifex aeolicus, which we use here as a benchmark. PMID:23169623

  4. Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia.

    PubMed

    Bokori-Brown, Monika; Hall, Charlotte A; Vance, Charlotte; Fernandes da Costa, Sérgio P; Savva, Christos G; Naylor, Claire E; Cole, Ambrose R; Basak, Ajit K; Moss, David S; Titball, Richard W

    2014-05-13

    Epsilon toxin (Etx) is a β-pore-forming toxin produced by Clostridium perfringens toxinotypes B and D and plays a key role in the pathogenesis of enterotoxemia, a severe, often fatal disease of ruminants that causes significant economic losses to the farming industry worldwide. This study aimed to determine the potential of a site-directed mutant of Etx (Y30A-Y196A) to be exploited as a recombinant vaccine against enterotoxemia. Replacement of Y30 and Y196 with alanine generated a stable variant of Etx with significantly reduced cell binding and cytotoxic activities in MDCK.2 cells relative to wild type toxin (>430-fold increase in CT50) and Y30A-Y196A was inactive in mice after intraperitoneal administration of trypsin activated toxin at 1000× the expected LD50 dose of trypsin activated wild type toxin. Moreover, polyclonal antibody raised in rabbits against Y30A-Y196A provided protection against wild type toxin in an in vitro neutralisation assay. These data suggest that Y30A-Y196A mutant could form the basis of an improved recombinant vaccine against enterotoxemia. PMID:24709588

  5. Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

    PubMed Central

    Bokori-Brown, Monika; Hall, Charlotte A.; Vance, Charlotte; Fernandes da Costa, Sérgio P.; Savva, Christos G.; Naylor, Claire E.; Cole, Ambrose R.; Basak, Ajit K.; Moss, David S.; Titball, Richard W.

    2014-01-01

    Epsilon toxin (Etx) is a β-pore-forming toxin produced by Clostridium perfringens toxinotypes B and D and plays a key role in the pathogenesis of enterotoxemia, a severe, often fatal disease of ruminants that causes significant economic losses to the farming industry worldwide. This study aimed to determine the potential of a site-directed mutant of Etx (Y30A-Y196A) to be exploited as a recombinant vaccine against enterotoxemia. Replacement of Y30 and Y196 with alanine generated a stable variant of Etx with significantly reduced cell binding and cytotoxic activities in MDCK.2 cells relative to wild type toxin (>430-fold increase in CT50) and Y30A-Y196A was inactive in mice after intraperitoneal administration of trypsin activated toxin at 1000× the expected LD50 dose of trypsin activated wild type toxin. Moreover, polyclonal antibody raised in rabbits against Y30A-Y196A provided protection against wild type toxin in an in vitro neutralisation assay. These data suggest that Y30A-Y196A mutant could form the basis of an improved recombinant vaccine against enterotoxemia. PMID:24709588

  6. Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer.

    PubMed

    Choe, Cholho; Yang, Ling; Lv, Zhanao; Mo, Wanling; Chen, Zhuqi; Li, Guangxin; Yin, Guochuan

    2015-05-21

    Redox-inactive metal ions can modulate the reactivity of redox-active metal ions in a variety of biological and chemical oxidations. Many synthetic models have been developed to help address the elusive roles of these redox-inactive metal ions. Using a non-heme manganese(II) complex as the model, the influence of redox-inactive metal ions as a Lewis acid on its catalytic efficiency in oxygen atom transfer was investigated. In the absence of redox-inactive metal ions, the manganese(II) catalyst is very sluggish, for example, in cyclooctene epoxidation, providing only 9.9% conversion with 4.1% yield of epoxide. However, addition of 2 equiv. of Al(3+) to the manganese(II) catalyst sharply improves the epoxidation, providing up to 97.8% conversion with 91.4% yield of epoxide. EPR studies of the manganese(II) catalyst in the presence of an oxidant reveal a 16-line hyperfine structure centered at g = 2.0, clearly indicating the formation of a mixed valent di-μ-oxo-bridged diamond core, Mn(III)-(μ-O)2-Mn(IV). The presence of a Lewis acid like Al(3+) causes the dissociation of this diamond Mn(III)-(μ-O)2-Mn(IV) core to form monomeric manganese(iv) species which is responsible for improved epoxidation efficiency. This promotional effect has also been observed in other manganese complexes bearing various non-heme ligands. The findings presented here have provided a promising strategy to explore the catalytic reactivity of some di-μ-oxo-bridged complexes by adding non-redox metal ions to in situ dissociate those dimeric cores and may also provide clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate. PMID:25904197

  7. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado

    SciTech Connect

    Not Available

    1992-02-01

    This appendix assesses the present conditions and data gathered about the two inactive uranium mill tailings sites near Rifle, Colorado, and the designated disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

  8. Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging.

    PubMed

    Gifford, Aliya; Towse, Theodore F; Walker, Ronald C; Avison, Malcolm J; Welch, E Brian

    2016-07-01

    Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own. PMID:27166284

  9. US state- and county-level social capital in relation to obesity and physical inactivity: a multilevel, multivariable analysis.

    PubMed

    Kim, Daniel; Subramanian, S V; Gortmaker, Steven L; Kawachi, Ichiro

    2006-08-01

    Although social capital has been linked to a variety of health outcomes, its association with obesity has yet to be elucidated. This study explored the relations between social capital measured at the US state and county levels and individual obesity and leisure-time physical inactivity. Individual-level data were drawn from the 2001 Behavioral Risk Factor Surveillance System survey, while data from other surveys and administrative sources were used to construct contextual measures. Two state-level social capital scales were derived from 10 indicators and two county-level scales from five indicators. In 2-level analyses of over 167,000 adults nested within 48 states plus the District of Columbia, residence in a state above the median on one or both state social capital scales (vs. neither scale) was associated with lower relative odds of obesity and physical inactivity, controlling for individual-level covariables and state-level estimates of mean household income, the Gini coefficient, and the percentage of Black residents. In 3-level analyses, the adjusted odds ratio (OR) for physical inactivity associated with residence in a county above the median on one or both county social capital scales was significantly below 1, while the association with obesity was not significant. Significantly weaker inverse ORs for the relations between state- and county-level social capital and obesity were observed among American Indians/Alaska Natives compared to Whites. Meanwhile, little support was found for mediation by social capital of the associations of urban sprawl and income inequality with obesity or physical inactivity. Overall, this study provides some evidence for the promotion of social capital as a potential strategy for addressing the burgeoning obesity epidemic. PMID:16644081

  10. Hazard ranking system evaluation of CERCLA inactive waste sites at Hanford: Volume 3: Unplanned-release sites (HISS data base)

    SciTech Connect

    Jette, S.J.; Lamar, D.A.; McLaughlin, T.J.; Sherwood, D.R.; Van Houten, N.C.; Stenner, R.D; Cramer, K.H.; Higley, K.A.

    1988-10-01

    The purpose of this report is to formally document the assessment activities at the US Department of Energy (DOE) Hanford Site. These activities were carried out pursuant to the DOE orders that address the Comprehensive Environmental Response, and Liability Act (CERCLA) Program for the cleanup of inactive waste sites. The DOE orders incorporate the US Environmental Protection Agency methodology, which is based on the Superfund Amendments and Reauthorization Act of 1986. This methodology includes:PA/SI, remedial investigation/feasibility study, record of decision, design and implementation or remedial action, operation and monitoring, and verification monitoring. Volume 1 of this report discusses the CERCLA inactive waste-site evaluation process, assumptions, and results of the Hazard Ranking System methodology employed. Volume 2 presents the data on the individual CERCLA engineered-facility sites at Hanford, as contained in the Hanford Inactive Site Surveillance (HISS) Data Base. Volume 3 presents the data on the individual CERCLA unplanned-release sites at Hanford, as contained in the HISS Data Base. 13 figs.

  11. Modification of the ATP inhibitory site of the Ascaris suum phosphofructokinase results in the stabilization of an inactive T state

    SciTech Connect

    Rao, G.S.J.; Cook, P.F.; Harris, B.G. )

    1991-10-15

    Treatment of the Ascaris suum phosphofructokinase (PFK) with 2{prime},3{prime}-dialdehyde ATP (oATP) results in an enzyme form that is inactive. The conformational integrity of the active site, however, is preserved, suggesting that oATP modification locks the PFK into an inactive T state that cannot be activated. A rapid, irreversible first-order inactivation of the PFK is observed in the presence of oATP. The rate of inactivation is saturable and gives a K{sub oATP} of 1.07 {plus minus} 0.27 mM. Complete protection against inactivation is afforded by high concentrations of ATP. This desensitized enzyme incorporates only 0.2-0.3 mol of ({sup 3}H)oATP/subunit, suggesting that in te native enzyme inactivation perhaps results from the modification of the ATP inhibitory site rather than the catalytic site. Modification of an active-site thiol by 4,4{prime}-dithiodipyridine is prevented yb ATP before and after oATP treatment. Finally, gel filtration HPLC studies show that the oATP-modified enzyme retains its tetrameric state and neither the tryptophan fluorescence nor the circular dichroic spectra of the modified enzyme are affected by fructose 2,6-bisphosphate, suggesting that the enzyme is locked into a tetrameric inactive T state.

  12. The diseasome of physical inactivity--and the role of myokines in muscle--fat cross talk.

    PubMed

    Pedersen, Bente K

    2009-12-01

    Type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, dementia and depression constitute a cluster of diseases, which defines 'a diseasome of physical inactivity'. Both physical inactivity and abdominal adiposity, reflecting accumulation of visceral fat mass, are associated with the occurrence of the diseases within the diseasome. Physical inactivity appears to be an independent and strong risk factor for accumulation of visceral fat, which again is a source of systemic inflammation. Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration and tumour growth. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the anti-inflammatory effect of regular exercise, which can be mediated via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise. The finding that muscles produce and release myokines provides a conceptual basis to understand the mechanisms whereby exercise influences metabolism and exerts anti-inflammatory effects. According to our theory, contracting skeletal muscles release myokines, which work in a hormone-like fashion, exerting specific endocrine effects on visceral fat. Other myokines work locally within the muscle via paracrine mechanisms, exerting their effects on signalling pathways involved in fat oxidation. PMID:19752112

  13. Hazard ranking system evaluation of CERCLA inactive waste sites at Hanford: Volume 2: Engineered-facility sites (HISS data base)

    SciTech Connect

    Jette, S.J.; Lamar, D.A.; McLaughlin, T.J.; Sherwood, D.R.; Van Houten, N.C.; Stenner, R.D.; Cramer, K.H.; Higley, K.A.

