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1

TCA cycle activity in Saccharomyces cerevisiae is a function of the environmentally determined specific growth and glucose uptake rates.  

PubMed

Metabolic responses of Saccharomyces cerevisiae to different physical and chemical environmental conditions were investigated in glucose batch culture by GC-MS-detected mass isotopomer distributions in proteinogenic amino acids from (13)C-labelling experiments. For this purpose, GC-MS-based metabolic flux ratio analysis was extended from bacteria to the compartmentalized metabolism of S. cerevisiae. Generally, S. cerevisiae was shown to have low catabolic fluxes through the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. Notably, respiratory TCA cycle fluxes exhibited a strong correlation with the maximum specific growth rate that was attained under different environmental conditions, including a wide range of pH, osmolarity, decoupler and salt concentrations, but not temperature. At pH values of 4.0 to 6.0 with near-maximum growth rates, the TCA cycle operated as a bifurcated pathway to fulfil exclusively biosynthetic functions. Increasing or decreasing the pH beyond this physiologically optimal range, however, reduced growth and glucose uptake rates but increased the 'cyclic' respiratory mode of TCA cycle operation for catabolism. Thus, the results indicate that glucose repression of the TCA cycle is regulated by the rates of growth or glucose uptake, or signals derived from these. While sensing of extracellular glucose concentrations has a general influence on the in vivo TCA cycle activity, the growth-rate-dependent increase in respiratory TCA cycle activity was independent of glucose sensing. PMID:15073318

Blank, Lars M; Sauer, Uwe

2004-04-01

2

Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.  

ERIC Educational Resources Information Center

Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

Bodner, George M.

1986-01-01

3

ABNORMALITIES IN THE TRICARBOXYLIC ACID (TCA) CYCLE IN BRAIN OF SCHIZOPHRENIA PATIENTS  

PubMed Central

Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, p<0.05), KGDHC (26%) and STH (28.2%, p<0.05), enzymes in the first half of the TCA cycle, were lower, but SDH (18.3%, p<0.05) and MDH (34%, p<0.005), enzymes in the second half, were higher than controls. PDHC, CS, ICDH and fumarase activities were unchanged. There were no significant correlations between enzymes of TCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r=0.55, p=003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia.

Bubber, P; Hartounian, V; Gibson, GE; Blass, JP

2010-01-01

4

Citrate as a Flying Bird: Useful Mnemonics in Teaching the TCA Cycle  

NASA Astrophysics Data System (ADS)

A novel tip is recommended: to use the similarity of the citrate molecule to the schematic of a bird. The proposed mnemonics also enable students to draw the chemical structures of two more key TCA cycle intermediates, succinate and malate.

Kozliak, Evguenii I.

1999-12-01

5

Prebiotic Metabolisms: Photo catalysis of the rTCA cycle by sphalerite colloids  

Microsoft Academic Search

Explorations of mineral catalyzed reverse tricarboxylic acid (rTCA) cycle reactions provide a window into possible mechanisms for prebiotic metabolisms and the origins of life. The excitation of nano-scale semiconducting sphalerite minerals by ultra-violate light results in reducing electrons capable of catalyzing the reduction reactions present in the rTCA cycle. Current literature has utilized ion chromatography methods to characterize catalysis of

D. M. Mangiante; B. Bowen; T. Northen; J. F. Banfield

2010-01-01

6

Cofactor Balance by Nicotinamide Nucleotide Transhydrogenase (NNT) Coordinates Reductive Carboxylation and Glucose Catabolism in the Tricarboxylic Acid (TCA) Cycle*?  

PubMed Central

Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of ?-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)+ cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)+ ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle.

Gameiro, Paulo A.; Laviolette, Laura A.; Kelleher, Joanne K.; Iliopoulos, Othon; Stephanopoulos, Gregory

2013-01-01

7

Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle.  

PubMed

Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of ?-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)(+) cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)(+) ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle. PMID:23504317

Gameiro, Paulo A; Laviolette, Laura A; Kelleher, Joanne K; Iliopoulos, Othon; Stephanopoulos, Gregory

2013-05-01

8

Cataplerotic TCA cycle flux determined as glutamate-sustained oxygen consumption in primary cultures of astrocytes  

Microsoft Academic Search

Utilization of glucose by adult brain as its metabolic substrate does not mean that glutamate cannot be synthesized from glucose and subsequently oxidatively degraded. Between 10 and 20% of total pyruvate metabolism in brain occurs as formation of oxaloacetate (OAA), a tricarboxylic acid (TCA) cycle intermediate, from pyruvate plus CO2. This anaplerotic (‘pool-filling’) process occurs in astrocytes, which in contrast

Leif Hertz; Elna Hertz

2003-01-01

9

A mitochondrial GABA permease connects the GABA shunt and the TCA cycle, and is essential for normal carbon metabolism.  

PubMed

In plants, ?-aminobutyric acid (GABA) accumulates in the cytosol in response to a variety of stresses. GABA is transported into mitochondria, where it is catabolized into TCA cycle or other intermediates. Although there is circumstantial evidence for mitochondrial GABA transporters in eukaryotes, none have yet been identified. Described here is an Arabidopsis protein similar in sequence and topology to unicellular GABA transporters. The expression of this protein complements a GABA-transport-deficient yeast mutant. Thus the protein was termed AtGABP to indicate GABA-permease activity. In vivo localization of GABP fused to GFP and immunobloting of subcellular fractions demonstrate its mitochondrial localization. Direct [(3) H]GABA uptake measurements into isolated mitochondria revealed impaired uptake into mitochondria of a gabp mutant compared with wild-type (WT) mitochondria, implicating AtGABP as a major mitochondrial GABA carrier. Measurements of CO(2) release, derived from radiolabeled substrates in whole seedlings and in isolated mitochondria, demonstrate impaired GABA-derived input into the TCA cycle, and a compensatory increase in TCA cycle activity in gabp mutants. Finally, growth abnormalities of gabp mutants under limited carbon availability on artificial media, and in soil under low light intensity, combined with their metabolite profiles, suggest an important role for AtGABP in primary carbon metabolism and plant growth. Thus, AtGABP-mediated transport of GABA from the cytosol into mitochondria is important to ensure proper GABA-mediated respiration and carbon metabolism. This function is particularly essential for plant growth under conditions of limited carbon. PMID:21501262

Michaeli, Simon; Fait, Aaron; Lagor, Kelly; Nunes-Nesi, Adriano; Grillich, Nicole; Yellin, Ayelet; Bar, Dana; Khan, Munziba; Fernie, Alisdair R; Turano, Frank J; Fromm, Hillel

2011-08-01

10

Cataplerotic TCA cycle flux determined as glutamate-sustained oxygen consumption in primary cultures of astrocytes.  

PubMed

Utilization of glucose by adult brain as its metabolic substrate does not mean that glutamate cannot be synthesized from glucose and subsequently oxidatively degraded. Between 10 and 20% of total pyruvate metabolism in brain occurs as formation of oxaloacetate (OAA), a tricarboxylic acid (TCA) cycle intermediate, from pyruvate plus CO(2). This anaplerotic ('pool-filling') process occurs in astrocytes, which in contrast to neurons express pyruvate carboxylase (PC) activity. Equivalent amounts of pyruvate are converted to acetylcoenzyme A and condensed with oxaloacetate to form citrate (Cit), which is metabolized to alpha-ketoglutarate (generating oxidatively-derived energy), glutamate and glutamine and transferred to neurons in the glutamate-glutamine cycle and used as precursor for transmitter glutamate. Since the blood-brain barrier is poorly permeable to glutamate and its metabolites, net synthesis of glutamate must be followed by degradation of equivalent amounts of glutamate, a cataplerotic ('pool-emptying') process, in which glutamate is converted in the TCA cycle to malate or oxaloacetate (generating additional energy), which exit the cycle to form one molecule pyruvate. To obtain an estimate of the rate of astrocytic oxidation of glutamate the rate of oxygen consumption was measured in primary cultures of mouse astrocytes metabolizing glutamate in the absence of other metabolic substrates. The observed rate is compatible with complete oxidative degradation of glutamate. PMID:12742079

Hertz, Leif; Hertz, Elna

2003-01-01

11

Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells  

PubMed Central

Summary The TCA cycle is the central hub of oxidative metabolism, running in the classic forward direction to provide carbon for biosynthesis and reducing agents for generation of ATP. Our metabolic tracer studies in melanoma cells showed that in hypoxic conditions the TCA cycle is largely disconnected from glycolysis. By studying the TCA branch point metabolites, acetyl CoA and citrate, as well as the metabolic endpoints glutamine and fatty acids, we developed a comprehensive picture of the rewiring of the TCA cycle that occurs in hypoxia. Hypoxic tumor cells maintain proliferation by running the TCA cycle in reverse. The source of carbon for acetyl CoA, citrate, and fatty acids switches from glucose in normoxia to glutamine in hypoxia. This hypoxic flux from glutamine into fatty acids is mediated by reductive carboxylation. This reductive carboxylation is catalyzed by two isocitrate dehydrogenases, IDH1 and IDH2. Their combined action is necessary and sufficient to effect the reverse TCA flux and maintain cellular viability.

Filipp, Fabian V.; Scott, David A.; Ronai, Ze'ev A.; Osterman, Andrei L.; Smith, Jeffrey W.

2012-01-01

12

Improving the description of metabolic networks: the TCA cycle as example.  

PubMed

To collect the ever-increasing yet scattered knowledge on metabolism, multiple pathway databases like the Kyoto Encyclopedia of Genes and Genomes have been created. A complete and accurate description of the metabolic network for human and other organisms is essential to foster new biological discoveries. Previous research has shown, however, that the level of agreement among pathway databases is surprisingly low. We investigated whether the lack of consensus among databases can be explained by an inaccurate representation of the knowledge described in scientific literature. As an example, we focus on the well-known tricarboxylic acid (TCA) cycle and evaluated the description of this pathway as found in a comprehensive selection of 10 human metabolic pathway databases. Remarkably, none of the descriptions given by these databases is entirely correct. Moreover, consensus exists on only 3 reactions. Mistakes in pathway databases might lead to the propagation of incorrect knowledge, misinterpretation of high-throughput molecular data, and poorly designed follow-up experiments. We provide an improved description of the TCA cycle via the community-curated database WikiPathways. We review various initiatives that aim to improve the description of the human metabolic network and discuss the importance of the active involvement of biological experts in these. PMID:22661004

Stobbe, Miranda D; Houten, Sander M; van Kampen, Antoine H C; Wanders, Ronald J A; Moerland, Perry D

2012-09-01

13

Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells  

PubMed Central

Summary Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using Stable Isotope Resolved Metabolomics. Using [U-13C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-13C,15N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, and glutamine contributed significantly to citrate carbons. Under glucose deprivation, glutamine-derived fumarate, malate, and citrate were significantly increased. Their 13C labeling patterns demonstrate an alternative energy-generating glutaminolysis pathway involving a glucose-independent TCA cycle. The essential role of glutamine metabolism in cell survival and proliferation under hypoxia and glucose deficiency, makes them susceptible to the glutaminase inhibitor BPTES, and hence could be targeted for cancer therapy.

Le, Anne; Lane, Andrew N.; Hamaker, Max; Bose, Sminu; Gouw, Arvin; Barbi, Joseph; Tsukamoto, Takashi; Rojas, Camilio J.; Slusher, Barbara S.; Zhang, Haixia; Zimmerman, Lisa J.; Liebler, Daniel C.; Slebos, Robbert J.C.; Lorkiewicz, Pawel K.; Higashi, Richard M.; Fan, Teresa W. M.; Dang, Chi V.

2012-01-01

14

TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells  

PubMed Central

Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts of nitric oxide (NO•) and an inducible nitric oxide synthase as compared to those cells exposed to wild-type bacteria. Despite the decrease in NO• synthesis, the expression of antigen-presentation and costimulatory molecules was similar in cells cultured with wild-type and those cultured with aconitase mutant bacteria. The data suggest that staphylococci can evade innate immune responses and potentially enhance their ability to survive in infected hosts by altering their metabolism. This may also explain the occurrence of TCA cycle mutants in clinical S. aureus isolates.

Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Gardner, Donald J.; Musser, James M.; Steffen, David; Somerville, Greg A.

2013-01-01

15

Excessive Hepatic Mitochondrial TCA Cycle and Gluconeogenesis in Humans with Nonalcoholic Fatty Liver Disease  

PubMed Central

Summary Approximately one-third of the U.S. population has nonalcoholic fatty liver disease (NAFLD), a condition closely associated with insulin resistance and increased risk of liver injury. Dysregulated mitochondrial metabolism is central in these disorders, but the manner and degree of dysregulation are disputed. This study tested whether humans with NAFLD have abnormal in vivo hepatic mitochondrial metabolism. Subjects with low (3.0%) and high (17%) intrahepatic triglyceride (IHTG) were studied using 2H and 13C tracers to evaluate systemic lipolysis, hepatic glucose production, and mitochondrial pathways (TCA cycle, anaplerosis, and ketogenesis). Individuals with NAFLD had 50% higher rates of lipolysis and 30% higher rates of gluconeogenesis. There was a positive correlation between IHTG content and both mitochondrial oxidative and anaplerotic fluxes. These data indicate that mitochondrial oxidative metabolism is ?2-fold greater in those with NAFLD, providing a potential link between IHTG content, oxidative stress, and liver damage.

Sunny, Nishanth E.; Parks, Elizabeth J.; Browning, Jeffrey D.; Burgess, Shawn C.

2013-01-01

16

Anaerobic Respiration Using a Complete Oxidative TCA Cycle Drives Multicellular Swarming in Proteus mirabilis  

PubMed Central

ABSTRACT Proteus mirabilis rapidly migrates across surfaces using a periodic developmental process of differentiation alternating between short swimmer cells and elongated hyperflagellated swarmer cells. To undergo this vigorous flagellum-mediated motility, bacteria must generate a substantial proton gradient across their cytoplasmic membranes by using available energy pathways. We sought to identify the link between energy pathways and swarming differentiation by examining the behavior of defined central metabolism mutants. Mutations in the tricarboxylic acid (TCA) cycle (fumC and sdhB mutants) caused altered patterns of swarming periodicity, suggesting an aerobic pathway. Surprisingly, the wild-type strain swarmed on agar containing sodium azide, which poisons aerobic respiration; the fumC TCA cycle mutant, however, was unable to swarm on azide. To identify other contributing energy pathways, we screened transposon mutants for loss of swarming on sodium azide and found insertions in the following genes that involved fumarate metabolism or respiration: hybB, encoding hydrogenase; fumC, encoding fumarase; argH, encoding argininosuccinate lyase (generates fumarate); and a quinone hydroxylase gene. These findings validated the screen and suggested involvement of anaerobic electron transport chain components. Abnormal swarming periodicity of fumC and sdhB mutants was associated with the excretion of reduced acidic fermentation end products. Bacteria lacking SdhB were rescued to wild-type pH and periodicity by providing fumarate, independent of carbon source but dependent on oxygen, while fumC mutants were rescued by glycerol, independent of fumarate only under anaerobic conditions. These findings link multicellular swarming patterns with fumarate metabolism and membrane electron transport using a previously unappreciated configuration of both aerobic and anaerobic respiratory chain components.

Alteri, Christopher J.; Himpsl, Stephanie D.; Engstrom, Michael D.; Mobley, Harry L. T.

2012-01-01

17

Real Time Molecular Imaging of TCA Cycle Metabolism in vivo By Hyperpolarized 1-13C Diethyl Succinate  

PubMed Central

The Krebs tricarboxylic acid cycle (TCA) is central to metabolic energy production and is known to be altered in many disease states. Real time molecular imaging of TCA cycle in vivo will be important in understanding the metabolic basis of several diseases. Positron emission tomography (PET) using FDG-glucose (2-[18F]fluoro-2-deoxy-D-glucose) is already being used as a metabolic imaging agent in clinics. However, FDG-glucose does not reveal anything past glucose uptake and phosphorylation. We have developed a new metabolic imaging agent, hyperpolarized diethyl 1-13C 2,3-d2 succinate, that allows for real time in vivo imaging and spectroscopy of the TCA cycle. Diethyl succinate can be hyperpolarized using parahydrogen induced polarization (PHIP) in an aqueous solution with signal enhancement of 5000 compared to Boltzmann polarization. 13C magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) were achieved in vivo seconds after injection of 10 to 20 ?mol of hyperpolarized diethyl succinate into normal mice. The downstream metabolites of hyperpolarized diethyl succinate were identified in vivo as malate, succinate, fumarate and aspartate. The metabolism of diethyl succinate was altered after exposing the animal to 3-nitropropionate, a known irreversible inhibitor of succinate dehydrogenase. Based on our results, hyperpolarized diethyl succinate allows for in real time in vivo MRI and MRS with a high signal to noise ratio and with visualization of multiple steps of the TCA cycle. Hyperpolarization of diethyl succinate and its in vivo applications may reveal an entirely new regime wherein the local status of TCA cycle metabolism is interrogated on the time scale of seconds to minutes with unprecedented chemical specificity and MR sensitivity.

Zacharias, Niki M.; Chan, Henry R.; Sailasuta, Napapon; Ross, Brian D.

2011-01-01

18

Isotopomer Profiling of Leishmania mexicana Promastigotes Reveals Important Roles for Succinate Fermentation and Aspartate Uptake in Tricarboxylic Acid Cycle (TCA) Anaplerosis, Glutamate Synthesis, and Growth*  

PubMed Central

Leishmania parasites proliferate within nutritionally complex niches in their sandfly vector and mammalian hosts. However, the extent to which these parasites utilize different carbon sources remains poorly defined. In this study, we have followed the incorporation of various 13C-labeled carbon sources into the intracellular and secreted metabolites of Leishmania mexicana promastigotes using gas chromatography-mass spectrometry and 13C NMR. [U-13C]Glucose was rapidly incorporated into intermediates in glycolysis, the pentose phosphate pathway, and the cytoplasmic carbohydrate reserve material, mannogen. Enzymes involved in the upper glycolytic pathway are sequestered within glycosomes, and the ATP and NAD+ consumed by these reactions were primarily regenerated by the fermentation of phosphoenolpyruvate to succinate (glycosomal succinate fermentation). The initiating enzyme in this pathway, phosphoenolpyruvate carboxykinase, was exclusively localized to the glycosome. Although some of the glycosomal succinate was secreted, most of the C4 dicarboxylic acids generated during succinate fermentation were further catabolized in the TCA cycle. A high rate of TCA cycle anaplerosis was further suggested by measurement of [U-13C]aspartate and [U-13C]alanine uptake and catabolism. TCA cycle anaplerosis is apparently needed to sustain glutamate production under standard culture conditions. Specifically, inhibition of mitochondrial aconitase with sodium fluoroacetate resulted in the rapid depletion of intracellular glutamate pools and growth arrest. Addition of high concentrations of exogenous glutamate alleviated this growth arrest. These findings suggest that glycosomal and mitochondrial metabolism in Leishmania promastigotes is tightly coupled and that, in contrast to the situation in some other trypanosomatid parasites, the TCA cycle has crucial anabolic functions.

Saunders, Eleanor C.; Ng, William W.; Chambers, Jennifer M.; Ng, Milica; Naderer, Thomas; Kromer, Jens O.; Likic, Vladimir A.; McConville, Malcolm J.

2011-01-01

19

An Incomplete TCA Cycle Increases Survival of Salmonella Typhimurium during Infection of Resting and Activated Murine Macrophages  

Microsoft Academic Search

BackgroundIn comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice.Methodology\\/Principal FindingsWe constructed deletion mutations of

Steven D. Bowden; Vinoy K. Ramachandran; Gitte M. Knudsen; Jay C. D. Hinton; Arthur Thompson; Robin Charles May

2010-01-01

20

Coordinated activation of PTA-ACS and TCA cycles strongly reduces overflow metabolism of acetate in Escherichia coli.  

PubMed

Elimination of acetate overflow in aerobic cultivation of Escherichia coli would improve many bioprocesses as acetate accumulation in the growth environment leads to numerous negative effects, e.g. loss of carbon, inhibition of growth, target product synthesis, etc. Despite many years of studies, the mechanism and regulation of acetate overflow are still not completely understood. Therefore, we studied the growth of E. coli K-12 BW25113 and several of its mutant strains affecting acetate-related pathways using the continuous culture method accelerostat (A-stat) at various specific glucose consumption rates with the aim of diminishing acetate overflow. Absolute quantitative exo-metabolome and proteome analyses coupled to metabolic flux analysis enabled us to demonstrate that onset of acetate overflow can be postponed and acetate excretion strongly reduced in E. coli by coordinated activation of phosphotransacetylase-acetyl-CoA synthetase (PTA-ACS) and tricarboxylic acid (TCA) cycles. Fourfold reduction of acetate excretion (2 vs. 8 % from total carbon) at fastest growth compared to wild type was achieved by deleting the genes responsible for inactivation of acetyl-CoA synthetase protein (pka) and TCA cycle regulator arcA. The ?pka ?arcA strain did not accumulate any other detrimental by-product besides acetate and showed identical ? max and only ~5 % lower biomass yield compared to wild type. We conclude that a fine-tuned coordination between increasing the recycling capabilities of acetate in the PTA-ACS node through a higher concentration of active acetate scavenging Acs protein and downstream metabolism throughput in the TCA cycle is necessary for diminishing overflow metabolism of acetate in E. coli and achieving higher target product production in bioprocesses. PMID:24633370

Peebo, Karl; Valgepea, Kaspar; Nahku, Ranno; Riis, Gethe; Oun, Mikk; Adamberg, Kaarel; Vilu, Raivo

2014-06-01

21

Exposure of clinical MRSA heterogeneous strains to ?-lactams redirects metabolism to optimize energy production through the TCA cycle.  

PubMed

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important pathogens both in health care and community-onset infections. The prerequisite for methicillin resistance is mecA, which encodes a ?-lactam-insensitive penicillin binding protein PBP2a. A characteristic of MRSA strains from hospital and community associated infections is their heterogeneous expression of resistance to ?-lactam (HeR) in which only a small portion (? 0.1%) of the population expresses resistance to oxacillin (OXA) ? 10 µg/ml, while in other isolates, most of the population expresses resistance to a high level (homotypic resistance, HoR). The mechanism associated with heterogeneous expression requires both increase expression of mecA and a mutational event that involved the triggering of a ?-lactam-mediated SOS response and related lexA and recA genes. In the present study we investigated the cellular physiology of HeR-MRSA strains during the process of ?-lactam-mediated HeR/HoR selection at sub-inhibitory concentrations by using a combinatorial approach of microarray analyses and global biochemical profiling employing gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) to investigate changes in metabolic pathways and the metabolome associated with ?-lactam-mediated HeR/HoR selection in clinically relevant heterogeneous MRSA. We found unique features present in the oxacillin-selected SA13011-HoR derivative when compared to the corresponding SA13011-HeR parental strain that included significant increases in tricarboxyl citric acid (TCA) cycle intermediates and a concomitant decrease in fermentative pathways. Inactivation of the TCA cycle enzyme cis-aconitase gene in the SA13011-HeR strain abolished ?-lactam-mediated HeR/HoR selection demonstrating the significance of altered TCA cycle activity during the HeR/HoR selection. These results provide evidence of both the metabolic cost and the adaptation that HeR-MRSA clinical strains undergo when exposed to ?-lactam pressure, indicating that the energy production is redirected to supply the cell wall synthesis/metabolism, which in turn contributes to the survival response in the presence of ?-lactam antibiotics. PMID:23940684

Keaton, Mignon A; Rosato, Roberto R; Plata, Konrad B; Singh, Christopher R; Rosato, Adriana E

2013-01-01

22

Fitness of Escherichia coli during Urinary Tract Infection Requires Gluconeogenesis and the TCA Cycle  

Microsoft Academic Search

Microbial pathogenesis studies traditionally encompass dissection of virulence properties such as the bacterium's ability to elaborate toxins, adhere to and invade host cells, cause tissue damage, or otherwise disrupt normal host immune and cellular functions. In contrast, bacterial metabolism during infection has only been recently appreciated to contribute to persistence as much as their virulence properties. In this study, we

Christopher J. Alteri; Sara N. Smith; Harry L. T. Mobley

2009-01-01

23

Possible links between stress defense and the tricarboxylic acid (TCA) cycle in Francisella pathogenesis.  