    1988-10-01

    The purpose of this report is to formally document the assessment activities at the US Department of Energy (DOE) Hanford Site. These activities were carried out pursuant to the DOE orders that address the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Program for the cleanup of inactive waste sites. The DOE orders incorporate the US Environmental Protection Agency methodology, which is based on the Superfund Amendments and Reauthorization Act of 1986. This methodology includes: PA/SI, remedial investigation/feasibility study, record of decision, design and implementation of remedial action, operation and monitoring, and verification monitoring. Volume 1 of this report discusses the CERCLA inactive waste-site evaluation process, assumptions, and results of the Hazard Ranking System methodology employed. Volume 2 presents the data on the individual CERCLA engineered-facility sites at Hanford, as contained in the Hanford Inactive Site Surveillance (HISS) Data Base. Volume 3 presents the data on the individual CERCLA unplanned-release sites at Hanford, as contained in the HISS Data Base. 13 refs.

  14. Active and inactive enhancers co-operate to exert localized and long-range control of gene regulation

    PubMed Central

    Proudhon, Charlotte; Snetkova, Valentina; Raviram, Ramya; Lobry, Camille; Badri, Sana; Jiang, Tingting; Hao, Bingtao; Trimarchi, Thomas; Kluger, Yuval; Aifantis, Iannis; Bonneau, Richard; Skok, Jane A

    2016-01-01

    V(D)J recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR) loci in a lineage and stage specific manner. Unexpectedly we find that both active and inactive AgR enhancers co-operate to disseminate their effects in a localized and long-range manner. Here we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. We further establish that in T cells long-range contact and co-operation between the inactive Igk enhancer, MiEκ and the active Tcrb enhancer, Eβ, alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage and stage specific control. PMID:27239026

  15. What causes low magnetization at basalt-hosted hydrothermal sites? Insights from inactive site Krasnov (MAR 16°38'N)

    NASA Astrophysics Data System (ADS)

    Szitkar, Florent; Dyment, Jérôme; Choi, Yujin; Fouquet, Yves

    2014-04-01

    magnetic surveys acquired near the seafloor show that active basalt-hosted hydrothermal sites are associated with zones of lower magnetization. This observation may reflect the thermal demagnetization of a hot hydrothermal zone, the alteration of basalt affected by hydrothermal circulation, and/or the presence of thick, nonmagnetic hydrothermal deposits. In order to discriminate among these inferences, we acquired vector magnetic data 50 m above inactive hydrothermal site Krasnov using the Remotely Operated Vehicle (ROV) Victor. This deep hydrothermal site, located 7 km east of the Mid-Atlantic Ridge (MAR) axis at 16°38'N, is dissected by major normal faults and shows no evidence of recent hydrothermal activity. It is therefore a perfect target for investigating the magnetic signature of an inactive basalt-hosted hydrothermal site. Krasnov exhibits a strong negative magnetic anomaly, which implies that the lower magnetization observed at basalt-hosted hydrothermal sites is not a transient effect associated with hydrothermal activity, but remains after activity ceases. Thermal demagnetization plays only a secondary role, if any, in the observed magnetic low. Forward models suggest that both the nonmagnetic hydrothermal deposits and an altered zone of demagnetized basalt are required to account for the observed magnetic low. The permanence of this magnetic signature makes it a useful tool to explore midocean ridges and detect inactive hydrothermal sites.

  16. Crystal structural basis for Rv0315, an immunostimulatory antigen and inactive beta-1,3-glucanase of Mycobacterium tuberculosis

    PubMed Central

    Dong, Wanyu; Huang, Junhua; Li, Yanan; Tan, Yubei; Shen, Zhou; Song, Yunfeng; Wang, Dang; Xiao, Shaobo; Chen, Huanchun; Fu, Zhen F.; Peng, Guiqing

    2015-01-01

    Mycobacterium tuberculosis (Mtb) remains a leading cause of morbidity and mortality worldwide, as two billion people are latently infected with Mtb. To address Mtb drug resistance and the limitations of current vaccines, the characteristics of candidate Mtb vaccines need to be explored. Here, we report the three-dimensional structure of Rv0315 at 1.70 Å resolution, a novel immunostimulatory antigen of Mtb, and demonstrate that Rv0315 is an inactive β-1,3-glucanase of the glycoside hydrolase 16 (GH16) family. Our study further elaborates the molecular basis for the lack of glucan recognition by Rv0315. Rv0315 has a large open groove, and this particular topology cannot bind oligosaccharide chains in solution, thus explaining the lack of detectable hydrolytic activity towards its substrate. Additionally, we identified Glu-176, a conserved catalytic residue in GH16 endo-β-1,3-glucanases, as essential for Rv0315 to induce immunological responses. These results indicate that Rv0315 likely diverged from a broad-specificity ancestral GH16 glucanase, and this inactive member of the GH16 family offers new insights into the GH16 glucanase. Together, our findings suggest that an inactive β-1,3-glucanase in Mtb drives T-helper 1 (Th1) immune responses, which may help develop more effective vaccines against Mtb infection. PMID:26469317

  17. Mutant p53 in cell adhesion and motility.

    PubMed

    Yeudall, W Andrew; Wrighton, Katharine H; Deb, Sumitra

    2013-01-01

    Pro-oncogenic properties of mutant p53 were investigated with the aid of migration assays, adhesion assays, and soft agar growth assays using cells stably expressing gain-of-function p53 mutants. To determine cell migration, "wound-healing" (scratch) assays and haptotactic (chamber) assays were used. H1299 cells expressing mutant p53 were found to migrate more rapidly than cells transfected with empty vector alone. Results from both types of migration assay were broadly similar. Migratory ability differed for different p53 mutants, suggesting allele-specific effects. Cells expressing p53 mutants also showed enhanced adhesion to extracellular matrix compare to controls. Furthermore, stable transfection of mutant p53-H179L into NIH3T3 fibroblasts was sufficient to allow anchorage-independent growth in soft agar. PMID:23150443

  18. Characterization of Pseudomonas aeruginosa mutants with altered piliation.

    PubMed Central

    Johnson, K; Lory, S

    1987-01-01

    The pilus-specific Pseudomonas aeruginosa bacteriophage P04 was used to select spontaneous mutants of strain PAK which have altered piliation. The largest class of phage-resistant mutants synthesized the pilin polypeptide, but did not assemble pili. These mutants are likely to contain mutations in genes required for pilus assembly and not mutations in the pilin structural gene, as they could not be complemented by a normal copy of the pilin gene. In addition, two alterations in pilin gene transcription were found among the mutants--hyperpiliated mutants which overproduce pilin mRNA, and a mutant with temperature-sensitive pilin gene transcription. We also present a model for the regulation of pilin gene transcription by a feedback mechanism sensitive to the relative rates of pilus assembly and disassembly. Images PMID:2445731

  19. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    PubMed Central

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed. PMID:26618142

  20. Optimized cell transplantation using adult rag2 mutant zebrafish

    PubMed Central

    Tang, Qin; Abdelfattah, Nouran S.; Blackburn, Jessica S.; Moore, John C.; Martinez, Sarah A.; Moore, Finola E.; Lobbardi, Riadh; Tenente, Inês M.; Ignatius, Myron S.; Berman, Jason N.; Liwski, Robert S.; Houvras, Yariv; Langenau, David M.

    2014-01-01

    Cell transplantation into adult zebrafish has lagged behind mouse due to the lack of immune compromised models. Here, we have created homozygous rag2E450fs mutant zebrafish that have reduced numbers of functional T and B cells but are viable and fecund. Mutant fish engraft zebrafish muscle, blood stem cells, and cancers. rag2E450fs mutant zebrafish are the first immune compromised zebrafish model that permits robust, long-term engraftment of multiple tissues and cancer. PMID:25042784

  1. Isolation and characterization of Klebsiella pneumoniae unencapsulated mutants

    SciTech Connect

    Benedi, V.J.; Ciurana, B.; Tomas, J.M.

    1989-01-01

    Klebsiella pneumoniae mutants were obtained after UV irradiation and negative selection with anticapsular serum. Unencapsulation, rather than expression of a structurally altered capsule, was found in the mutants. The mutant strains showed no alterations in their outer membrane proteins and lipopolysaccharide, and a great similarity with the wild type in the properties tested (serum resistance, antimicrobial sensitivity, and lipopolysaccharide-specific bacteriophage sensitivity), with the exception of a higher cell surface hydrophobicity and resistance to bacteriophage FC3-9.

  2. Genomic analysis of cichlid fish 'natural mutants'.

    PubMed

    Kuraku, Shigehiro; Meyer, Axel

    2008-12-01

    In the lakes of East Africa, cichlid fishes have formed adaptive radiations that are each composed of hundreds of endemic, morphologically stunningly diverse, but genetically extremely similar species. In the past 20 years, it became clear that their extreme phenotypic diversity arose within very short time spans, and that phenotypically radically different species are exceptionally similar genetically; hence, they could be considered to be 'natural mutants'. Many species can be hybridized and, therefore, provide a unique opportunity to study the genetic underpinnings of phenotypic diversification. Comparative large-scale genomic analyses are beginning to unravel the patterns and processes that led to the formation of the cichlid species flocks. Cichlids are an emerging evolutionary genomic model system for fundamental questions on the origin of phenotypic diversity. PMID:19095433

  3. Computational approaches for predicting mutant protein stability.

    PubMed

    Kulshreshtha, Shweta; Chaudhary, Vigi; Goswami, Girish K; Mathur, Nidhi

    2016-05-01

    Mutations in the protein affect not only the structure of protein, but also its function and stability. Prediction of mutant protein stability with accuracy is desired for uncovering the molecular aspects of diseases and design of novel proteins. Many advanced computational approaches have been developed over the years, to predict the stability and function of a mutated protein. These approaches based on structure, sequence features and combined features (both structure and sequence features) provide reasonably accurate estimation of the impact of amino acid substitution on stability and function of protein. Recently, consensus tools have been developed by incorporating many tools together, which provide single window results for comparison purpose. In this review, a useful guide for the selection of tools that can be employed in predicting mutated proteins' stability and disease causing capability is provided. PMID:27160393

  4. Sphingolipid synthesis deficiency in a mutant of Bacteroides levii

    SciTech Connect

    Brumleve, B.; Lev, M.

    1986-05-01

    Bacteroides levii, an anaerobic bacterium, synthesizes two sphingolipids; the sphingomyelin analogue, ceramide phosphorylethanolamine (CPE), and also ceramide phosphorylglycerol (CPG). The first enzyme in the sphingolipid pathway, 3-ketodihydro-sphingosine (3KDS) synthase, has been partially purified previously. To study subsequent steps in the pathways, mutants defective in sphingolipid synthesis were derived by ethyl methanesulfonate and nitrosoguanidine mutagenesis. Extracts of the mutant, 1075BB, show synthase activity although the cells do not synthesize CPE or CPG. The mutant differs from the wild type in that: (1) synthase activity was much diminished in the mutant, (2) sphingolipid synthesis does not occur in the mutant as evidenced by the absence of spots at sites where CPE and CPG migrate following two-dimensional thin layer chromatography, (3) incorporation of uniformly-labelled (/sup 14/C)serine carbon or (/sup 14/C)3KDS into sphingolipids was not observed in the mutant, (4) following incubation with (/sup 14/C)3KDS, radioactivity corresponding to dihydrosphingosine (DHS) and ceramide were observed in the mutant; no (/sup 14/C)DHS was detected in the wild type, and (5) enhanced incorporation of (/sup 14/C)serine carbon into two lipids not containing phosphorus was found in the mutant. The authors conclude, therefore, that this mutant, 1075BB, has a metabolic block at the terminal biosynthetic steps of sphingolipid synthesis.

  5. [Pigment composition and photosynthetic activity of pea chlorophyll mutants].

    PubMed

    Ladygin, V G

    2003-01-01

    Pea chlorophyll mutants chlorotica 2004 and 2014 have been studied. The mutants differ from the initial form (pea cultivar Torsdag) in stem and leaf color (light green in the mutant 2004 and yellow-green in the mutant 2014), relative chlorophyll content (approximately 80 and 50%, respectively), and the composition of carotenoids: the mutant 2004 contains a significantly smaller amount of carotene but accumulates more lutein and violaxanthine; in the mutant 2014, the contents of all carotenoids are decreased proportionally to the decrease in chlorophyll content. It is shown that the rates of CO2 assimilation and oxygen production in the mutant chlorotica 2004 and 2014 plants are reduced. The quantum efficiency of photosynthesis in the mutants is 29-30% lower than in the control plants; in their hybrids, however, it is 1.5-2 higher. It is proposed that both the greater role of dark respiration in gas exchange and the reduced photosynthetic activity in chlorotica mutants are responsible for the decreased phytomass increment in these plants. On the basis of these results, the conclusion is drawn that the mutations chlorotica 2004 and 2014 affect the genes controlling the formation and functioning of various components of the photosynthetic apparatus. PMID:12942751

  6. Growth and development of maize that contains mutant tubulin genes

    SciTech Connect

    Susan M. Wick

    2004-07-23

    Mutant maize plants containing a Mu transposon disrupting one of the five beta tubulin genes of interest were followed for several generations and hybridized with each other to produce plants containing disruptions in both copies of a single gene or disruption of more than one tubulin gene. Seedlings of some of these plants were grown under chilling conditions for a few weeks. After DOE funding ended, plants have been assessed to see whether mutant are more or less tolerant to chilling. Other mutant plants will be assessed for their male and female fertility relative to non-mutant siblings or other close relatives.

  7. Identification of mutant monoclonal antibodies with increased antigen binding.

    PubMed Central

    Pollock, R R; French, D L; Gefter, M L; Scharff, M D

    1988-01-01

    Sib selection and an ELISA have been used to isolate hybridoma subclones producing mutant antibodies that bind antigen better than the parental monoclonal antibody. Such mutants arise spontaneously in culture at frequencies of 2.5-5 X 10(-5). The sequences of the heavy and light chain variable regions of the mutant antibodies are identical to that of the parent and the Ka values of the mutants and the parent are the same. The increase in binding is associated with abnormalities of the constant region polypeptide and probably reflect changes in avidity of these antibodies. Images PMID:3267219

  8. Analysis of canthaxanthin and related pigments from Gordonia jacobaea mutants.

    PubMed

    de Miguel, T; Sieiro, C; Poza, M; Villa, T G

    2001-03-01

    A collection of 43 mutant strains of the bacterium Gordonia jacobaea was obtained by means of ethyl methanesulfonate treatment, and the strains were selected for their different pigmentation with respect to the wild-type strain. None of the mutants showed auxotrophy. They all showed good genetic stability and a growth rate similar to that of the parental strain. Canthaxanthin and other carotenoids from these mutants were extracted with acetone and ethanol and separated by high-performance liquid chromatography (HPLC). These HPLC analyses, together with spectrophotometric detection at 480 nm, revealed variations in the pigment contents of the different mutant strains. PMID:11312835

  9. Enhanced star formation rates in AGN hosts with respect to inactive galaxies from PEP-Herschel observations

    NASA Astrophysics Data System (ADS)

    Santini, P.; Rosario, D. J.; Shao, L.; Lutz, D.; Maiolino, R.; Alexander, D. M.; Altieri, B.; Andreani, P.; Aussel, H.; Bauer, F. E.; Berta, S.; Bongiovanni, A.; Brandt, W. N.; Brusa, M.; Cepa, J.; Cimatti, A.; Daddi, E.; Elbaz, D.; Fontana, A.; Förster Schreiber, N. M.; Genzel, R.; Grazian, A.; Le Floc'h, E.; Magnelli, B.; Mainieri, V.; Nordon, R.; Pérez Garcia, A. M.; Poglitsch, A.; Popesso, P.; Pozzi, F.; Riguccini, L.; Rodighiero, G.; Salvato, M.; Sanchez-Portal, M.; Sturm, E.; Tacconi, L. J.; Valtchanov, I.; Wuyts, S.

    2012-04-01

    We compare the average star formation (SF) activity in X-ray selected AGN hosts with a mass-matched control sample of inactive galaxies, including both star forming and quiescent sources, in the 0.5 < z < 2.5 redshift range. Recent observations carried out by PACS, the 60-210 μm photometric camera on board the Herschel Space Observatory, in GOODS-S, GOODS-N and COSMOS allow us to obtain an unbiased estimate of the far-IR luminosity, and hence of the SF properties, of the two samples. Accurate AGN host stellar mass estimates are obtained by decomposing their total emission into the stellar and the nuclear components. We report evidence of a higher average SF activity in AGN hosts with respect to the control sample of inactive galaxies. The level of SF enhancement is modest (~0.26 dex at ~3σ confidence level) at low X-ray luminosities (LX ≲ 1043.5 erg s-1) and more pronounced (0.56 dex at > 10σ confidence level) in the hosts of luminous AGNs. However, when comparing to star forming galaxies only, AGN hosts are found broadly consistent with the locus of their "main sequence". We investigate the relative far-IR luminosity distributions of active and inactive galaxies, and find a higher fraction of PACS detected, hence normal and highly star forming systems among AGN hosts. Although different interpretations are possible, we explain our findings as a consequence of a twofold AGN growth path: faint AGNs evolve through secular processes, with instantaneous AGNaccretion not tightly linked to the current total SF in the host galaxy, while the luminous AGNs co-evolve with their hosts through periods of enhanced AGN activity and star formation, possibly through major mergers. While an increased SF activity with respect to inactive galaxies of similar mass is expected in the latter, we interpret the modest SF offsets measured in low-LX AGN hosts as either a) generated by non-synchronous accretion and SF histories in a merger scenario or b) due to possible connections

  10. Controlling access time to a high-fat diet during the inactive period protects against obesity in mice.

    PubMed

    Haraguchi, Atsushi; Aoki, Natsumi; Ohtsu, Teiji; Ikeda, Yuko; Tahara, Yu; Shibata, Shigenobu

    2014-10-01

    Free feeding (FF) with a high fat diet (HFD) causes excessive body weight gain, whereas restricted feeding (RF) with a HFD attenuates body weight gain. The effects of timing of feeding with a HFD (day vs. night) and feeding duration on energy homeostasis have not yet been investigated. In this study, we fed mice a HFD or a normal diet (ND) twice a day, during their active and inactive periods, on a schedule. The amount of food was regulated by feeding duration (2, 4 or 8 h). First, we investigated the effects of 4-h RF during active-inactive periods (ND-ND, HFD-HFD, ND-HFD or HFD-ND). Among all the 4-h RF groups, mice consumed almost the same amount of calories as those in the FF[ND] group, even those fed a HFD. Body weight and visceral fat in these three groups were lower than that in the FF[HFD] group. Second, we investigated the effects of RF duration. Body weight and visceral fat were higher in the 8-h groups than in the 4-h groups. Body weight and visceral fat were higher in the 2-h groups than in the 4-h groups even though the 2-h groups had less food. Third, we investigated the effects of eating a HFD during the inactive period, when RF duration was extended (2, 6 or 12 h). Mice were fed with a HFD during the inactive period for 2 h and fed with a ND during the active period for 2, 6 or 12 h. Body weight and visceral fat in these mice were comparable to those in the FF[ND] mice. The results of our first set of experiments suggest that 4-h RF was an adequate feeding duration to control the effect of a HFD on obesity. The results of our second set of experiments suggest 2-h RF (such as speed-eating) and 8-h RF, representative of eating disorders, are unhealthy feeding patterns related to obesity. The results of our third set of experiments suggest that eating a HFD for a short period during the night does not affect body weight and visceral fat. Taken together, these results indicate that consideration to feeding with a HFD during the inactive period and

  11. Spinal TNF is necessary for inactivity-induced phrenic motor facilitation.

    PubMed

    Broytman, Oleg; Baertsch, Nathan A; Baker-Herman, Tracy L

    2013-11-15

    A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF), a 'rebound' increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long-lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor-α (TNFα) is necessary for iPMF via an aPKC-dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P < 0.05) was apparent, indicating long-lasting iPMF. Pretreatment with recombinant human soluble TNF receptor 1 (sTNFR1) in the intrathecal space at the level of the phrenic motor nucleus prior to neural apnoea blocked long-lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long-lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα-induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ-pseudosubstrate inhibitory peptide (PKCζ-PS) 35 min following intrathecal TNFα arrested TNFα-induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC-dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα-dependent increase in spinal aPKC activity. PMID:23878370

  12. Selective Retention of an Inactive Allele of the DKK2 Tumor Suppressor Gene in Hepatocellular Carcinoma

    PubMed Central

    Lin, Yung-Feng; Li, Ling-Hui; Lin, Chih-Hung; Tsou, Mei-Hua; Chuang, Ming-Tai Kiffer; Wu, Keh-Ming; Liao, Tsai-Lien; Li, Jian-Chiuan; Wang, Wei-Jie; Tomita, Angela; Tomita, Beverly; Huang, Shiu-Feng; Tsai, Shih-Feng

    2016-01-01

    In an effort to identify the functional alleles associated with hepatocellular carcinoma (HCC), we investigated 152 genes found in the 4q21-25 region that exhibited loss of heterozygosity (LOH). A total of 2,293 pairs of primers were designed for 1,449 exonic and upstream promoter regions to amplify and sequence 76.8–114 Mb on human chromosome 4. Based on the results from analyzing 12 HCC patients and 12 healthy human controls, we discovered 1,574 sequence variations. Among the 99 variants associated with HCC (p < 0.05), four are from the Dickkopf 2 (DKK2) gene: three in the promoter region (g.-967A>T, g.-923C>A, and g.-441T>G) and one in the 5’UTR (c.550T>C). To verify the results, we expanded the subject cohort to 47 HCC cases and 88 healthy controls for conducting haplotype analysis. Eight haplotypes were detected in the non-tumor liver tissue samples, but one major haplotype (TAGC) was found in the tumor tissue samples. Using a reporter assay, this HCC-associated allele registered the lowest level of promoter activity among all the tested haplotype sequences. Retention of this allele in LOH was associated with reduced DKK2 transcription in the HCC tumor tissues. In HuH-7 cells, DKK2 functioned in the Wnt/β-catenin signaling pathway, as an antagonist of Wnt3a, in a dose-dependent manner that inhibited Wnt3a-induced cell proliferation. Taken together, the genotyping and functional findings are consistent with the hypothesis that DKK2 is a tumor suppressor; by selectively retaining a transcriptionally inactive DKK2 allele, the reduction of DKK2 function results in unchecked Wnt/β-catenin signaling, contributing to HCC oncogenesis. Thus our study reveals a new mechanism through which a tumor suppressor gene in a LOH region loses its function by allelic selection. PMID:27203079