PubMed

Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. In vivo, this facultative intracellular bacterium survives and replicates mainly in the cytoplasm of infected cells. We have recently identified a genetic locus, designated moxR that is important for stress resistance and intramacrophage survival of F. tularensis. In the present work, we used tandem affinity purification coupled to mass spectrometry to identify in vivo interacting partners of three proteins encoded by this locus: the MoxR-like ATPase (FTL_0200), and two proteins containing motifs predicted to be involved in protein-protein interactions, bearing von Willebrand A (FTL_0201) and tetratricopeptide (FTL_0205) motifs. The three proteins were designated here for simplification, MoxR, VWA1, and TPR1, respectively. MoxR interacted with 31 proteins, including various enzymes. VWA1 interacted with fewer proteins, but these included the E2 component of 2-oxoglutarate dehydrogenase and TPR1. The protein TPR1 interacted with one hundred proteins, including the E1 and E2 subunits of both oxoglutarate and pyruvate dehydrogenase enzyme complexes, and their common E3 subunit. Remarkably, chromosomal deletion of either moxR or tpr1 impaired pyruvate dehydrogenase and oxoglutarate dehydrogenase activities, supporting the hypothesis of a functional role for the interaction of MoxR and TPR1 with these complexes. Altogether, this work highlights possible links between stress resistance and metabolism in F. tularensis virulence. PMID:23669032

Dieppedale, Jennifer; Gesbert, Gael; Ramond, Elodie; Chhuon, Cerina; Dubail, Iharilalao; Dupuis, Marion; Guerrera, Ida Chiara; Charbit, Alain

2013-08-01

24

Modulation of key enzymes of glycolysis, gluconeogenesis, amino acid catabolism, and TCA cycle of the tropical freshwater fish Labeo rohita fed gelatinized and non-gelatinized starch diet  

Microsoft Academic Search

A 60-day experiment was conducted to study the effect of dietary gelatinized (G) and non-gelatinized (NG) starch on the key\\u000a metabolic enzymes of glycolysis (hexokinase, glucokinase, pyruvate kinase, and lactate dehydrogenase), gluconeogenesis (glucose-6\\u000a phosphatase and fructose-1,6 bisphosphatase), protein metabolism (aspartate amino transferase and alanine amino transferase),\\u000a and TCA cycle (malate dehydrogenase) in Labeo rohita juveniles. In the analysis, 234 juveniles

Vikas Kumar; N. P. Sahu; A. K. Pal; Shivendra Kumar; Amit Kumar Sinha; Jayant Ranjan; Kartik Baruah

2010-01-01

25

The Majority of Free-Living Autotrophic Bacteria use the Reductive TCA Cycle for Carbon Fixation at Deep-Sea Hydrothermal Vents  

NASA Astrophysics Data System (ADS)

Deep-sea hydrothermal vents support large micro and macroscopic communities, without the input of photosynthesis. Autotrophic production at these vents is based on hydrothermal vent fluid chemistry. Primary production has been thought to occur mainly via hydrogen sulfide oxidation through the Calvin-Benson pathway, as measured by the presence of Rubisco in endosymbionts of several invertebrate hosts. Recently, we characterized two fosmids from a large insert library of the epsilon Proteobacterial episymbionts of Alvinella pompejana. Both contained sequences encoding ATP citrate lyase, a key enzyme in the reverse TCA cycle, an alternate carbon dioxide fixation pathway. Previous investigators have demonstrated the dominance of the epsilon subdivision in the free-living bacterial communities at hydrothermal vents. Based on these results, our working hypothesis is: The rTCA cycle is the dominant pathway for carbon fixation in the free-living bacterial communities at hydrothermal vents. A selection of free-living bacterial communities from various geographic locations (9N, East Pacific Rise and Guaymas Basin) were screened for the presence, diversity and expression (via RT-PCR) of Rubisco (forms I and II) and ATP citrate lyase. Our results indicate that the ATP citrate lyase gene is diverse and is consistently expressed in several types of vent communities. The two forms of Rubisco are not consistently present or expressed in the same environments. These results indicate that chemoautotrophic production in the free-living bacterial communities at deep-sea hydrothermal vents is dominated by bacteria that utilize the rTCA cycle, and parallels the phylogenetic dominance of members of the epsilon subdivision of Proteobacteria.

Campbell, B. J.; Cary, C.

2003-12-01

26

TCA Cycle-Mediated Generation of ROS Is a Key Mediator for HeR-MRSA Survival under ?-Lactam Antibiotic Exposure  

PubMed Central

Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of ?-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to ?-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to ?-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism.

Rosato, Roberto R.; Fernandez, Regina; Paz, Liliana I.; Singh, Christopher R.; Rosato, Adriana E.

2014-01-01

27

TCA Cycle-Mediated Generation of ROS Is a Key Mediator for HeR-MRSA Survival under ?-Lactam Antibiotic Exposure.  

PubMed

Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of ?-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to ?-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to ?-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism. PMID:24932751

Rosato, Roberto R; Fernandez, Regina; Paz, Liliana I; Singh, Christopher R; Rosato, Adriana E

2014-01-01

28

Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis  

PubMed Central

The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG). Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci.

Chang, Yu-Ming; Chen, Cammy K. -M.; Chang, Yuan-Chih; Jeng, Wen-Yih; Hou, Ming-Hon; Wang, Andrew H. -J.

2012-01-01

29

The Aspergillus nidulans acuL gene encodes a mitochondrial carrier required for the utilization of carbon sources that are metabolized via the TCA cycle.  

PubMed

In Aspergillus nidulans, the utilization of acetate as sole carbon source requires several genes (acu). Most of them are also required for the utilization of fatty acids. This is the case for acuD and acuE, which encode the two glyoxylate cycle-specific enzymes, isocitrate lyase and malate synthase, respectively, but also for acuL that we have identified as AN7287, and characterized in this study. Deletion of acuL resulted in the same phenotype as the original acuL217 mutant. acuL encodes a 322-amino acid protein which displays all the structural features of a mitochondrial membrane carrier, and shares 60% identity with the Saccharomyces cerevisiae succinate/fumarate mitochondrial antiporter Sfc1p (also named Acr1p). Consistently, the AcuL protein was shown to localize in mitochondria, and partial cross-complementation was observed between the S. cerevisiae and A. nidulans homologues. Extensive phenotypic characterization suggested that the acuL gene is involved in the utilization of carbon sources that are catabolized via the TCA cycle, and therefore require gluconeogenesis. In addition, acuL proves to be co-regulated with acuD and acuE. Overall, our data suggest that AcuL could link the glyoxylate cycle to gluconeogenesis by exchanging cytoplasmic succinate for mitochondrial fumarate. PMID:24835019

Flipphi, Michel; Oestreicher, Nathalie; Nicolas, Valérie; Guitton, Audrey; Vélot, Christian

2014-07-01

30

Increased anaplerosis, TCA cycling, and oxidative phosphorylation in the liver of dairy cows with intensive body fat mobilization during early lactation.  

PubMed

The onset of milk production lets mammals experience an enormous energy and nutrient demand. To meet these requirements, high-yielding dairy cows mobilize body fat resulting in an augmented hepatic oxidative metabolism, which has been suggested to signal for depressing hunger after calving. To examine how the extent of fat mobilization influences hepatic oxidative metabolism and thus potentially feed intake, blood and liver samples of 19 Holstein cows were taken throughout the periparturient period. Retrospectively grouped according to high (H) and low (L) liver fat content, H cows showed higher fatty acid but lower amino acid plasma concentrations and lower feed intake than L cows. The hepatic phospho-AMPK/total AMP ratio was not different between groups but decreased after parturition. A 2-DE coupled MALDI-TOF-TOF analysis and qRT-PCR studies revealed H cows having lower expressions of major enzymes involved in mitochondrial ?-oxidation, urea cycling, and the pentose phosphate pathway but higher expressions of enzymes participating in peroxisomal and endoplasmic fatty acid degradation, pyruvate and TCA cycling, amino acid catabolism, oxidative phosphorylation, and oxidative stress defense. These data indicate that increasing lipolysis leads to augmenting nutrient catabolism for anaplerosis and mitochondrial respiration, providing a molecular link between hepatic oxidative processes and feed intake. PMID:23046364

Schäff, Christine; Börner, Sabina; Hacke, Sandra; Kautzsch, Ulrike; Albrecht, Dirk; Hammon, Harald M; Röntgen, Monika; Kuhla, Björn

2012-11-01

31

Effect of glutamine substitution by TCA cycle intermediates on the production and sialylation of Fc-fusion protein in Chinese hamster ovary cell culture.  

PubMed

In an effort to reduce the accumulation of ammonia in culture medium, three different TCA cycle intermediates, (alpha-ketoglutarate (?-KG), citric acid and succinic acid) along with glutamic acid for a comparison, were examined as a substitute for glutamine with rCHO cell line producing a Fc-fusion glycoprotein. Among them, ?-KG showed the best production performance. When cells were cultivated with 4mM ?-KG, the final ammonia concentration did not exceed 3mM, which is less than one fourth of that with 4mM glutamine. The replacement of glutamine increased the lag phase and reduced cell growth. However, it increased the specific productivity by 2.7-fold, resulting in a 1.3-fold increase in the maximum product concentration. Furthermore, the sialic acid content of the Fc-fusion protein with 4mM ?-KG was higher than that with 4mM glutamine in all cultures, most likely due to the lower ammonia concentration. The results of Western blotting and activity assays of intracellular ?-2,3-sialyltransferase and extracellular sialidases are in good agreement with tests done to assess the sialic acid content of the Fc-fusion protein. Taken together, the data obtained here demonstrate that ?-KG is a potential substitute for glutamine for improved glycoprotein production in rCHO cells. PMID:24721212

Ha, Tae Kwang; Lee, Gyun Min

2014-06-20

32

ATCA/?TCA for physics  

NASA Astrophysics Data System (ADS)

ATCA/?TCA platforms are attractive because of the modern serial link architecture, high availability features and many packaging options. Less-demanding availability applications can be met economically by scaling back speed and redundancy. The ATCA specification was originally targeted for the Telecom industry but has gained recently a much wider user audience. The purpose of this paper is to report on present hardware and software R&D efforts where ATCA and ?TCA are planned, already being used or in development using selected examples for accelerator and detectors in the Physics community. It will present also the status of a proposal for physics extensions to ATCA/?TCA specifications to promote inter-operability of laboratory and industry designs for physics.

Jezynski, Tomasz; Larsen, Raymond; Le Du, Patrick

2010-11-01

33

Tricalcium aluminate hexahydrate (TCA) filter aid in the Bayer industry: factors affecting TCA preparation and morphology  

Microsoft Academic Search

Tricalcium aluminate hexahydrate (TCA) is used within the Bayer industry as a filter aid during purification of sodium aluminate liquors — a role in which the TCA morphology and particle size are particularly important. In spite of this usefulness, no studies have been reported in the open literature examining the influence of reaction variables on the morphology of TCA prepared

B. I. Whittington; T. M. Fallows; M. J. Willing

1997-01-01

34

Knockdown of Cdc6 inhibits proliferation of tongue squamous cell carcinoma Tca8113 cells.  