  13. Physical Inactivity Is Associated with Moderate-Severe Obstructive Sleep Apnea

    PubMed Central

    Simpson, Laila; McArdle, Nigel; Eastwood, Peter R.; Ward, Kim L.; Cooper, Matthew N.; Wilson, Annette C.; Hillman, David R.; Palmer, Lyle J.; Mukherjee, Sutapa

    2015-01-01

    Study Objectives: To investigate whether low levels of physical activity were associated with an increased occurrence of obstructive sleep apnea (OSA), OSA-related symptoms, and cardiometabolic risk. Methods: A case-control study design was used. OSA cases were patients referred to a sleep clinic for suspected OSA (n = 2,340). Controls comprised participants from the Busselton community (n = 1,931). Exercise and occupational activity were derived from questionnaire data. Associations were modelled using logistic and linear regression and adjusted for confounders. Results: In comparison with moderate exercise, the high, low, and nil exercise groups had an odds ratio (OR) for moderate-severe OSA of 0.6 (95% CI 0.5–0.8), 1.6 (95% CI 1.2–2.0), and 2.7 (95% CI 1.9–3.7), respectively. Relative to men in heavy activity occupations, men in medium, light and sedentary occupations had an OR for moderate-severe OSA of 1.7 (95% CI 1.1–2.5), 2.1 (95% CI 1.4–3.2), and 1.8 (95% CI 1.2–2.8), respectively. Relative to women in medium activity occupations, women in light and sedentary occupations had an OR for moderate-severe OSA of 4.2 (95% CI 2.6–7.2) and 3.5 (2.0–6.0). OSA patients who adequately exercised had lower: levels of doctor-diagnosed depression (p = 0.047); symptoms of fatigue (p < 0.0001); systolic (p = 0.015) and diastolic blood pressure (p = 0.015); and C-reactive protein (CRP) (p = 0.003). Conclusions: Low levels of physical activity were associated with moderate-severe OSA. Exercise in individuals with OSA is associated with lower levels of depression, fatigue, blood pressure and CRP. Citation: Simpson L, McArdle N, Eastwood PR, Ward KL, Cooper MN, Wilson AC, Hillman DR, Palmer LJ, Mukherjee S. Physical inactivity is associated with moderate-severe obstructive sleep apnea. J Clin Sleep Med 2015;11(10):1091–1099. PMID:26285117

  14. Spinal TNFα is necessary for inactivity-induced phrenic motor facilitation

    PubMed Central

    Broytman, Oleg; Baertsch, Nathan A; Baker-Herman, Tracy L

    2013-01-01

    A prolonged reduction in central neural respiratory activity elicits a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF), a ‘rebound’ increase in phrenic burst amplitude apparent once respiratory neural activity is restored. iPMF requires atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize an early transient increase in phrenic burst amplitude and to form long-lasting iPMF following reduced respiratory neural activity. Upstream signal(s) leading to spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour necrosis factor-α (TNFα) is necessary for iPMF via an aPKC-dependent mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea; upon resumption of respiratory neural activity, a prolonged increase in phrenic burst amplitude (42 ± 9% baseline; P < 0.05) was apparent, indicating long-lasting iPMF. Pretreatment with recombinant human soluble TNF receptor 1 (sTNFR1) in the intrathecal space at the level of the phrenic motor nucleus prior to neural apnoea blocked long-lasting iPMF (2 ± 8% baseline; P > 0.05). Intrathecal TNFα without neural apnoea was sufficient to elicit long-lasting phrenic motor facilitation (pMF; 62 ± 7% baseline; P < 0.05). Similar to iPMF, TNFα-induced pMF required spinal aPKC activity, as intrathecal delivery of a ζ-pseudosubstrate inhibitory peptide (PKCζ-PS) 35 min following intrathecal TNFα arrested TNFα-induced pMF (28 ± 8% baseline; P < 0.05). These data demonstrate that: (1) spinal TNFα is necessary for iPMF; and (2) spinal TNFα is sufficient to elicit pMF via a similar aPKC-dependent mechanism. These data are consistent with the hypothesis that reduced respiratory neural activity elicits iPMF via a TNFα-dependent increase in spinal aPKC activity. PMID:23878370

  15. Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.; Haddad, F.

    2001-01-01

    The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of

  16. Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes congenital I- transport defect.

    PubMed

    Reed-Tsur, Mia D; De la Vieja, Antonio; Ginter, Christopher S; Carrasco, Nancy

    2008-06-01

    I(-) is actively transported into thyrocytes via the Na+/I(-) symporter (NIS), a key glycoprotein located on the basolateral plasma membrane. The cDNA encoding rat NIS was identified in our laboratory, where an extensive structure/function characterization of NIS is being conducted. Several NIS mutants have been identified as causes of congenital I(-) transport defect (ITD), including V59E NIS. ITD is characterized by low thyroid I(-) uptake, low saliva/plasma I(-) ratio, hypothyroidism, and goiter and may cause mental retardation if untreated. Studies of other ITD-causing NIS mutants have revealed valuable information regarding NIS structure/function. V59E NIS was reported to exhibit as much as 30% of the activity of wild-type NIS. However, this observation was at variance with the patients' phenotype of total lack of activity. We have thoroughly characterized V59E NIS and studied several amino acid substitutions at position 59. We demonstrated that, in contrast to the previous report, V59E NIS is inactive, although it is properly targeted to the plasma membrane. Glu and all other charged amino acids or Pro at position 59 also yielded nonfunctional NIS proteins. However, I(-) uptake was rescued to different degrees by the other substitutions. Although the Km values for Na+ and I(-) were not altered in these active mutants, we found that the structural requirement for NIS function at position 59 is a neutral, helix-promoting amino acid. This result suggests that the region that contains V59 may be involved in intramembrane helix-helix interactions during the transport cycle without being in direct contact with the substrates. PMID:18339708

  17. Unfavorable electrostatic and steric interactions in DNA polymerase β E295K mutant interfere with the enzyme’s pathway

    PubMed Central

    Li, Yunlang; Gridley, Chelsea L.; Jaeger, Joachim; Sweasy, Joann B.; Schlick, Tamar

    2012-01-01

    Mutations in DNA polymerase β (pol β) have been associated with approximately 30% of human tumors. The E295K mutation of pol β has been linked to gastric carcinoma via interference with base excision repair. To interpret the different behavior of E295K compared to wild-type pol β in atomic and energetic detail, we resolve a binary crystal complex of E295K at 2.5 Å and apply transition path sampling (TPS) to delineate the closing pathway of the E295K pol β mutant. Conformational changes are important components in the enzymatic pathway that lead to and ready the enzyme for the chemical reaction. Our analyses show that the closing pathway of E295K mutant differs from the wild-type pol β in terms of the individual transition states along the pathway, associated energies, and the active site conformation in the final closed form of the mutant. In particular, the closed state of E295K has a more distorted active site than the active site in the wild-type pol β. In addition, the total energy barrier in the conformational closing pathway is 65 ± 11 kJ/mol, much higher than that estimated for both correct (e.g., G:C) and incorrect (e.g., G:A) wild-type pol β systems (42 ± 8 kJ/mol and 45 ± 7 kJ/mol, respectively). In particular, the rotation of Arg258 is the rate-limiting step in the conformational pathway of E295K due to unfavorable electrostatic and steric interactions. The distorted active site in the closed relative to open state and the high energy barrier in the conformational pathway may explain in part why the E295K mutant is observed to be inactive. Interestingly, however, following the closing of the thumb but prior to the rotation of Arg258, the E295K mutant complex has a similar energy level compared to the wild-type pol β. This suggests that the E295K mutant may associate with DNA with similar affinity, but it may be hampered in continuing the process of chemistry. Supporting experimental data come from the observation that the catalytic activity

  18. Mutant prevention concentration and mutant selection window for 10 antimicrobial agents against Rhodococcus equi.

    PubMed

    Berghaus, Londa J; Giguère, Steeve; Guldbech, Kristen

    2013-10-25

    The objectives of this study were to determine the mutant prevention concentration (MPC), time above the MPC and mutant selection window for 10 antimicrobial agents against Rhodococcus equi and to determine if the combination of a macrolide with rifampin would decrease emergence of resistant mutants. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline) were selected based on in vitro activity and frequency of use in foals or people infected with R. equi. Each antimicrobial agent or combination of agents was evaluated against four virulent strains of R. equi. MPC were determined using an agar plate assay. Pharmacodynamic parameters were calculated using published plasma and pulmonary pharmacokinetic variables. There was a significant (P<0.001) effect of the type of antimicrobial agent on the MPC. The MPC of clarithromycin (1.0 μg/ml) was significantly lower and the MPC of rifampin and amikacin (512 and 384 μg/ml, respectively) were significantly higher than that of all other antimicrobial agents tested. Combining erythromycin, clarithromycin, or azithromycin with rifampin resulted in a significant (P≤0.005) decrease in MPC and MPC/MIC ratio. When MIC and MPC were combined with pharmacokinetic variables, only gentamicin and vancomycin were predicted to achieve plasma concentrations above the MPC for any given periods of time. Only clarithromycin and the combination clarithromycin-rifampin were predicted to achieve concentrations in bronchoalveolar cells and pulmonary epithelial lining fluid above the MPC for the entire dosing interval. In conclusion, the combination of a macrolide with rifampin considerably decreases the emergence of resistant mutants of R. equi. PMID:23915992

  19. Yeast meiotic mutants proficient for the induction of ectopic recombination.

    PubMed Central

    Engebrecht, J; Masse, S; Davis, L; Rose, K; Kessel, T

    1998-01-01

    A screen was designed to identify Saccharomyces cerevisiae mutants that were defective in meiosis yet proficient for meiotic ectopic recombination in the return-to-growth protocol. Seven mutants alleles were isolated; two are important for chromosome synapsis (RED1, MEK1) and five function independently of recombination (SPO14, GSG1, SPOT8/MUM2, 3, 4). Similar to the spoT8-1 mutant, mum2 deletion strains do not undergo premeiotic DNA synthesis, arrest prior to the first meiotic division and fail to sporulate. Surprisingly, although DNA replication does not occur, mum2 mutants are induced for high levels of ectopic recombination. gsg1 diploids are reduced in their ability to complete premeiotic DNA synthesis and the meiotic divisions, and a small percentage of cells produce spores. mum3 mutants sporulate poorly and the spores produced are inviable. Finally, mum4-1 mutants produce inviable spores. The meiotic/sporulation defects of gsg1, mum2, and mum3 are not relieved by spo11 or spo13 mutations, indicating that the mutant defects are not dependent on the initiation of recombination or completion of both meiotic divisions. In contrast, the spore inviability of the mum4-1 mutant is rescued by the spo13 mutation. The mum4-1 spo13 mutant undergoes a single, predominantly equational division, suggesting that MUM4 functions at or prior to the first meiotic division. Although recombination is variably affected in the gsg1 and mum mutants, we hypothesize that these mutants define genes important for aspects of meiosis not directly related to recombination. PMID:9504908

  20. A mouse model for a partially inactive obesity-associated human MC3R variant

    PubMed Central

    Lee, Bonggi; Koo, Jashin; Yun Jun, Joo; Gavrilova, Oksana; Lee, Yongjun; Seo, Arnold Y.; Taylor-Douglas, Dezmond C.; Adler-Wailes, Diane C.; Chen, Faye; Gardner, Ryan; Koutzoumis, Dimitri; Sherafat Kazemzadeh, Roya; Roberson, Robin B.; Yanovski, Jack A.

    2016-01-01

    We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3RhWT/hWT) and double-mutant (C17A+G241A) human (MC3RhDM/hDM) MC3R, that MC3RhDM/hDM have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3RhWT/hWT. MC3RhDM/hDM mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3RhDM/hDM mice and MC3RhDM/hDM human subjects. MC3RhDM/hDM bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3RhWT/hWT MSCs. MC3RhDM/hDM impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. PMID:26818770

  1. Structure-biological function relationship extended to mitotic arrest-deficient 2-like protein Mad2 native and mutants-new opportunity for genetic disorder control.

    PubMed

    Avram, Speranta; Milac, Adina; Mernea, Maria; Mihailescu, Dan; Putz, Mihai V; Buiu, Catalin

    2014-01-01

    Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding to specific partners (cell-division cycle protein 20 (Cdc20) or Mad1) were targets of previous pharmacogenomics studies. Here, Mad2 binding to Cdc20 and the interconversion rate from open to closed Mad2 were predicted and the molecular features with a critical contribution to these processes were determined by extending the quantitative structure-activity relationship (QSAR) method to large-size proteins such as Mad2. QSAR models were built based on available published data on 23 Mad2 mutants inducing CIN-related functional changes. The most relevant descriptors identified for predicting Mad2 native and mutants action mechanism and their involvement in genetic disorders are the steric (van der Waals area and solvent accessible area and their subdivided) and energetic van der Waals energy descriptors. The reliability of our QSAR models is indicated by significant values of statistical coefficients: Cross-validated correlation q2 (0.53-0.65) and fitted correlation r2 (0.82-0.90). Moreover, based on established QSAR equations, we rationally design and analyze nine de novo Mad2 mutants as possible promoters of CIN. PMID:25411801

  2. Comment and response document on the final remedial action plan and site design for stabilization of the inactive Uranium Mill Tailings Site at Lakeview, Oregon

    SciTech Connect

    Not Available

    1991-10-01

    This report contains comments provided by the Oregon Department of Energy and responses to these comments on the final remedial action plan for the inactive uranium mill tailings site at Lakeview, Oregon.

  3. A Mutant Hunt Using the C-Fern (Ceratopteris Richardii)

    ERIC Educational Resources Information Center

    Calie, Patrick J.

    2005-01-01

    A modification of the popular C-Fern system, the tropical fern Ceratopteris richardii is developed in which students plate out a genetically mixed set of fern spores and then select for specific mutants. This exercise can provide students with an experience in plant mutant selection and can be used as a platform to expose students to a diverse…

  4. Structurally altered capsular polysaccharides produced by mutant bacteria

    NASA Technical Reports Server (NTRS)

    Kern, Roger G. (Inventor); Petersen, Gene R. (Inventor); Richards, Gil F. (Inventor)

    1995-01-01

    Structurally altered capsular polysaccharides are produced by mutant bacteria. These polysaccharides are isolated by selecting a wild type bacterial strain and a phage producing degradative enzymes that have substrate specificity for the capsular polysaccharides produced by the wild type bacteria. Phage-resistant mutants producing capsular polysaccharides are selected and the structurally altered capsular polysaccharide is isolated therefrom.

  5. Isolation of Temperature-Sensitive Mutants of L-Cells*

    PubMed Central

    Thompson, L. H.; Mankovitz, R.; Baker, R. M.; Till, J. E.; Siminovitch, L.; Whitmore, G. F.

    1970-01-01

    Procedures are described for the isolation of conditional lethal mutants of mouse L-60T cells. The mutant lines were temperature sensitive by the following criteria: (a) colony-forming ability, (b) growth in suspension culture, and (c) rate of uptake of tritiated-thymidine. Images PMID:5271170

  6. Mutant strain of C. acetobutylicum and process for making butanol

    DOEpatents

    Jain, Mahendra K.; Beacom, Daniel; Datta, Rathin

    1993-01-01

    A biologically pure asporogenic mutant of Clostridium acetobutylicum is produced by growing sporogenic C. acetobutylicum ATCC 4259 and treating the parent strain with ethane methane sulfonate. The mutant which as been designated C. acetobutylicum ATCC 55025 is useful in an improved ABE fermentation process, and produces high concentrations of butanol and total solvents.

  7. Histological and Molecular Characterization of Grape Early Ripening Bud Mutant

    PubMed Central

    Yu, Yi-He; Xi, Fei-Fei; Shi, Yan-Yan; Zhang, Guo-Hai

    2016-01-01

    An early ripening bud mutant was analyzed based on the histological, SSR, and methylation-sensitive amplified polymorphism (MSAP) analysis and a layer-specific approach was used to investigate the differentiation between the bud mutant and its parent. The results showed that the thickness of leaf spongy tissue of mutant (MT) is larger than that of wild type (WT) and the differences are significant. The mean size of cell layer L2 was increased in the mutant and the difference is significant. The genetic background of bud mutant revealed by SSR analysis is highly uniform to its parent; just the variations from VVS2 SSR marker were detected in MT. The total methylation ratio of MT is lower than that of the corresponding WT. The outside methylation ratio in MT is much less than that in WT; the average inner methylation ratio in MT is larger than that in WT. The early ripening bud mutant has certain proportion demethylation in cell layer L2. All the results suggested that cell layer L2 of the early ripening bud mutant has changed from the WT. This study provided the basis for a better understanding of the characteristic features of the early ripening bud mutant in grape. PMID:27610363

  8. Isolation of Mutants of the Nitrogen-Fixing Actinomycete Frankia

    PubMed Central

    Kakoi, Kentaro; Yamaura, Masatoshi; Kamiharai, Toshihito; Tamari, Daiki; Abe, Mikiko; Uchiumi, Toshiki; Kucho, Ken-Ichi

    2014-01-01

    Frankia is a nitrogen (N)-fixing multicellular actinomycete which establishes root-nodule symbiosis with actinorhizal plants. Several aspects of Frankia N fixation and symbiosis are distinct, but genes involved in the specific features are largely unknown because of the lack of an efficient mutant screening method. In this study, we isolated mutants of Frankia sp. strain CcI3 using hyphae fragments mutagenized by chemical mutagens. Firstly, we isolated uracil auxotrophs as gain-of-function mutants resistant to 5-fluoroorotic acid (5-FOA). We obtained seven 5-FOA resistant mutants, all of which required uracil for growth. Five strains carried a frame shift mutation in orotidine-5′-phosphate decarboxylase gene and two carried an amino acid substitution in the orotate phosphoribosyltransferase gene. Secondly, we isolated mutants showing loss-of-function phenotypes. Mutagenized hyphae were fragmented by ultrasound and allowed to multiply at their tips. Hyphae were fragmented again and short fragments were enriched by filtration through 5 μm pores filters. Next-generation and Sanger sequencing revealed that colonies formed from the short hyphae fragments consisted of cells with an identical genotype. From the mutagenized colony population, we isolated three pigmentation mutants and a mutant with reduced N-fixation activity. These results indicate that our procedure is useful for the isolation of loss-of-function mutants using hyphae of Frankia. PMID:24389412

  9. Sorghum Brown Midrib Mutants, Tools to Improve Biomass for Biofuels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To improve sorghum for cellulosic bioenergy uses, brown midrib mutants are being investigated for their ability to increase the conversion efficiency of biomass. brown midrib 6 and 12 (bmr6 and 12) mutants affect monolignol biosynthesis resulting in reduced lignin content and altered lignin composi...

  10. Gravitropism in roots of intermediate-starch mutants of Arabidopsis

    NASA Technical Reports Server (NTRS)

    Kiss, J. Z.; Wright, J. B.; Caspar, T.

    1996-01-01

    Gravitropism was studied in roots of wild type (WT) Arabidopsis thaliana (L.) Heynh. (strain Wassilewskija) and three starch-deficient mutants that were generated by T-DNA insertional mutagenesis. One of these mutants was starchless while the other two were intermediate mutants, which had 51% and 60%, respectively, of the WT amount of starch as determined by light and electron microscopy. The four parameters used to assay gravitropism were: orientation during vertical growth, time course of curvature, induction, and intermittent stimulation experiments. WT roots were much more responsive to gravity than were roots of the starchless mutant, and the intermediate starch mutants exhibited an intermediate graviresponse. Our data suggest that lowered starch content in the mutants primarily affects gravitropism rather than differential growth because both phototropic curvature and growth rates were approximately equal among all four genotypes. Since responses of intermediate-starch mutants were closer to the WT response than to the starchless mutant, it appears that 51-60% of the WT level of starch is near the threshold amount needed for full gravitropic sensitivity. While other interpretations are possible, the data are consistent with the starch statolith hypothesis for gravity perception in that the degree of graviresponsiveness is proportional to the total mass of plastids per cell.

  11. Mutant maize variety containing the glt1-1 allele

    DOEpatents

    Nelson, O.E.; Pan, D.

    1994-07-19

    A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating. 2 figs.

  12. Mutant maize variety containing the glt1-1 allele

    DOEpatents

    Nelson, Oliver E.; Pan, David

    1994-01-01

    A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating.