PubMed

The present study aimed at evaluating the effects of Cdc6 downregulation on the proliferation of Tca8113 cells. Two lentiviral vectors (KD1 and KD2) expression cdc6 siRNA were constructed and then infected into Tca8113 cells. Real-time PCR and Western blot analysis were performed to detect the mRNA and protein expression of Cdc6. MTT assays were employed to delineate the growth curves, and flow cytometry was performed to assess cell-cycle progression and apoptosis in Tca8113 cells. Following infection with the lentiviral vectors, real-time PCR and Western blot analysis revealed that Cdc6 expression was markedly suppressed in Tca8113 cells. When compared with the negative control group, the mRNA expression of Cdc6 was reduced by 50% and 65% and the protein expression by 65.87% and 79.38% in cells harboring KD1 or KD2, respectively. Cell growth was slowed, and the growth inhibition rate was 25.84% and 30.34% in Tca8113 cells following infection with KD1 or KD2, respectively. In addition, cell-cycle progression was altered. In KD- infected Tca8113 cells, the proportion of cells in the S phase was markedly reduced, but the proportion in the G1 phase was significantly increased; this was accompanied by an increase in cell apoptosis. Downregulation of Cdc6 effectively inhibited the proliferation of Tca8113 cells. PMID:22974333

Feng, Chong-Jin; Lu, Xiao-Wei; Luo, Dong-Yuan; Li, Hui-Jun; Guo, Jun-Bing

2013-04-01

35

PIE Nacelle Flow Analysis and TCA Inlet Flow Quality Assessment  

NASA Technical Reports Server (NTRS)

This presentation includes three topics: (1) Analysis of isolated boattail drag; (2) Computation of Technology Concept Airplane (TCA)-installed nacelle effects on aerodynamic performance; and (3) Assessment of TCA inlet flow quality.

Shieh, C. F.; Arslan, Alan; Sundaran, P.; Kim, Suk; Won, Mark J.

1999-01-01

36

Components and Cycles of a Random Function.  

National Technical Information Service (NTIS)

This investigation examines the average distribution of the components and cycles of a random function. Here we refer to the mappings from a finite set of, say, n elements into itself; denoted by GAMMA/sub n/. Suppose the elements of GAMMA/sub n/ are assi...

J. M. DeLaurentis

1987-01-01

37

Optimization of Antennae for Alfven Wave Heating in the TCA Tokamak.  

National Technical Information Service (NTIS)

A one-dimensioanl cylindrical model including Hall current effects is used to optimize the antenna system for Alfven wave heating in the TCA tokamak. The power absorbed in the plasma is computed as a function of the shape of the antenna, its orientation w...

F. Hofmann K. Appert L. Villard

1984-01-01

38

Unstructured Navier-Stokes Analysis of Full TCA Configuration  

NASA Technical Reports Server (NTRS)

This paper presents an Unstructured Navier-Stokes Analysis of Full TCA (Technology Concept Airplane) Configuration. The topics include: 1) Motivation; 2) Milestone and approach; 3) Overview of the unstructured-grid system; 4) Results on full TCA W/B/N/D/E configuration; 5) Concluding remarks; and 6) Future directions.

Frink, Neal T.; Pirzadeh, Shahyar Z.

1999-01-01

39

In folio respiratory fluxomics revealed by 13C isotopic labeling and H/D isotope effects highlight the noncyclic nature of the tricarboxylic acid "cycle" in illuminated leaves.  

PubMed

While the possible importance of the tricarboxylic acid (TCA) cycle reactions for leaf photosynthesis operation has been recognized, many uncertainties remain on whether TCA cycle biochemistry is similar in the light compared with the dark. It is widely accepted that leaf day respiration and the metabolic commitment to TCA decarboxylation are down-regulated in illuminated leaves. However, the metabolic basis (i.e. the limiting steps involved in such a down-regulation) is not well known. Here, we investigated the in vivo metabolic fluxes of individual reactions of the TCA cycle by developing two isotopic methods, (13)C tracing and fluxomics and the use of H/D isotope effects, with Xanthium strumarium leaves. We provide evidence that the TCA "cycle" does not work in the forward direction like a proper cycle but, rather, operates in both the reverse and forward directions to produce fumarate and glutamate, respectively. Such a functional division of the cycle plausibly reflects the compromise between two contrasted forces: (1) the feedback inhibition by NADH and ATP on TCA enzymes in the light, and (2) the need to provide pH-buffering organic acids and carbon skeletons for nitrate absorption and assimilation. PMID:19675152

Tcherkez, Guillaume; Mahé, Aline; Gauthier, Paul; Mauve, Caroline; Gout, Elizabeth; Bligny, Richard; Cornic, Gabriel; Hodges, Michael

2009-10-01

40

In Folio Respiratory Fluxomics Revealed by 13C Isotopic Labeling and H/D Isotope Effects Highlight the Noncyclic Nature of the Tricarboxylic Acid "Cycle" in Illuminated Leaves1[W  

PubMed Central

While the possible importance of the tricarboxylic acid (TCA) cycle reactions for leaf photosynthesis operation has been recognized, many uncertainties remain on whether TCA cycle biochemistry is similar in the light compared with the dark. It is widely accepted that leaf day respiration and the metabolic commitment to TCA decarboxylation are down-regulated in illuminated leaves. However, the metabolic basis (i.e. the limiting steps involved in such a down-regulation) is not well known. Here, we investigated the in vivo metabolic fluxes of individual reactions of the TCA cycle by developing two isotopic methods, 13C tracing and fluxomics and the use of H/D isotope effects, with Xanthium strumarium leaves. We provide evidence that the TCAcycle” does not work in the forward direction like a proper cycle but, rather, operates in both the reverse and forward directions to produce fumarate and glutamate, respectively. Such a functional division of the cycle plausibly reflects the compromise between two contrasted forces: (1) the feedback inhibition by NADH and ATP on TCA enzymes in the light, and (2) the need to provide pH-buffering organic acids and carbon skeletons for nitrate absorption and assimilation.

Tcherkez, Guillaume; Mahe, Aline; Gauthier, Paul; Mauve, Caroline; Gout, Elizabeth; Bligny, Richard; Cornic, Gabriel; Hodges, Michael

2009-01-01

41

Effect of siRNA-mediated downregulation of VEGF in Tca8113 cells on the activity of monocyte-derived dendritic cells.  

PubMed

Vascular endothelial growth factor (VEGF) is a tumor angiogenesis factor that is important in immune regulation. In our previous study, we found that VEGF expression in the peripheral blood and neoplasm nest from patients with oral squamous cell carcinoma (OSCC) was positively correlated with the course of disease, while an inverse correlation between VEGF expression and dendritic cells (DCs) was identified in the peripheral blood. Therefore, in the present study, we investigated whether inhibition of human VEGF in the human tongue carcinoma cell line Tca8113 had effects on the activity of monocyte-derived DCs. We knocked down the expression of human VEGF in Tca8113 cells using the small interfering RNA (siRNA) technique. Tca8113 cells pre-transfected with siRNA targeting VEGF were co-cultured with monocyte?derived immature and mature DCs. Cell proliferation was evaluated by a WST-8 assay. Cell apoptosis, cell cycle and cell phenotypes were determined by flow cytometry. The data revealed that downregulation of the human VEGF significantly inhibited the proliferation of Tca8113 cells and increased apoptosis. Inhibition of human VEGF arrested the cell cycle of Tca8113 cells at the G0/G1 phase. Our results showed that the co-culture of DCs with Tca8113 cells markedly inhibited the expression of the mature markers of DCs including HLA-DR, CD80, CD86, CD40 and CD1a, as well as the immature marker CD83, while inhibition of human VEGF in Tca8113 cells significantly reversed these effects. Therefore, human VEGF in Tca8113 cells may not only regulate the cell proliferation and apoptosis of oral squamous cell carcinoma cells, but may also inhibit DC maturation. PMID:22741012

Ni, Yan-Hong; Wang, Zhi-Yong; Huang, Xiao-Feng; Shi, Pei-Hua; Han, Wei; Hou, Ya-Yi; Hua, Zi-Chun; Hu, And Qin-Gang

2012-04-01

42

TCA1, a single nuclear-encoded translational activator specific for petA mRNA in Chlamydomonas reinhardtii chloroplast.  

PubMed Central

We isolated seven allelic nuclear mutants of Chlamydomonas reinhardtii specifically blocked in the translation of cytochrome f, a major chloroplast-encoded subunit of the photosynthetic electron transport chain encoded by the petA gene. We recovered one chloroplast suppressor in which the coding region of petA was now expressed under the control of a duplicated 5' untranslated region from another open reading frame of presently unknown function. Since we also recovered 14 nuclear intragenic suppressors, we ended up with 21 alleles of a single nuclear gene we called TCA1 for translation of cytochrome b(6)f complex petA mRNA. The high number of TCA1 alleles, together with the absence of genetic evidence for other nuclear loci controlling translation of the chloroplast petA gene, strongly suggests that TCA1 is the only trans-acting factor. We studied the assembly-dependent regulation of cytochrome f translation--known as the CES process--in TCA1-mutated contexts. In the presence of a leaky tca1 allele, we observed that the regulation of cytochrome f translation was now exerted within the limits of the restricted translational activation conferred by the altered version of TCA1 as predicted if TCA1 was the ternary effector involved in the CES process.

Wostrikoff, K; Choquet, Y; Wollman, F A; Girard-Bascou, J

2001-01-01

43

Functional interplay between cell cycle and cell phenotypes  

PubMed Central

Cell cycle distribution of adherent cells is typically assessed using flow cytometry, which precludes the measurements of many cell properties and their cycle phase in the same environment. Here we develop and validate a microscopy system to quantitatively analyze the cell-cycle phase of thousands of adherent cells and their associated cell properties simultaneously. This assay demonstrates that population-averaged cell phenotypes can be written as a linear combination of cell-cycle fractions and phase-dependent phenotypes. By perturbing cell cycle through inhibition of cell-cycle regulators or changing nuclear morphology by depletion of structural proteins, our results reveal that cell cycle regulators and structural proteins can significantly interfere with each other’s prima facie functions. This study introduces a high-throughput method to simultaneously measure cell cycle and phenotypes at single-cell resolution, which reveals a complex functional interplay between cell cycle and cell phenotypes.

Chen, Wei-Chiang; Wu, Pei-Hsun; Phillip, Jude M.; Khatau, Shyam B.; Choi, Jae Min; Dallas, Matthew R.; Konstantopoulos, Konstantinos; Sun, Sean X.; Lee, Jerry S.H.; Hodzic, Didier; Wirtz, Denis

2013-01-01

44

Functional interplay between the cell cycle and cell phenotypes.  

PubMed

Cell cycle distribution of adherent cells is typically assessed using flow cytometry, which precludes the measurements of many cell properties and their cycle phase in the same environment. Here we develop and validate a microscopy system to quantitatively analyze the cell-cycle phase of thousands of adherent cells and their associated cell properties simultaneously. This assay demonstrates that population-averaged cell phenotypes can be written as a linear combination of cell-cycle fractions and phase-dependent phenotypes. By perturbing the cell cycle through inhibition of cell-cycle regulators or changing nuclear morphology by depletion of structural proteins, our results reveal that cell cycle regulators and structural proteins can significantly interfere with each other's prima facie functions. This study introduces a high-throughput method to simultaneously measure the cell cycle and phenotypes at single-cell resolution, which reveals a complex functional interplay between the cell cycle and cell phenotypes. PMID:23319145

Chen, Wei-Chiang; Wu, Pei-Hsun; Phillip, Jude M; Khatau, Shyam B; Choi, Jae Min; Dallas, Matthew R; Konstantopoulos, Konstantinos; Sun, Sean X; Lee, Jerry S H; Hodzic, Didier; Wirtz, Denis

2013-03-01

45

Preliminary Evaluation of Nonlinear Effects on TCA Flutter  

NASA Technical Reports Server (NTRS)

The objective of this study is to investigate the effect of nonlinear aerodynamics, especially at high angles-of-attack with leading-edge separation, on the TCA flutter properties at transonic speeds. In order to achieve that objective, flutter simulations with Navier-Stokes CFD must be performed. To this end, time-marching Navier-Stokes solutions are computed for the TCA wing/body configuration at high angles-of-attack in transonic flight regimes. The approach is to perform non-linear flutter calculations on the TCA at two angles-of-attack, the first one being a case with attached flow (a=2.8 degrees) and the second one being a high angle-of-attack case with a wing leading edge vortex (a=12.11 degrees). Comparisons of the resulting histories and frequency damping information for both angles-of-attack will evaluate the impact of high-alpha aerodynamics on flutter.

Arslan, Alan E.; Hartwich, Peter M.; Baker, Myles L.

1998-01-01

46

Citric acid cycle and role of its intermediates in metabolism.  

PubMed

The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. It is the most important metabolic pathway for the energy supply to the body. TCA is the most important central pathway connecting almost all the individual metabolic pathways. In this review article, introduction, regulation and energetics of TCA cycle have been discussed. The present study was carried out to review literature on TCA cycle. PMID:24068518

Akram, Muhammad

2014-04-01

47

Interpreting functional imaging studies in terms of neurotransmitter cycling  

PubMed Central

Functional imaging experiments, in particular positron-emission tomography and functional magnetic resonance imaging, can be analyzed either in psychological terms or on the basis of neuroscience. In the usual psychological interpretation, stimulations are designed to activate specific mental processes identified by cognitive psychology, which are then localized by the signals in functional imaging experiments. An alternate approach would be to analyze experiments in terms of the neurobiological processes responsible for the signals. Recent in vivo 13C NMR measurements of the glutamate-to-glutamine neurotransmitter cycling in rat and human brains facilitate a neuroscientific interpretation of functional imaging data in terms of neurobiological processes since incremental neurotransmitter flux showed a 1:1 stoichiometry with the incremental rate of glucose oxidation. Because functional imaging signals depend on brain energy consumption, a quantitative relationship can be established between the signal (S) and the specific neurochemical cerebral neurotransmitter activity (N) of glutamate-to-glutamine neurotransmitter cycling. The quantitation of neuronal activity proposed has implications for the psychological design and interpretation of functional imaging experiments. Measurements of the neurotransmitter cycling flux at rest in functional imaging experiments suggest that performing cognitive tasks and sensory stimulations increases neurotransmitter cycling by only 10–20%. Therefore it cannot be assumed that reference state activities are negligible, nor that they are constant during stimulation.

Shulman, Robert G.; Rothman, Douglas L.

1998-01-01

48

Proteomic analysis of protein expression profiles during hyperthermia-induced apoptosis in Tca8113 cells  

PubMed Central

The aim of the present study was to explore protein expression profiles during cancer cell apoptosis induced by hyperthermia. A hyperthermia-induced apoptosis model was established using a Tca8113 cell line derived from a human tongue squamous cell carcinoma, which underwent fluorescent differential display two-dimensional (2D) gel electrophoresis at 2, 6, 8, 12 and 24 h following the induction of hyperthermia. Proteins were identified by mass spectrometry analysis. Expression changes in the proteins were detected by western blot analysis. A total of 107 proteins were detected that exhibited different expression levels in the hyperthermia-treated cells compared with the controls, and 57 of these proteins were identified. Expression changes in the representative proteins were further verified by western blot analysis. These 57 proteins were identified according to the following functional groups: energy metabolism-related enzymes, cytoskeleton-related proteins, chaperones, transcription factors, protein synthesis-related proteins and cell division- and proliferation-related proteins. These groups included 44 upregulated and 13 downregulated proteins. Among the 44 upregulated proteins, 27 were upregulated continuously, eight were upregulated at an early time-point and nine were upregulated at a middle to late time-point. Among the 13 downregulated proteins, five were downregulated continuously, six were downregulated at an early time-point and two were downregulated at a middle to late time-point. These results indicate that hyperthermia-induced Tca8113 cell apoptosis is controlled by multiple factors, which include time and regulatory proteins.

JIANG, WEN; BIAN, LI; WANG, NING; HE, YONGWEN

2013-01-01

49

Does prolonged cycling of moderate intensity affect immune cell function?  

PubMed Central

Background: Prolonged exercise may induce temporary immunosuppression with a presumed increased susceptibility for infection. However, there are only few data on immune cell function after prolonged cycling at moderate intensities typical for road cycling training sessions. Methods: The present study examined the influence on immune cell function of 4 h of cycling at a constant intensity of 70% of the individual anaerobic threshold. Interleukin-6 (IL-6) and C-reactive protein (CRP), leukocyte and lymphocyte populations, activities of natural killer (NK), neutrophils, and monocytes were examined before and after exercise, and also on a control day without exercise. Results: Cycling for 4 h induced a moderate acute phase response with increases in IL-6 from 1.0 (SD 0.5) before to 9.6 (5.6) pg/ml 1 h after exercise and CRP from 0.5 (SD 0.4) before to 1.8 (1.3) mg/l 1 day after exercise. Although absolute numbers of circulating NK cells, monocytes, and neutrophils increased during exercise, on a per cell basis NK cell activity, neutrophil and monocyte phagocytosis, and monocyte oxidative burst did not significantly change after exercise. However, a minor effect over time for neutrophil oxidative burst was noted, tending to decrease after exercise. Conclusions: Prolonged cycling at moderate intensities does not seem to seriously alter the function of cells of the first line of defence. Therefore, the influence of a single typical road cycling training session on the immune system is only moderate and appears to be safe from an immunological point of view.

Scharhag, J; Meyer, T; Gabriel, H; Schlick, B; Faude, O; Kindermann, W; Shephard, R

2005-01-01

50

Prolactin secretion and ovarian function in cycling and non-cycling African female elephants (Loxodonta africana).  

PubMed

Reproduction of captive elephants in zoos has shown a low fecundity and requires improvement. One of the reasons for low fecundity is ovarian dysfunction in many female elephants. To investigate whether prolactin has a correlation with ovarian function in female elephants, the serum concentrations of prolactin, progesterone and estradiol-17beta in four African female elephants (one cycling female and three non-cycling female elephants) were measured. Cyclic patterns of prolactin and estradiol-17beta were observed in the cycling female elephant, which tended to be high during the follicular phase and low during the luteal phase. On the other hand, a cyclic pattern of prolactin was not observed in the non-cycling female elephants. One of the three non-cycling females (Mako) had developed breasts and showed significantly higher average levels of prolactin than the other female elephants. These results suggested that high concentrations of circulating estradiol-17beta during the follicular phase stimulated prolactin secretion. They also suggested that hyperprolactinemia in Mako was one of the causes of the developed mammary glands and ovarian dysfunction. PMID:20179385

Yamamoto, Yuki; Yamamoto, Tatsuya; Watanabe, Gen; Yuto, Natsuki; Keio, Megumi; Narushima, Etsuo; Katayanagi, Masayuki; Nakao, Risa; Morikubo, Syu; Sakurai, Yuko; Kaneko, Mikako; Kaewmanee, Saroch; Taya, Kazuyoshi

2010-07-01

51

An EMG Feedback Control Functional Electrical Stimulation Cycling System  

Microsoft Academic Search

The prevalence of stroke and its residual disability is getting higher and higher in the whole world population. The functional\\u000a electrical stimulation cycling system (FES-CS) is useful for hemiplegic patients to make the muscles of stroke patients be\\u000a under hybrid activation. The raw electromyography (EMG) takes down the residual muscle force of stroke subjects; and the peak-to-peak\\u000a of stimulus EMG

Chien-Chih Chen; Zong-Cian He; Ya-Hsin Hsueh

2011-01-01

52

Preliminary Results of the 1.5% TCA (Modular) Controls Model in the NASA Langley UPWT  

NASA Technical Reports Server (NTRS)

To summarize the significant highlights in this report: (1) Data quality, determined by multiple repeat runs performed on the TCA baseline configuration, and long-term repeatability, determined by comparing baseline Reference H data from this test to a previous test, have been shown to be good. (2) The longitudinal stability of the TCA is more non-linear than for the Reference H, and while it is similar at normal lift values, the TCA has considerably more pitch-up at higher lift. (3) Longitudinal control effectiveness of the TCA is similar to the Reference H and the ratio of elevator effectiveness to horizontal tail effectiveness is approximately 0.3. (4) The directional stability of the TCA is improved relative to Reference H at higher angles-of attack. The chine is effective for improving directional stability.

Kubiatko, Paul; McMillin, Naomi; Cameron, Douglas C.

1999-01-01

53

Biological catalysis of the hydrological cycle: life's thermodynamic function  

NASA Astrophysics Data System (ADS)

Darwinian theory depicts life as being overwhelmingly consumed by a fight for survival in a hostile environment. However, from a thermodynamic perspective, life is a dynamic out of equilibrium process, stabilizing and coevolving in concert with its abiotic environment. The living component of the biosphere on the surface of the Earth of greatest biomass, the plants and cyanobacteria, are involved in the transpiration of a vast amount of water. Transpiration is part of the global water cycle, and it is this cycle that distinguishes Earth from its apparently life barren neighboring planets, Venus and Mars. The dissipation of sunlight into heat by organic molecules in the biosphere and its coupling to the water cycle (as well as other abiotic processes), is by far the greatest entropy producing process occurring on Earth. Life, from this perspective, can be viewed as performing an important thermodynamic function; acting as a dynamic catalyst by aiding irreversible abiotic process such as the water cycle, hurricanes, and ocean and wind currents to produce entropy. The role of animals in this view is that of unwitting but dedicated servants of the plants and cyanobacteria, helping them to grow and to spread into initially inhospitable areas.

Michaelian, K.

2011-01-01

54

National Exposure Registry Volatile Organic Compounds Registry 1,1,1-Trichloroethane (TCA) Subregistry Baseline and Followup 1 Technical Report.  

National Technical Information Service (NTIS)

This report describes the baseline activities and results of the statistical analyses of the baseline and first follow-up data for the TCA Subregistry of the Volatile Organic Compounds Registry of the National Exposure Registry. The TCA Subregistry baseli...

J. R. Burg G. L. Gist

1996-01-01

55

IRIS Toxicological Review of Trichloroacetic Acid (TCA) (Interagency Science Discussion Draft)  

EPA Science Inventory

EPA is releasing the draft report, Toxicological Review of Trichloroacetic Acid (TCA), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development ...

56

ANALYSIS AND SIMULATION OF RECYCLE SO2-LIME SLURRY IN TCA (TURBULENT CONTACT ABSORBER) SCRUBBER SYSTEM  

EPA Science Inventory

The report gives results of an analysis of flue gas desulfurization by a turbulent contact absorber (TCA) employing lime slurry, including the development of performance equations for the scrubber-hold tank recycle system. Performance characteristics investigated include pressure...

57

Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell.  