  13. Isolation of mutants of the nitrogen-fixing actinomycete Frankia.

    PubMed

    Kakoi, Kentaro; Yamaura, Masatoshi; Kamiharai, Toshihito; Tamari, Daiki; Abe, Mikiko; Uchiumi, Toshiki; Kucho, Ken-Ichi

    2014-01-01

    Frankia is a nitrogen (N)-fixing multicellular actinomycete which establishes root-nodule symbiosis with actinorhizal plants. Several aspects of Frankia N fixation and symbiosis are distinct, but genes involved in the specific features are largely unknown because of the lack of an efficient mutant screening method. In this study, we isolated mutants of Frankia sp. strain CcI3 using hyphae fragments mutagenized by chemical mutagens. Firstly, we isolated uracil auxotrophs as gain-of-function mutants resistant to 5-fluoroorotic acid (5-FOA). We obtained seven 5-FOA resistant mutants, all of which required uracil for growth. Five strains carried a frame shift mutation in orotidine-5'-phosphate decarboxylase gene and two carried an amino acid substitution in the orotate phosphoribosyltransferase gene. Secondly, we isolated mutants showing loss-of-function phenotypes. Mutagenized hyphae were fragmented by ultrasound and allowed to multiply at their tips. Hyphae were fragmented again and short fragments were enriched by filtration through 5 μm pores filters. Next-generation and Sanger sequencing revealed that colonies formed from the short hyphae fragments consisted of cells with an identical genotype. From the mutagenized colony population, we isolated three pigmentation mutants and a mutant with reduced N-fixation activity. These results indicate that our procedure is useful for the isolation of loss-of-function mutants using hyphae of Frankia. PMID:24389412

  14. Histological and Molecular Characterization of Grape Early Ripening Bud Mutant.

    PubMed

    Guo, Da-Long; Yu, Yi-He; Xi, Fei-Fei; Shi, Yan-Yan; Zhang, Guo-Hai

    2016-01-01

    An early ripening bud mutant was analyzed based on the histological, SSR, and methylation-sensitive amplified polymorphism (MSAP) analysis and a layer-specific approach was used to investigate the differentiation between the bud mutant and its parent. The results showed that the thickness of leaf spongy tissue of mutant (MT) is larger than that of wild type (WT) and the differences are significant. The mean size of cell layer L2 was increased in the mutant and the difference is significant. The genetic background of bud mutant revealed by SSR analysis is highly uniform to its parent; just the variations from VVS2 SSR marker were detected in MT. The total methylation ratio of MT is lower than that of the corresponding WT. The outside methylation ratio in MT is much less than that in WT; the average inner methylation ratio in MT is larger than that in WT. The early ripening bud mutant has certain proportion demethylation in cell layer L2. All the results suggested that cell layer L2 of the early ripening bud mutant has changed from the WT. This study provided the basis for a better understanding of the characteristic features of the early ripening bud mutant in grape. PMID:27610363

  15. Elucidation of the Photorhabdus temperata Genome and Generation of a Transposon Mutant Library To Identify Motility Mutants Altered in Pathogenesis

    PubMed Central

    Hurst, Sheldon; Rowedder, Holli; Michaels, Brandye; Bullock, Hannah; Jackobeck, Ryan; Abebe-Akele, Feseha; Durakovic, Umjia; Gately, Jon; Janicki, Erik

    2015-01-01

    ABSTRACT The entomopathogenic nematode Heterorhabditis bacteriophora forms a specific mutualistic association with its bacterial partner Photorhabdus temperata. The microbial symbiont is required for nematode growth and development, and symbiont recognition is strain specific. The aim of this study was to sequence the genome of P. temperata and identify genes that plays a role in the pathogenesis of the Photorhabdus-Heterorhabditis symbiosis. A draft genome sequence of P. temperata strain NC19 was generated. The 5.2-Mb genome was organized into 17 scaffolds and contained 4,808 coding sequences (CDS). A genetic approach was also pursued to identify mutants with altered motility. A bank of 10,000 P. temperata transposon mutants was generated and screened for altered motility patterns. Five classes of motility mutants were identified: (i) nonmotile mutants, (ii) mutants with defective or aberrant swimming motility, (iii) mutant swimmers that do not require NaCl or KCl, (iv) hyperswimmer mutants that swim at an accelerated rate, and (v) hyperswarmer mutants that are able to swarm on the surface of 1.25% agar. The transposon insertion sites for these mutants were identified and used to investigate other physiological properties, including insect pathogenesis. The motility-defective mutant P13-7 had an insertion in the RNase II gene and showed reduced virulence and production of extracellular factors. Genetic complementation of this mutant restored wild-type activity. These results demonstrate a role for RNA turnover in insect pathogenesis and other physiological functions. IMPORTANCE The relationship between Photorhabdus and entomopathogenic nematode Heterorhabditis represents a well-known mutualistic system that has potential as a biological control agent. The elucidation of the genome of the bacterial partner and role that RNase II plays in its life cycle has provided a greater understanding of Photorhabdus as both an insect pathogen and a nematode symbiont. PMID

  16. Bacillus sphaericus asporogenous mutants: morphology, protein pattern and larvicidal activity.

    PubMed

    Charles, J F; Kalfon, A; Bourgouin, C; de Barjac, H

    1988-01-01

    Asporogenous mutants from Bacillus sphaericus strains 2297 and 1593-4, blocked at different stages of the sporulation process, were isolated. Two mutants (2297 Aspo30A and 2297 Aspo34) which were blocked early in sporulation did not possess any crystalline inclusions and were poorly toxic to Culex pipiens mosquito larvae. Other mutants (2297 Aspo115, 2297 Aspo24 and 1593-4 Aspo12) which were blocked at later stages synthesized crystal-like inclusions next to the forespores, and were highly toxic to mosquito larvae. Electrophoretic protein analysis of alkali extracts from mutants and wild type strains confirmed the absence of toxic crystal-related proteins in early-blocked mutants and their presence in later ones. Western blots with antisera directed against the crystal proteins confirmed those observations. PMID:3408593

  17. Viable deletion mutants in the simian virus 40 early region.

    PubMed Central

    Feunteun, J; Kress, M; Gardes, M; Monier, R

    1978-01-01

    For the purpose of isolating hr-t-like mutants of simian virus 40, we have constructed variants that have lost the unique site for the restriction enzyme Taq I at 0.565. Five mutants have been isolated and characterized by restriction enzyme analysis. All of them produce a normal size T antigen. Four produce a t antigen reduced in size as well as in amount; the fifth one does not seem to make any t antigen at all. The ability of these mutants to transform mouse cells in vitro, as tested by anchorage dependence, is clearly altered; however, the defect is only partial. In the same test, the mutants can complement a tsA mutant for transformation and therefore define a second complementation group in the simian virus 40 early region. Images PMID:212752

  18. Huntington's disease cerebrospinal fluid seeds aggregation of mutant huntingtin

    PubMed Central

    Tan, Z; Dai, W; van Erp, T G M; Overman, J; Demuro, A; Digman, M A; Hatami, A; Albay, R; Sontag, E M; Potkin, K T; Ling, S; Macciardi, F; Bunney, W E; Long, J D; Paulsen, J S; Ringman, J M; Parker, I; Glabe, C; Thompson, L M; Chiu, W; Potkin, S G

    2015-01-01

    Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. This seeding assay distinguishes HD subjects from healthy and non-HD dementia controls without overlap (blinded samples). Ultimately, this seeding property in HD patient CSF may form the basis of a molecular biomarker assay to monitor HD and evaluate therapies that target mHTT. PMID:26100538

  19. Architectural phenotypes in the transparent testa mutants of Arabidopsis thaliana

    PubMed Central

    Buer, Charles S.; Djordjevic, Michael A.

    2009-01-01

    Flavonoids are low molecular weight secondary plant metabolites with a myriad of functions. As flavonoids affect auxin transport (an important growth-controlling hormone) and are biologically active in eukaryotes, flavonoid mutants were expected to have undescribed architectural phenotypes. The Arabidopsis thaliana transparent testa (tt) mutants are compromised in the enzymatic steps or transcriptional regulators affecting flavonoid synthesis. tt mutant seedlings were grown on hard-slanted agar (a stress condition), under varying light conditions, and in soil to examine the resulting growth patterns. These tt mutants revealed a wide variety of architectural phenotypes in root and aerial tissues. Mutants with increased inflorescences, siliques, and lateral root density or reduced stature are traits that could affect plant yield or performance under certain environmental conditions. The regulatory genes affected in architectural traits may provide useful molecular targets for examination in other plants. PMID:19129166

  20. Overcoming the risk of inaction from emissions uncertainty in smallholder agriculture

    NASA Astrophysics Data System (ADS)

    Berry, N. J.; Ryan, C. M.

    2013-03-01

    The potential for improving productivity and increasing the resilience of smallholder agriculture, while also contributing to climate change mitigation, has recently received considerable political attention (Beddington et al 2012). Financial support for improving smallholder agriculture could come from performance-based funding including sale of carbon credits or certified commodities, payments for ecosystem services, and nationally appropriate mitigation action (NAMA) budgets, as well as more traditional sources of development and environment finance. Monitoring the greenhouse gas fluxes associated with changes to agricultural practice is needed for performance-based mitigation funding, and efforts are underway to develop tools to quantify mitigation achieved and assess trade-offs and synergies between mitigation and other livelihood and environmental priorities (Olander 2012). High levels of small scale variability in carbon stocks and emissions in smallholder agricultural systems (Ziegler et al 2012) mean that data intensive approaches are needed for precise and unbiased mitigation monitoring. The cost of implementing such monitoring programmes is likely to be high, and this introduces the risk that projects will not be developed in areas where there is the greatest need for agricultural improvements, which are likely to correspond with areas where existing data or research infrastructure are lacking. When improvements to livelihoods and food security are expected as co-benefits of performance-based mitigation finance, the risk of inaction is borne by the rural poor as well as the global climate. In situ measurement of carbon accumulation in smallholders' soils are not usually feasible because of the costs associated with sampling in a heterogeneous landscape, although technological advances could improve the situation (Milori et al 2012). Alternatives to in situ measurement are to estimate greenhouse gas fluxes by extrapolating information from existing

  1. A mouse model for a partially inactive obesity-associated human MC3R variant.

    PubMed

    Lee, Bonggi; Koo, Jashin; Yun Jun, Joo; Gavrilova, Oksana; Lee, Yongjun; Seo, Arnold Y; Taylor-Douglas, Dezmond C; Adler-Wailes, Diane C; Chen, Faye; Gardner, Ryan; Koutzoumis, Dimitri; Sherafat Kazemzadeh, Roya; Roberson, Robin B; Yanovski, Jack A

    2016-01-01

    We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3R(hWT/hWT). MC3R(hDM/hDM) mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3R(hWT/hWT) MSCs. MC3R(hDM/hDM) impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. PMID:26818770

  2. Expression of enzymatically inactive wasp venom phospholipase A1 in Pichia pastoris.

    PubMed

    Borodina, Irina; Jensen, Bettina M; Wagner, Tim; Hachem, Maher A; Søndergaard, Ib; Poulsen, Lars K

    2011-01-01

    Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification.Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect on growth of the yeast cells. To overcome the problem we introduced three different point mutations at the critical points of the active site, where serine137, aspartate165 or histidine229 were replaced by alanine (S137A, D165A and H229A). All the three mutated forms could be expressed in P. pastoris. The H229A mutant did not have any detectable phospholipase A1 activity and was secreted at the level of several mg/L in shake flask culture. The protein was purified by nickel-affinity chromatography and its identity was confirmed by MALDI-TOF mass spectrometry. The protein could bind IgE antibodies from wasp venom allergic patients and could inhibit the binding of wasp venom to IgE antibodies specific for phospholipase A1 as shown by Enzyme Allergo-Sorbent Test (EAST). Moreover, the recombinant protein was allergenic in a biological assay as demonstrated by its capability to induce histamine release of wasp venom-sensitive basophils.The recombinant phospholipase A1 presents a good candidate for wasp venom immunotherapy. PMID:21731687

  3. Expression of Enzymatically Inactive Wasp Venom Phospholipase A1 in Pichia pastoris

    PubMed Central

    Borodina, Irina; Jensen, Bettina M.; Wagner, Tim; Hachem, Maher A.; Søndergaard, Ib; Poulsen, Lars K.