PubMed

An imbalance of plasma amino acids (AA) is observed cirrhotic patients. Here we report that the imbalance suppresses the maturation of dendritic cells (DCs) by reducing the intracellular ATP due to interference with the mitochondrial tricarboxylic acid (TCA) cycle. We used serum-free culture medium consistent with the average concentration of the plasma AA from a healthy volunteer (HCM) and that from patients with advanced cirrhosis (ACM). We compared the function of DCs and the metabolism of glucose-amino acids under each medium. The maturation and intracellular ATP of immature DCs were lower under ACM in spite of the enhancement of mitochondrial respiratory chain complex genes. Metabolomics revealed that the TCA cycle metabolite, fumarate and 2-oxoglutarate were increased in DCs generated under ACM. Consistent with in vitro, In CD1c(+) or CD14(+) cells from cirrhotic patients, the gene expression of 2-oxoglutarate-succinate-fumarate transition enzymes were significantly different from the cells of healthy controls. PMID:24322372

Kakazu, Eiji; Kondo, Yasuteru; Kogure, Takayuki; Ninomiya, Masashi; Kimura, Osamu; Ueno, Yoshiyuki; Shimosegawa, Tooru

2013-01-01

58

Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell  

PubMed Central

An imbalance of plasma amino acids (AA) is observed cirrhotic patients. Here we report that the imbalance suppresses the maturation of dendritic cells (DCs) by reducing the intracellular ATP due to interference with the mitochondrial tricarboxylic acid (TCA) cycle. We used serum-free culture medium consistent with the average concentration of the plasma AA from a healthy volunteer (HCM) and that from patients with advanced cirrhosis (ACM). We compared the function of DCs and the metabolism of glucose-amino acids under each medium. The maturation and intracellular ATP of immature DCs were lower under ACM in spite of the enhancement of mitochondrial respiratory chain complex genes. Metabolomics revealed that the TCA cycle metabolite, fumarate and 2-oxoglutarate were increased in DCs generated under ACM. Consistent with in vitro, In CD1c+ or CD14+ cells from cirrhotic patients, the gene expression of 2-oxoglutarate-succinate-fumarate transition enzymes were significantly different from the cells of healthy controls.

Kakazu, Eiji; Kondo, Yasuteru; Kogure, Takayuki; Ninomiya, Masashi; Kimura, Osamu; Ueno, Yoshiyuki; Shimosegawa, Tooru

2013-01-01

59

Metabolic Engineering of the Tricarboxylic Acid Cycle for Improved Lysine Production by Corynebacterium glutamicum?  

PubMed Central

In the present work, lysine production by Corynebacterium glutamicum was improved by metabolic engineering of the tricarboxylic acid (TCA) cycle. The 70% decreased activity of isocitrate dehydrogenase, achieved by start codon exchange, resulted in a >40% improved lysine production. By flux analysis, this could be correlated to a flux shift from the TCA cycle toward anaplerotic carboxylation.

Becker, Judith; Klopprogge, Corinna; Schroder, Hartwig; Wittmann, Christoph

2009-01-01

60

Alternative Functions of Core Cell Cycle Regulators in Neuronal Migration, Neuronal Maturation, and Synaptic Plasticity  

Microsoft Academic Search

Recent studies have demonstrated that boundaries separating a cycling cell from a postmitotic neuron are not as concrete as expected. Novel and unique physiological functions in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. These ''core'' cell cycle regulators serve diverse postmitotic functions that span various developmental stages of a neuron, including neuronal migration,

Christopher L. Frank; Li-Huei Tsai

2009-01-01

61

TcaR-ssDNA complex crystal structure reveals new DNA binding mechanism of the MarR family proteins  

PubMed Central

The teicoplanin-associated locus regulator (TcaR) regulates gene expression of proteins on the intercellular adhesion (ica) locus involved in staphylococci poly-N-acetylglucosamine biosynthesis. The absence of TcaR increases poly-N-acetylglucosamine production and promotes biofilm formation. Until recently, the mechanism of multiple antibiotic resistance regulator family protein members, such as TcaR, was restricted to binding double-stranded DNA. However, we recently found that TcaR strongly interacts with single-stranded DNA, which is a new role for this family of proteins. In this study, we report Staphylococcus epidermidis TcaR–single-stranded DNA complex structures. Our model suggests that TcaR and single-stranded DNA form a 61-symmetry polymer composed of TcaR dimers with single-stranded DNA that wraps outside the polymer and 12 nt per TcaR dimer. Single-stranded DNA binding to TcaR involves a large conformational change at the DNA binding lobe. Several point mutations involving the single-stranded DNA binding surface validate interactions between single-stranded DNA and TcaR. Our results extend the novel role of multiple antibiotic resistance regulator family proteins in staphylococci.

Chang, Yu-Ming; Ho, Chun-Han; Chen, Cammy K.-M.; Maestre-Reyna, Manuel; Chang-Chien, Masatoshi Weiting; Wang, Andrew H.-J.

2014-01-01

62

Molecular evolution of SRP cycle components: functional implications.  

PubMed Central

Signal recognition particle (SRP) is a cytoplasmic ribonucleoprotein that targets a subset of nascent presecretory proteins to the endoplasmic reticulum membrane. We have considered the SRP cycle from the perspective of molecular evolution, using recently determined sequences of genes or cDNAs encoding homologs of SRP (7SL) RNA, the Srp54 protein (Srp54p), and the alpha subunit of the SRP receptor (SR alpha) from a broad spectrum of organisms, together with the remaining five polypeptides of mammalian SRP. Our analysis provides insight into the significance of structural variation in SRP RNA and identifies novel conserved motifs in protein components of this pathway. The lack of congruence between an established phylogenetic tree and size variation in 7SL homologs implies the occurrence of several independent events that eliminated more than half the sequence content of this RNA during bacterial evolution. The apparently non-essential structures are domain I, a tRNA-like element that is constant in archaea, varies in size among eucaryotes, and is generally missing in bacteria, and domain III, a tightly base-paired hairpin that is present in all eucaryotic and archeal SRP RNAs but is invariably absent in bacteria. Based on both structural and functional considerations, we propose that the conserved core of SRP consists minimally of the 54 kDa signal sequence-binding protein complexed with the loosely base-paired domain IV helix of SRP RNA, and is also likely to contain a homolog of the Srp68 protein. Comparative sequence analysis of the methionine-rich M domains from a diverse array of Srp54p homologs reveals an extended region of amino acid identity that resembles a recently identified RNA recognition motif. Multiple sequence alignment of the G domains of Srp54p and SR alpha homologs indicates that these two polypeptides exhibit significant similarity even outside the four GTPase consensus motifs, including a block of nine contiguous amino acids in a location analogous to the binding site of the guanine nucleotide dissociation stimulator (GDS) for E. coli EF-Tu. The conservation of this sequence, in combination with the results of earlier genetic and biochemical studies of the SRP cycle, leads us to hypothesize that a component of the Srp68/72p heterodimer serves as the GDS for both Srp54p and SR alpha. Using an iterative alignment procedure, we demonstrate similarity between Srp68p and sequence motifs conserved among GDS proteins for small Ras-related GTPases. The conservation of SRP cycle components in organisms from all three major branches of the phylogenetic tree suggests that this pathway for protein export is of ancient evolutionary origin. Images

Althoff, S; Selinger, D; Wise, J A

1994-01-01

63

Functional anatomy of the sleep-wakefulness cycle: wakefulness.  

PubMed

Sleep is a necessary, diverse, periodic, and an active condition circadian and homeostatically regulated and precisely meshed with waking time into the sleep-wakefulness cycle (SWC). Photic retinal stimulation modulates the suprachiasmatic nucleus, which acts as the pacemaker for SWC rhythmicity. Both the light period and social cues adjust the internal clock, making the SWC a circadian, 24-h period in the adult human. Bioelectrical and behavioral parameters characterize the different phases of the SWC. For a long time, lesions and electrical stimulation of brain structures, as well as connection studies, were the main methods used to decipher the foundations of the functional anatomy of the SWC. That is why the first section of this review presents these early historical studies to then discuss the current state of our knowledge based on our understanding of the functional anatomy of the structures underlying the SWC. Supported by this description, we then present a detailed review and update of the structures involved in the phase of wakefulness (W), including their morphological, functional, and chemical characteristics, as well as their anatomical connections. The structures for W generation are known as the "ascending reticular activating system", and they keep and maintain the "thalamo-cerebral cortex unit" awake. This system originates from the neuronal groups located within the brainstem, hypothalamus, and basal forebrain, which use known neurotransmitters and whose neurons are more active during W than during the other SWC states. Thus, synergies among several of these neurotransmitters are necessary to generate the cortical and thalamic activation that is characteristic of the W state, with all the plastic qualities and nuances present in its different behavioral circumstances. Each one of the neurotransmitters exerts powerful influences on the information and cognitive processes as well as attentional, emotional, motivational, behavioral, and arousal states. The awake "thalamo-cerebral cortex unit" controls and adjusts the activation pattern through a top-down action on the subcortical cellular groups that are the origin of the "ascending reticular activating system". PMID:21166301

Reinoso-Suárez, Fernando; de Andrés, Isabel; Garzón, Miguel

2011-01-01

64

MicroTCA-based Global Trigger Upgrade project for the CMS experiment at LHC  

NASA Astrophysics Data System (ADS)

The electronics of the first Level Global Trigger (GT) of CMS is the last stage of the Level-1 trigger system [1]. At LHC up to 40 million collisions of proton bunches occur every second, resulting in about 800 million proton collisions. The CMS Level-1 Global Trigger [1], a custom designed electronics system based on FPGA technology and the VMEbus system, performs a quick on-line analysis of each collision every 25 ns and decides whether to reject or to accept it for further analysis. The CMS trigger group of the Institute of High Energy Physics in Vienna (HEPHY) is involved in the Level-1 trigger of the CMS experiment at CERN. As part of the Trigger Upgrade, the Level-1 Global Trigger will be redesigned and implemented in MicroTCA based technology, which allows engineers to detect all possible faults on plug-in boards, in the power supply and in the cooling system. The upgraded Global Trigger will be designed to have the same basic categories of functions as the present GT, but will have more algorithms and more possibilities for combining trigger candidates. Additionally, reconfigurability and testability will be supported based on the next system generation.

Rahbaran, B.; Arnold, B.; Bergauer, H.; Eichberger, M.; Rabady, D.

2011-12-01

65

Differences in Phenotype and Cell Replicative Behavior of Hepatic Tumors Induced by Dichloroacetate (DCA) and Trichloroacetate (TCA)  

Microsoft Academic Search

Dichloroacetate (DCA) and trichloroacetate (TCA) are two hepatocarcinogenic by-products of water chlorination. To compare the effects of DCA and TCA on cell replication in the nodules and tumors they induce, male B6C3F1 mice were administered 2.0 g\\/L DCA or TCA in their drinking water for 38 or 50 weeks, respectively. The pretreated mice were then given water containing 0, 0.02,

Anja J Stauber; Richard J Bull

1997-01-01

66

Comparative study of 15% TCA peel versus 35% glycolic acid peel for the treatment of melasma  

PubMed Central

Background: Chemical peels are the mainstay of a cosmetic practitioner's armamentarium because they can be used to treat some skin disorders and can provide aesthetic benefit. Objectives: To compare 15% TCA peel and 35% glycolic acid peel for the treatment of melasma. Material and Methods: We selected 30 participants of melasma aged between 20 and 50 years from the dermatology outpatient department and treated equal numbers with 15% TCA and 35% glycolic acid. Results: Subjective response as graded by the patient showed good or very good response in 70% participants in the glycolic acid group and 64% in the TCA group. Conclusions: There was statistically insignificant difference in the efficacy between the two groups for the treatment of melasma.