    2011-01-01

    Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification. Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect on growth of the yeast cells. To overcome the problem we introduced three different point mutations at the critical points of the active site, where serine137, aspartate165 or histidine229 were replaced by alanine (S137A, D165A and H229A). All the three mutated forms could be expressed in P. pastoris. The H229A mutant did not have any detectable phospholipase A1 activity and was secreted at the level of several mg/L in shake flask culture. The protein was purified by nickel-affinity chromatography and its identity was confirmed by MALDI-TOF mass spectrometry. The protein could bind IgE antibodies from wasp venom allergic patients and could inhibit the binding of wasp venom to IgE antibodies specific for phospholipase A1 as shown by Enzyme Allergo-Sorbent Test (EAST). Moreover, the recombinant protein was allergenic in a biological assay as demonstrated by its capability to induce histamine release of wasp venom-sensitive basophils. The recombinant phospholipase A1 presents a good candidate for wasp venom immunotherapy. PMID:21731687

  4. Thermal stability of active/inactive nanocomposite anodes based on Cu2Sb in lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Allcorn, Eric; Kim, Sang-Ok; Manthiram, Arumugam

    2015-12-01

    Various active/inactive nanocomposites of Cu2Sb-Al2O3@C, Cu2Sb-TiC, and Cu2Sb-TiC@C have been synthesized by high energy mechanical milling and investigated by differential scanning calorimetry (DSC) to determine the lithiated phase stability and heat generation arising from these electrodes. The milling process reduces the Li3Sb phase stability, relative to the un-milled samples, to below ∼200 °C. However, the incorporation of the reinforcing, inactive phases Al2O3, TiC, and carbon black offer a slight improvement. DSC curves also show that the low-temperature heat generation in the SEI-layer reaction range is not noticeably altered by either the milling process or the addition of the inactive phases. A strong exothermic peak is observed at ∼200 °C for the 0% state of charge electrodes of Cu2Sb-Al2O3@C and Cu2Sb-TiC@C that was caused by the incorporation of carbon black into the composite. This peak was not present in the electrodes of milled Cu2Sb or Cu2Sb-TiC, suggesting that efforts to extend the cycle life of alloy anodes should avoid carbon black due to its destabilizing effects on delithiated electrodes. Fourier Transform infrared spectroscopy analysis indicates that the reaction arising from the incorporation of carbon black is tied to a low-temperature breakdown of the lithium salt LiPF6.

  5. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men.

    PubMed

    Zembron-Lacny, A; Dziubek, W; Rynkiewicz, M; Morawin, B; Woźniewski, M

    2016-06-20

    Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF) and its relationship to oxidative damage and conventional cardiovascular disease (CVD) biomarkers, such as atherogenic index, C-reactive protein (hsCRP) and oxidized LDL (oxLDL), in active and inactive men. Seventeen elderly males (61-80 years) and 17 young males (20-24 years) participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001). In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL), hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men. PMID:27332774

  6. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    PubMed Central

    Zembron-Lacny, A.; Dziubek, W.; Rynkiewicz, M.; Morawin, B.; Woźniewski, M.

    2016-01-01

    Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF) and its relationship to oxidative damage and conventional cardiovascular disease (CVD) biomarkers, such as atherogenic index, C-reactive protein (hsCRP) and oxidized LDL (oxLDL), in active and inactive men. Seventeen elderly males (61-80 years) and 17 young males (20-24 years) participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001). In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL), hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men. PMID:27332774

  7. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

    PubMed Central

    Li, Ming-Hui; Xie, Yao; Zhang, Lu; Lu, Yao; Shen, Ge; Wu, Shu-Ling; Chang, Min; Mu, Cai-Qin; Hu, Lei-Ping; Hua, Wen-Hao; Song, Shu-Jing; Zhang, Shu-Feng; Cheng, Jun; Xu, Dao-Zhen

    2016-01-01

    AIM: To examine the association between interferon (IFN) therapy and loss of hepatitis B surface antigen (HBsAg) in inactive HBsAg carriers. METHODS: This was a retrospective cohort study in inactive HBsAg carriers, who were treatment-naive, with a serum HBsAg level < 100 IU/mL and an undetectable hepatitis B virus (HBV) DNA level (< 100 IU/mL). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBsAg, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen (65.0%) of 20 treated patients achieved HBsAg loss, 12 of whom achieved HBsAg seroconversion. Mean HBsAg level in treated patients decreased to 6.69 ± 13.04 IU/mL after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/mL. Serum HBV DNA level remained undetectable (< 100 IU/mL) in all treated patients during the study. HBsAg level of the control group decreased from 25.72 ± 25.58 IU/mL at baseline to 17.11 ± 21.62 IU/mL at week 96 (P = 0.108). In the control group, no patient experienced HBsAg loss/seroconversion, and two (5.0%) developed HBV reactivation. CONCLUSION: IFN treatment results in HBsAg loss and seroconversion in a considerable proportion of inactive HBsAg carriers with low HBsAg concentrations. PMID:27239256

  8. Effect of Physical Inactivity on the Oxidation of Saturated and Monounsaturated Dietary Fatty Acids: Results of a Randomized Trial

    PubMed Central

    Bergouignan, Audrey; Schoeller, Dale A; Normand, Sylvie; Gauquelin-Koch, Guillemette; Laville, Martine; Shriver, Timothy; Desage, Michel; Maho, Yvon Le; Ohshima, Hiroshi; Gharib, Claude; Blanc, Stéphane

    2006-01-01

    Objectives: Changes in the way dietary fat is metabolized can be considered causative in obesity. The role of sedentary behavior in this defect has not been determined. We hypothesized that physical inactivity partitions dietary fats toward storage and that a resistance exercise training program mitigates storage. Design: We used bed rest, with randomization to resistance training, as a model of physical inactivity. Setting: The trial took place at the Space Clinic (Toulouse, France). Participants: A total of 18 healthy male volunteers, of mean age ± standard deviation 32.6 ± 4.0 y and body mass index 23.6 ± 0.7 kg/m2, were enrolled. Interventions: An initial 15 d of baseline data collection were followed by 3 mo of strict bed-rest alone (control group, n = 9) or with the addition of supine resistance exercise training every 3 d (exercise group, n = 9). Outcome measures: Oxidation of labeled [d31]palmitate (the main saturated fatty acid of human diet) and [1-13C]oleate (the main monounsaturated fatty acid), body composition, net substrate use, and plasma hormones and metabolites were measured. Results: Between-group comparisons showed that exercise training did not affect oxidation of both oleate (mean difference 5.6%; 95% confidence interval [95% CI], −3.3% to 14.5%; p = 0.20) and palmitate (mean difference −0.2%; 95% CI, −4.1% to 3.6%; p = 0.89). Within-group comparisons, however, showed that inactivity changed oxidation of palmitate in the control group by −11.0% (95% CI, −19.0% to −2.9%; p = 0.01) and in the exercise group by −11.3% (95% CI, −18.4% to −4.2%; p = 0.008). In contrast, bed rest did not significantly affect oleate oxidation within groups. In the control group, the mean difference in oleate oxidation was 3.2% (95% CI, −4.2% to 10.5%; p = 0.34) and 6.8% (95% CI, −1.2% to 14.7%; p = 0.08) in the exercise group. Conclusions: Independent of changes in energy balance (intake and/or output), physical inactivity decreased the

  9. Microplate-based active/inactive 1° screen for biomass degrading enzyme library purification and gene discovery.

    PubMed

    Wagschal, Kurt; Lee, Charles C

    2012-04-01

    We present here a whole-cell and permeabilized E. coli cell 1° active/inactive microplate screen for β-d-xylosidase, xylanase, endoglucanase, and ferulic acid esterase enzyme activities, which are critical for the enzymatic deconstruction of biomass for fuels and chemicals. Transformants from genomic or mutagenesis-derived libraries are screened using fluorophore-tagged substrate/enzyme activity pairs that are assayed directly in the protein expression host growth media using a minimum of specialized equipment and supplies. PMID:22285853

  10. Crystallographic studies of [NiFe]-hydrogenase mutants: towards consensus structures for the elusive unready oxidized states.

    PubMed

    Volbeda, Anne; Martin, Lydie; Barbier, Elodie; Gutiérrez-Sanz, Oscar; De Lacey, Antonio L; Liebgott, Pierre-Pol; Dementin, Sébastien; Rousset, Marc; Fontecilla-Camps, Juan C

    2015-01-01

    Catalytically inactive oxidized O2-sensitive [NiFe]-hydrogenases are characterized by a mixture of the paramagnetic Ni-A and Ni-B states. Upon O2 exposure, enzymes in a partially reduced state preferentially form the unready Ni-A state. Because partial O2 reduction should generate a peroxide intermediate, this species was previously assigned to the elongated Ni-Fe bridging electron density observed for preparations of [NiFe]-hydrogenases known to contain the Ni-A state. However, this proposition has been challenged based on the stability of this state to UV light exposure and the possibility of generating it anaerobically under either chemical or electrochemical oxidizing conditions. Consequently, we have considered alternative structures for the Ni-A species including oxidation of thiolate ligands to either sulfenate or sulfenic acid. Here, we report both new and revised [NiFe]-hydrogenases structures and conclude, taking into account corresponding characterizations by Fourier transform infrared spectroscopy (FTIR), that the Ni-A species contains oxidized cysteine and bridging hydroxide ligands instead of the peroxide ligand we proposed earlier. Our analysis was rendered difficult by the typical formation of mixtures of unready oxidized states that, furthermore, can be reduced by X-ray induced photoelectrons. The present study could be carried out thanks to the use of Desulfovibrio fructosovorans [NiFe]-hydrogenase mutants with special properties. In addition to the Ni-A state, crystallographic results are also reported for two diamagnetic unready states, allowing the proposal of a revised oxidized inactive Ni-SU model and a new structure characterized by a persulfide ion that is assigned to an Ni-'Sox' species. PMID:25315838

  11. Overcoming the risk of inaction from emissions uncertainty in smallholder agriculture

    NASA Astrophysics Data System (ADS)

    Berry, N. J.; Ryan, C. M.

    2013-03-01

    The potential for improving productivity and increasing the resilience of smallholder agriculture, while also contributing to climate change mitigation, has recently received considerable political attention (Beddington et al 2012). Financial support for improving smallholder agriculture could come from performance-based funding including sale of carbon credits or certified commodities, payments for ecosystem services, and nationally appropriate mitigation action (NAMA) budgets, as well as more traditional sources of development and environment finance. Monitoring the greenhouse gas fluxes associated with changes to agricultural practice is needed for performance-based mitigation funding, and efforts are underway to develop tools to quantify mitigation achieved and assess trade-offs and synergies between mitigation and other livelihood and environmental priorities (Olander 2012). High levels of small scale variability in carbon stocks and emissions in smallholder agricultural systems (Ziegler et al 2012) mean that data intensive approaches are needed for precise and unbiased mitigation monitoring. The cost of implementing such monitoring programmes is likely to be high, and this introduces the risk that projects will not be developed in areas where there is the greatest need for agricultural improvements, which are likely to correspond with areas where existing data or research infrastructure are lacking. When improvements to livelihoods and food security are expected as co-benefits of performance-based mitigation finance, the risk of inaction is borne by the rural poor as well as the global climate. In situ measurement of carbon accumulation in smallholders' soils are not usually feasible because of the costs associated with sampling in a heterogeneous landscape, although technological advances could improve the situation (Milori et al 2012). Alternatives to in situ measurement are to estimate greenhouse gas fluxes by extrapolating information from existing

  12. Methods of producing protoporphyrin IX and bacterial mutants therefor

    DOEpatents

    Zhou, Jizhong; Qiu, Dongru; He, Zhili; Xie, Ming

    2016-03-01

    The presently disclosed inventive concepts are directed in certain embodiments to a method of producing protoporphyrin IX by (1) cultivating a strain of Shewanella bacteria in a culture medium under conditions suitable for growth thereof, and (2) recovering the protoporphyrin IX from the culture medium. The strain of Shewanella bacteria comprises at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX. In certain embodiments of the method, the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or of shew_1140. In other embodiments, the presently disclosed inventive concepts are directed to mutant strains of Shewanella bacteria having at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX during cultivation of the bacteria. In certain embodiments the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or shew_1140.

  13. A computational study of λ-lac mutants

    NASA Astrophysics Data System (ADS)

    Werner, Maria; Aurell, Erik

    2009-12-01

    We present a comprehensive, computational study of the properties of bacteriophage λ mutants designed by Atsumi and Little (2006 Proc. Natl. Acad. Sci. 103 4558-63). These phages underwent a genetic reconstruction where Cro was replaced by a dimeric form of the Lac repressor. To clarify the theoretical characteristics of these mutants, we built a detailed thermodynamic model. The mutants all have a different genetic wiring than the wild-type λ. One group lacks regulation of PRM by the lytic protein. These mutants only exhibit the lysogenic equilibrium, with no transiently active PR. The other group lacks the negative feedback from CI. In this group, we identify a handful of bi-stable mutants, although the majority only exhibit the lysogenic equilibrium. The experimental identification of functional phages differs from our predictions. From a theoretical perspective, there is no reason why only 4 out of 900 mutants should be functional. The differences between theory and experiment can be explained in two ways. Either, the view of the λ phage as a bi-stable system needs to be revised, or the mutants have in fact not undergone a modular replacement, as intended by Atsumi and Little, but constitute instead a wider systemic change.

  14. Characterization of fig operon mutants of Francisella novicida U112

    PubMed Central

    Kiss, Katalin; Liu, Wei; Huntley, Jason F.; Norgard, Michael V.; Hansen, Eric J.

    2009-01-01

    Francisella species secrete a polycarboxylate siderophore that resembles rhizoferrin to acquire ferric iron. Several of the Francisella siderophore synthesis genes are contained in a Fur-regulated operon (designated fig or fsl) comprised of at least seven open reading frames (ORFs) including fur. Reverse transcriptase-PCR showed transcriptional linkage between figD and figE and between figE and figF. Mutations were constructed in four of these ORFs (figB, figC, figD, and figE) in F. novicida U112. All four of these new mutants and a F. novicida figA mutant grew at rates comparable to that of wild-type under iron-replete conditions but growth of all five mutants was stunted in iron-limiting media. When ferric rhizoferrin was added to the iron-limited media, growth of the figA, figB, figC, and figD mutants was restored to levels similar to those obtained in iron-replete media. However, this exogenously added siderophore could not rescue the figE mutant. When Chrome Azurol S assays were used to measure siderophore production, the figA, figB, and figC mutants were markedly deficient in their ability to synthesize siderophore whereas the figD and figE mutants produced siderophore at levels equivalent to the wild-type parent strain. PMID:18564336

  15. Subunit-specific phenotypes of Salmonella typhimurium HU mutants.

    PubMed Central

    Hillyard, D R; Edlund, M; Hughes, K T; Marsh, M; Higgins, N P

    1990-01-01

    Salmonella hupA and hupB mutants were studied to determine the reasons for the high degree of conservation in HU structure in bacteria. We found one HU-1-specific effect; the F'128 plasmid was 25-fold less stable in hupB compared with hupA or wild-type cells. F' plasmids were 120-fold more unstable in hupA hupB double mutants compared with wild-type cells, and the double mutant also had a significant alteration in plasmid DNA structure. pBR322 DNA isolated from hupA hupB strains was deficient in supercoiling by 10 to 15% compared with wild-type cells, and the topoisomer distribution was significantly more heterogeneous than in wild-type or single-mutant strains. Other systems altered by HU inactivation included flagellar phase variation and phage Mu transposition. However, Mu transposition rates were only about fourfold lower in Salmonella HU double mutants. One reason that Salmonella HU double mutants may be less defective for Mu transposition than E. coli is the synthesis in double mutants of a new, small, basic heat-stable protein, which might partially compensate for the loss of HU. The results indicate that although either HU-1 or HU-2 subunit alone may accommodate the cellular need for general chromosomal organization, the selective pressure to conserve HU-1 and HU-2 structure during evolution could involve specialized roles of the individual subunits. Images PMID:2168381

  16. New Salmonella typhimurium mutants with altered outer membrane permeability.

    PubMed Central

    Sukupolvi, S; Vaara, M; Helander, I M; Viljanen, P; Mäkelä, P H

    1984-01-01

    We describe three new classes of Salmonella typhimurium mutants with increased sensitivity to hydrophobic agents. In contrast to many previously described mutants, the phage sensitivity pattern of these mutants did not give any indication of defective lipopolysaccharide. Furthermore, they had no detectable changes in their phospholipid or outer membrane protein composition, and their growth rate and cell morphology were normal. Class B mutants were nearly as sensitive to novobiocin, fusidic acid, erythromycin, rifampin, and clindamycin as are deep rough (heptoseless) mutants; in addition they were sensitive to methicillin, penicillin (to which heptoseless mutants are resistant), gentian violet, and anionic and cationic detergents. Class A and C mutants had less sensitive, but characteristic phenotypes. None of the three classes were sensitive to serum bactericidal action. The class B mutation mapped between map positions 7 and 11 on the S. typhimurium chromosome, and the class C mutation mapped between positions 5 and 7. The map position for the class A mutation remained undefined, but it was separate from the class B and C mutations and, like those, did not correspond to any gene loci known to participate in the synthesis of major outer membrane constituents. Images PMID:6378889

  17. Mapping Pathological Phenotypes in Reelin Mutant Mice

    PubMed Central

    Michetti, Caterina; Romano, Emilia; Altabella, Luisa; Caruso, Angela; Castelluccio, Paolo; Bedse, Gaurav; Gaetani, Silvana; Canese, Rossella; Laviola, Giovanni; Scattoni, Maria Luisa

    2014-01-01

    Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male–female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype. PMID

  18. Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity.

    PubMed

    Sun, Xin; Marque, Leonard O; Cordner, Zachary; Pruitt, Jennifer L; Bhat, Manik; Li, Pan P; Kannan, Geetha; Ladenheim, Ellen E; Moran, Timothy H; Margolis, Russell L; Rudnicki, Dobrila D

    2014-12-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT. Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein. Antisense oligonucleotides (ASOs) targeted to the CAG repeat region of HTT transcripts have been of particular interest due to their potential capacity to discriminate between normal and mutant HTT transcripts. Here, we focus on phosphorodiamidate morpholino oligomers (PMOs), ASOs that are especially stable, highly soluble and non-toxic. We designed three PMOs to selectively target expanded CAG repeat tracts (CTG22, CTG25 and CTG28), and two PMOs to selectively target sequences flanking the HTT CAG repeat (HTTex1a and HTTex1b). In HD patient-derived fibroblasts with expanded alleles containing 44, 77 or 109 CAG repeats, HTTex1a and HTTex1b were effective in suppressing the expression of mutant and non-mutant transcripts. CTGn PMOs also suppressed HTT expression, with the extent of suppression and the specificity for mutant transcripts dependent on the length of the targeted CAG repeat and on the CTG repeat length and concentration of the PMO. PMO CTG25 reduced HTT-induced cytotoxicity in vitro and suppressed mutant HTT expression in vivo in the N171-82Q transgenic mouse model. Finally, CTG28 reduced mutant HTT expression and improved the phenotype of Hdh(Q7/Q150) knock-in HD mice. These data demonstrate the potential of PMOs as an approach to suppressing the expression of mutant HTT. PMID:25035419

  19. Angelman syndrome-associated ubiquitin ligase UBE3A/E6AP mutants interfere with the proteolytic activity of the proteasome

    PubMed Central

    Tomaić, V; Banks, L

    2015-01-01

    Angelman syndrome, a severe neurodevelopmental disease, occurs primarily due to genetic defects, which cause lack of expression or mutations in the wild-type E6AP/UBE3A protein. A proportion of the Angelman syndrome patients bear UBE3A point mutations, which do not interfere with the expression of the full-length protein, however, these individuals still develop physiological conditions of the disease. Interestingly, most of these mutations are catalytically defective, thereby indicating the importance of UBE3A enzymatic activity role in the Angelman syndrome pathology. In this study, we show that Angelman syndrome-associated mutants interact strongly with the proteasome via the S5a proteasomal subunit, resulting in an overall inhibitory effect on the proteolytic activity of the proteasome. Our results suggest that mutated catalytically inactive forms of UBE3A may cause defects in overall proteasome function, which could have an important role in the Angelman syndrome pathology. PMID:25633294

  20. Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells

    SciTech Connect

    Harnicarova, Andrea; Kozubek, Stanislav . E-mail: kozubek@ibp.cz; Pachernik, Jiri; Krejci, Jana; Bartova, Eva

    2006-12-10

    Using sequential RNA-DNA fluorescence in situ hybridization, the nuclear arrangement of both the active and inactive c-myc gene as well as its transcription was investigated in colon cancer HT-29 cells induced to differentiate into enterocytes. Cytogenetic studies revealed the presence of two chromosomes 8 in HT-29 cells, of which the one containing c-myc gene amplicons was substantially larger and easily distinguished from the normal chromosome. This observation enabled detection of both activity and nuclear localization of c-myc genes in single cells and in individual chromosome territories. Similar transcriptional activity of the c-myc gene was observed in both the normal and derivative chromosome 8 territories showing no influence of the amplification on the c-myc gene expression. Our experiments demonstrate strikingly specific nuclear and territorial arrangements of active genes as compared with inactive ones: on the periphery of their territories facing to the very central region of the cell nucleus. Nuclear arrangement of c-myc genes and transcripts was conserved during cell differentiation and, therefore, independent of the level of differentiation-specific c-myc gene expression. However, after the induction of differentiation, a more internal territorial location was found for the single copy c-myc gene of normal chromosome 8, while amplicons conserved their territorial topography.