Puri, Neerja

2012-01-01

67

Muscle function during brief maximal exercise: accurate measurements on a friction-loaded cycle ergometer  

Microsoft Academic Search

A friction loaded cycle ergometer was instrumented with a strain gauge and an incremental encoder to obtain accurate measurement of human mechanical work output during the acceleration phase of a cycling sprint. This device was used to characterise muscle function in a group of 15 well-trained male subjects, asked to perform six short maximal sprints on the cycle against a

Laurent M. Arsac; Alain Belli; Jean-René Lacour

1996-01-01

68

Evidence for Autotrophy via the Reverse Tricarboxylic Acid Cycle in the Marine Magnetotactic Coccus Strain MC-1  

PubMed Central

Strain MC-1 is a marine, microaerophilic, magnetite-producing, magnetotactic coccus phylogenetically affiliated with the ?-Proteobacteria. Strain MC-1 grew chemolithotrophically with sulfide and thiosulfate as electron donors with HCO3?/CO2 as the sole carbon source. Experiments with cells grown microaerobically in liquid with thiosulfate and H14CO3?/14CO2 showed that all cell carbon was derived from H14CO3?/14CO2 and therefore that MC-1 is capable of chemolithoautotrophy. Cell extracts did not exhibit ribulose-1,5-bisphosphate carboxylase-oxygenase (RubisCO) activity, nor were RubisCO genes found in the draft genome of MC-1. Thus, unlike other chemolithoautotrophic, magnetotactic bacteria, strain MC-1 does not appear to utilize the Calvin-Benson-Bassham cycle for autotrophy. Cell extracts did not exhibit carbon monoxide dehydrogenase activity, indicating that the acetyl-coenzyme A pathway also does not function in strain MC-1. The 13C content of whole cells of MC-1 relative to the 13C content of the inorganic carbon source (??13C) was ?11.4 . Cellular fatty acids showed enrichment of 13C relative to whole cells. Strain MC-1 cell extracts showed activities for several key enzymes of the reverse (reductive) tricarboxylic acid (rTCA) cycle including fumarate reductase, pyruvate:acceptor oxidoreductase and 2-oxoglutarate:acceptor oxidoreductase. Although ATP citrate lyase (another key enzyme of the rTCA cycle) activity was not detected in strain MC-1 using commonly used assays, cell extracts did cleave citrate, and the reaction was dependent upon the presence of ATP and coenzyme A. Thus, we infer the presence of an ATP-dependent citrate-cleaving mechanism. These results are consistent with the operation of the rTCA cycle in MC-1. Strain MC-1 appears to be the first known representative of the ?-Proteobacteria to use the rTCA cycle for autotrophy.

Williams, Timothy J.; Zhang, Chuanlun L.; Scott, James H.; Bazylinski, Dennis A.

2006-01-01

69

IRIS Toxicological Review of Trichloroacetic Acid (TCA) (Interagency Science Consultation Draft)  

EPA Science Inventory

On September 24, 2009, the Toxicological Review of Trichloroacetic Acid (TCA) and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies an...

70

Thermal-coronary-angiography (TCA) for intraoperative evaluation of graft patency in coronary artery bypass surgery  

Microsoft Academic Search

Despite the evolution of surgical techniques, coronary artery bypass graft surgery is complicated by early and late graft failure. While late graft failure is usually due to progression of the underlying disease, early graft failure can be caused by technical mistakes at the level of anastomoses. Thermal Coronary Angiography (TCA) has been developed to detect intraoperative graft failures. The method

V. Falk; H. Kitzinger; T. Walther; T. Rauch; A. Diegeler; F. W. Mohr

2000-01-01

71

Resistance to vanadium in Pseudomonas fluorescens ATCC 17400 caused by mutations in TCA cycle enzymes.  

PubMed

Vanadium inhibits the growth of Pseudomonas fluorescens ATCC 17400 in the low-iron casamino acids medium and even more when iron is added to the medium. Analysis of transposon mutants allowed the isolation of two mutants with increased resistance to vanadium. One mutant had an insertion in the idh gene coding for the tricarboxylic acid enzyme isocitrate dehydrogenase. The second mutant had the transposon inserted into acnD, one out of three genes coding for a 2-methyl-isocitrate dehydratase (aconitase). In this mutant, there was a higher level of acnB aconitase transcripts while the levels of acnA transcripts were unchanged. A nonpolar idh mutant was obtained, which showed the same level of resistance against vanadium as the original transposon mutant. PMID:17020548

Denayer, Sarah; Matthijs, Sandra; Cornelis, Pierre

2006-11-01

72

Functional models of electrochromic devices: cycling capacity and degradation  

Microsoft Academic Search

Electrical transfer and diffusion of ions and the irreversibility of ion and electron processes in heterojunctions are responsible for degradation of ionic devices. These processes for electrochromic devices (ECD) determine the cycling capacity and lifetime. The basic problem here is how to match the electrochemical parameters (including chemical potential) of heterojunction. The experiments had been carried out on ECD based

Andrejs R. Lusis

1997-01-01

73

Functional models of electrochromic devices: cycling capacity and degradation  

NASA Astrophysics Data System (ADS)

Electrical transfer and diffusion of ions and the irreversibility of ion and electron processes in heterojunctions are responsible for degradation of ionic devices. These processes for electrochromic devices (ECD) determine the cycling capacity and lifetime. The basic problem here is how to match the electrochemical parameters (including chemical potential) of heterojunction. The experiments had been carried out on ECD based on system: (phi) --(phi) , where AAH is solid electrolyte based on antimony acid hydrates. The cycling capacity and degradation processes of ECD are investigated by electro-optical and electro-chemical spectroscopy. The analysis of experimental data are based on assumption that electrode reactions changed composition of electrode and electrolyte materials and surface layers as well as constitution of heterojunction's interface. The conclusions of these investigations and problem analyses are some considerations about electrochemical battery model and cycling capacity of ECD. That depends on reversibility of solid state reactions on the electrode and ion insertion processes and phase stability of electrode and electrolyte materials. The ions of sublattices of immobile ions of solid phases and other components of these phases have to be stable against chemical interactions, diffusion and transfer of mobile ion during cycling.

Lusis, Andrejs R.

1997-02-01

74

Alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity  

PubMed Central

Recent studies have demonstrated that boundaries separating a cycling cell from a post-mitotic neuron are not as concrete as expected. Novel and unique physiological functions in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. These “core” cell cycle regulators serve diverse post-mitotic functions that span various developmental stages of a neuron, including neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis, and synaptic maturation and plasticity. In this review, we detail the non-proliferative post-mitotic roles that these cell cycle proteins have recently been reported to play, the significance of their expression in neurons, mechanistic insight when available, and future prospects.

Frank, Christopher L.; Tsai, Li-Huei

2009-01-01

75

Alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity.  

PubMed

Recent studies have demonstrated that boundaries separating a cycling cell from a postmitotic neuron are not as concrete as expected. Novel and unique physiological functions in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. These "core" cell cycle regulators serve diverse postmitotic functions that span various developmental stages of a neuron, including neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis, and synaptic maturation and plasticity. In this review, we detail the nonproliferative postmitotic roles that these cell cycle proteins have recently been reported to play, the significance of their expression in neurons, mechanistic insight when available, and future prospects. PMID:19447088

Frank, Christopher L; Tsai, Li-Huei

2009-05-14

76

Cycles  

NSDL National Science Digital Library

Just about anywhere you look in the natural sciences you'll find a cycle of some description. From cells to individuals to populations and beyond, cyclical patterns exist on every scale. The following collection of Web sites follows on this theme: The first site (1) is an excellent, animated introduction to the cell cycle from Cells Alive! Users can also get a closer look at the stages of mitosis by following the links provided. The next site from the Center for Biological Timing contains a tutorial on chronobiology, the study of biological rhythms (2). Visitors will find a thorough overview of the human clock and related concepts, with emphasis on our 24-hour sleep-wake cycle. Speaking of internal cycles, the next site contains an interesting article from BBC News, relating how a woman's choice of men may vary in accordance with her menstrual cycle (3). The next site moves from internal to externally-evident cycles, namely the life cycle of the monarch butterfly. Monarch Watch provides a detailed description of the butterfly life cycle, from egg to larva to pupa to adult (4). Perhaps not quite as appealing as the monarch butterfly, but nevertheless intriguing, Schistosoma flatworms have a complicated life cycle involving humans and a particular group of snails. The University of California-Los Angeles Institute of the Environment offers an illustrated explanation of this highly specialized life cycle (5). The following site from Science New Online describes how global climate change is accelerating the annual life cycles of plants and animals around the world (6). On the level of population, the Natural History Museum of Los Angeles County offers the familiar example of the Canada lynx and the hare -- the same example used by countless textbooks to demonstrate the cyclical nature of predator-prey dynamics (7). And finally, Georgia State University provides a nicely simplified introduction to the energy cycle in living things, focusing on the transfer of energy from the sun to plants to animals (8).

Sohmer, Rachel.

77

Yersinia enterocolitica Infection and tcaA-Dependent Killing of Caenorhabditis elegans? †  

PubMed Central

Caenorhabditis elegans is a validated model to study bacterial pathogenicity. We report that Yersinia enterocolitica strains W22703 (biovar 2, serovar O:9) and WA314 (biovar 1B, serovar O:8) kill C. elegans when feeding on the pathogens for at least 15 min before transfer to the feeding strain Escherichia coli OP50. The killing by Yersinia enterocolitica requires viable bacteria and, in contrast to that by Yersinia pestis and Yersinia pseudotuberculosis strains, is biofilm independent. The deletion of tcaA encoding an insecticidal toxin resulted in an OP50-like life span of C. elegans, indicating an essential role of TcaA in the nematocidal activity of Y. enterocolitica. TcaA alone is not sufficient for nematocidal activity because E. coli DH5? overexpressing TcaA did not result in a reduced C. elegans life span. Spatial-temporal analysis of C. elegans infected with green fluorescent protein-labeled Y. enterocolitica strains showed that Y. enterocolitica colonizes the nematode intestine, leading to an extreme expansion of the intestinal lumen. By low-dose infection with W22703 or DH5? followed by transfer to E. coli OP50, proliferation of Y. enterocolitica, but not E. coli, in the intestinal lumen of the nematode was observed. The titer of W22703 cells within the worm increased to over 106 per worm 4 days after infection while a significantly lower number of a tcaA knockout mutant was recovered. A strong expression of tcaA was observed during the first 5 days of infection. Y. enterocolitica WA314 (biovar 1B, serovar O:8) mutant strains lacking the yadA, inv, yopE, and irp1 genes known to be important for virulence in mammals were not attenuated or only slightly attenuated in their toxicity toward the nematode, suggesting that these factors do not play a significant role in the colonization and persistence of this pathogen in nematodes. In summary, this study supports the hypothesis that C. elegans is a natural host and nutrient source of Y. enterocolitica.

Spanier, Britta; Starke, Mandy; Higel, Fabian; Scherer, Siegfried; Fuchs, Thilo M.

2010-01-01

78

Molecular structure and spectral properties of ethyl 3-quinolinecarboxylate (E3Q) and [Ag(E3Q)2(TCA)] complex (TCA=Trichloroacetate).  

PubMed

A new [Ag(E3Q)2(TCA)] complex; (E3Q=Ethyl 3-quinolinecarboxylate and TCA=Trichloroacetate) has been synthesized and characterized using elemental analysis, FTIR, NMR and mass spectroscopy. The molecular geometry and spectroscopic properties of the complex as well as the free ligand have been calculated using the hybrid B3LYP method. The calculations predicted a distorted tetrahedral arrangement around Ag(I) ion. The vibrational spectra of the studied compounds have been assigned using potential energy distribution (PED). TD-DFT method was used to predict the electronic absorption spectra. The most intense absorption band showed a bathochromic shift and lowering of intensity in case of the complex (233.7nm, f=0.5604) compared to E3Q (?max=228.0nm, f=0.9072). The calculated (1)H NMR chemical shifts using GIAO method showed good correlations with the experimental data. The computed dipole moment, polarizability and HOMO-LUMO energy gap were used to predict the nonlinear optical (NLO) properties. It is found that Ag(I) enhances the NLO activity. The natural bond orbital (NBO) analyses were used to elucidate the intramolecular charge transfer interactions causing stabilization for the investigated systems. PMID:24813274

Soliman, Saied M; Kassem, Taher S; Badr, Ahmed M A; Abou Youssef, Morsy A; Assem, Rania

2014-09-15

79

Shortening tobacco life cycle accelerates functional gene identification in genomic research.  

PubMed

Definitive allocation of function requires the introduction of genetic mutations and analysis of their phenotypic consequences. Novel, rapid and convenient techniques or materials are very important and useful to accelerate gene identification in functional genomics research. Here, over-expression of PmFT (Prunus mume), a novel FT orthologue, and PtFT (Populus tremula) lead to shortening of the tobacco life cycle. A series of novel short life cycle stable tobacco lines (30-50 days) were developed through repeated self-crossing selection breeding. Based on the second transformation via a gusA reporter gene, the promoter from BpFULL1 in silver birch (Betula pendula) and the gene (CPC) from Arabidopsis thaliana were effectively tested using short life cycle tobacco lines. Comparative analysis among wild type, short life cycle tobacco and Arabidopsis transformation system verified that it is optional to accelerate functional gene studies by shortening host plant material life cycle, at least in these short life cycle tobacco lines. The results verified that the novel short life cycle transgenic tobacco lines not only combine the advantages of economic nursery requirements and a simple transformation system, but also provide a robust, effective and stable host system to accelerate gene analysis. Thus, shortening tobacco life cycle strategy is feasible to accelerate heterologous or homologous functional gene identification in genomic research. PMID:23107371

Ning, G; Xiao, X; Lv, H; Li, X; Zuo, Y; Bao, M

2012-11-01

80

Fabrication of functionally gradient nanocomposite coatings by plasma electrolytic oxidation based on variable duty cycle  

Microsoft Academic Search

Plasma electrolytic oxidation (PEO) was applied on the surface of commercially pure titanium substrates in a mixed aluminate-phosphate electrolyte in the presence of silicon nitride nanoparticles as suspension in the electrolyte in order to fabricate nanocomposite coatings. Pulsed current was applied based on variable duty cycle in order to synthesize functionally gradient coatings (FGC). Different rates of variable duty cycle

M. Aliofkhazraei; A. Sabour Rouhaghdam

81

Evaluation of Functional Electrical Stimulation to Assist Cycling in Four Adolescents with Spastic Cerebral Palsy  

PubMed Central

Introduction. Adolescents with cerebral palsy (CP) often have difficulty participating in exercise at intensities necessary to improve cardiovascular fitness. Functional electrical stimulation- (FES-) assisted cycling is proposed as a form of exercise for adolescents with CP. The aims of this paper were to adapt methods and assess the feasibility of applying FES cycling technology in adolescents with CP, determine methods of performing cycling tests in adolescents with CP, and evaluate the immediate effects of FES assistance on cycling performance. Materials/Methods. Four participants (12–14 years old; GMFCS levels III-IV) participated in a case-based pilot study of FES-assisted cycling in which bilateral quadriceps muscles were activated using surface electrodes. Cycling cadence, power output, and heart rate were collected. Results. FES-assisted cycling was well tolerated (n = 4) and cases are presented demonstrating increased cadence (2–43?rpm), power output (19–70%), and heart rates (4-5%) and decreased variability (8–13%) in cycling performance when FES was applied, compared to volitional cycling without FES assistance. Some participants (n = 2) required the use of an auxiliary hub motor for assistance. Conclusions. FES-assisted cycling is feasible for individuals with CP and may lead to immediate improvements in cycling performance. Future work will examine the potential for long-term fitness gains using this intervention.

Harrington, Ann Tokay; McRae, Calum G. A.; Lee, Samuel C. K.

2012-01-01

82

Status report on a MicroTCA card for HCAL trigger and readout at SLHC  

NASA Astrophysics Data System (ADS)

We present recent measurements performed using a prototype MicroTCA card for CMS-HCAL Trigger and Readout at SLHC. Our second generation prototype uses a Xilinx XC5VFX70T FPGA to perform the high-speed communication and data processing for up to eight Readout Module fibers that are streaming data at 4.8 Gbps each. The FPGA also uses two SFP+ optical interfaces at 6.4 Gbps each for data transfer to the Trigger System. A local DAQ interface in the FPGA communicates via Gigabit Ethernet with the MicroTCA MCH. Bit Error Rate Test (BERT) results and data integrity analyses are presented in challenging clocking environments including a legacy TTC system. In addition, the status of the IPbus concept for control of deeply embedded devices is presented.

Mans, J.; Frahm, E.

2010-12-01

83

A Novel Function for Cyclin E in Cell Cycle Progression  

Microsoft Academic Search

In this study we demonstrated the presence of a kinase-independent function for cyclin E. Specifically, weobserved that a\\u000a kinase-deficient cyclin E1mutant can reconstitute cyclin E’s function in cyclin E-null cells. Kinase-deficient cyclin E1 is\\u000a loaded onto chromatin during G0 ? S progression, it restores MCM incorporation and it facilitates S phase entry of cyclin\\u000a E-null cells. We also observed that,

Yan Geng; Youngmi Lee; Markus Welcker; Jherek Swanger; Agnieszka Zagozdzon; James M. Roberts; Philipp Kaldis; Bruce E. Clurman; Piotr Sicinski

84

Impact of Polyphenol Antioxidants on Cycling Performance and Cardiovascular Function  

PubMed Central

This investigation sought to determine if supplementation with polyphenol antioxidant (PA) improves exercise performance in the heat (31.5 °C, 55% RH) by altering the cardiovascular and thermoregulatory responses to exercise. Twelve endurance trained athletes ingested PA or placebo (PLAC) for 7 days. Consecutive days of exercise testing were performed at the end of the supplementation periods. Cardiovascular and thermoregulatory measures were made during exercise. Performance, as measured by a 10 min time trial (TT) following 50 min of moderate intensity cycling, was not different between treatments (PLAC: 292 ± 33 W and PA: 279 ± 38 W, p = 0.12). Gross efficiency, blood lactate, maximal neuromuscular power, and ratings of perceived exertion were also not different between treatments. Similarly, performance on the second day of testing, as assessed by time to fatigue at maximal oxygen consumption, was not different between treatments (PLAC; 377 ± 117 s vs. PA; 364 ± 128 s, p = 0.61). Cardiovascular and thermoregulatory responses to exercise were not different between treatments on either day of exercise testing. Polyphenol antioxidant supplementation had no impact on exercise performance and did not alter the cardiovascular or thermoregulatory responses to exercise in the heat.

Trinity, Joel D.; Pahnke, Matthew D.; Trombold, Justin R.; Coyle, Edward F.

2014-01-01

85

Function of cyclins in regulating the mitotic and meiotic cell cycles in male germ cells  

PubMed Central

The specialized cell cycles that characterize various aspects of the differentiation of germ cells provide a unique opportunity to understand heretofore elusive aspects of the in vivo function of cell cycle regulators. Key components of the cell cycle machinery are the regulatory sub-units, the cyclins, and their catalytic partners, the cyclin-dependent kinases. Some of the cyclins exhibit unique patterns of expression in germ cells that suggest possible concomitant distinct functions, predictions that are being explored by targeted mutagenesis in mouse models. A novel, meiosis-specific function has been shown for one of the A-type cyclins, cyclin A1. Embryonic lethality has obviated understanding of the germline functions of cyclin A2 and cyclin B1, while yet other cyclins, although expressed at specific stages of germ cell development, may have less essential function in the male germline.

Wolgemuth, Debra J.

2014-01-01

86

Dwell Time and Surface Parameter Effects on Removal of Silicone Oil From D6ac Steel Using TCA  

NASA Technical Reports Server (NTRS)

This study was conducted to evaluate the impact of dwell time, surface roughness, and the surface activation state on 1,1,1-trichloroethane's (TCA's) effectiveness for removing silicone oil from D6ac steel. Silicone-contaminated test articles were washed with TCA solvent, and then the surfaces were analyzed for residue, using Fourier transform infrared spectroscopy. The predominant factor affecting the ability to remove the silicone oil was surface roughness.

Boothe, R. E.

2003-01-01

87

MicroRNA-145 inhibits the proliferation, migration and invasion of the human TCA8113 oral cancer line  

PubMed Central

The aim of this study was to investigate the effect of microRNA (miR)-145 on the proliferation, migration and invasion of the human oral cancer line, TCA8113. Expression levels of miR-145 in TCA8113 cells were detected by quantitative PCR. miR-145 was transfected into human TCA8113 oral cancer cells and the proliferation, migration and invasion abilities of treated TCA8113 cells were detected by proliferation, migration and invasion assays, respectively. The expression levels of miR-145 in TCA8113 cells were significantly lower than those in human normal oral keratinocytes (P<0.05). Cellular proliferation, migration and invasion abilities in the miR-145 transfection group were significantly lower than those in the control group (all P<0.05). High miR-145 expression was found to negatively regulate the proliferation, migration and invasion of TCA8113 cells. Results of the present study indicate that the expression of miR-145 may be associated with the genesis and development of human oral cancer.

SHAO, YUAN; ZHANG, SHAO-QIANG; QUAN, FANG; ZHANG, PENG-FEI; WU, SHENG-LI

2013-01-01

88

Menstrual Cycle-Related Changes of Functional Cerebral Asymmetries in Fine Motor Coordination  

ERIC Educational Resources Information Center

Fluctuating sex hormone levels during the menstrual cycle have been shown to affect functional cerebral asymmetries in cognitive domains. These effects seem to result from the neuromodulatory properties of sex hormones and their metabolites on interhemispheric processing. The present study was carried out to investigate whether functional cerebral…

Bayer, Ulrike; Hausmann, Markus

2012-01-01

89

Functional product life-cycle simulation model for cost estimation in conceptual design of jet engine components  

Microsoft Academic Search

As functional (total care) products emerge in the jet engine industry, the need for product life-cycle models capable of definition and evaluation of life cycle properties increases, since functional products (FP) includes both hardware and service. Recent life-cycle models are intended for hardware products and mostly handle design and manufacturing knowledge. The aim of this article is to present a

Marcus Sandberg; Patrik Boart; Tobias Larsson

2005-01-01

90

Using Mutant Cycle Analysis to Elucidate Long-Range Functional Coupling in Allosteric Receptors  

PubMed Central

The functional coupling of residues that are far apart in space is the quintessential property of allosteric receptors. Data from functional studies of allosteric receptors, such as whole-cell dose-response relations, can be used to determine if mutation to a receptor significantly impacts agonist potency. However, the classification of perturbations as primarily impacting binding or allosteric function is more challenging, often requiring detailed kinetic studies. This protocol describes a simple strategy, derived from mutant cycle analysis, for elucidating long-range functional coupling in allosteric receptors (ELFCAR). Introduction of a gain-of-function reporter mutation, followed by a mutant cycle analysis of the readily-measured macroscopic EC50 values can provide insight into the role of many physically distant targets. This new method should find broad application in determining the functional roles of residues in allosteric receptors.

Shanata, Jai A. P.; Frazier, Shawnalea J.; Lester, Henry A.; Dougherty, Dennis A.

2014-01-01

91

Knockdown of FAK inhibits the invasion and metastasis of Tca?8113 cells in vitro.  

PubMed

Tongue cancer originating on the surface of the tongue is most commonly squamous cell carcinoma, which has a higher invasive ability and a lower survival rate compared with other forms of tongue cancer. Notably, tongue squamous cell carcinomas metastasize into lymph nodes at early stages. Focal adhesion kinase (FAK) is an important protein tyrosine kinase involved in invasion and metastasis of cancer cells. In the present study, the role of FAK in the invasion and metastasis of tongue cancer was evaluated and the underlying mechanisms involved in this process were explored. FAK knockdown was performed using shRNA in the tongue cancer cell line, Tca?8113, and the invasion and metastasis potentials were analyzed using wound healing and transwell assays, respectively. Cytoskeletal arrangement was detected by fluorescence using TRITC?conjugated phalloidin staining. The activity of matrix metalloproteinase (MMP)?2 and ?9 was examined by gelatin zymography. Paxillin distribution was observed by immunofluorescence. The levels of E?cadherin, N?cadherin, MMP?2 and ?9, and c?Jun N?terminal kinase (JNK) was detected by western blot analysis. Wound healing and transwell assays demonstrated that FAK knockdown inhibited the invasion and metastasis of Tca?8113 cells. Further analysis revealed that FAK knockdown caused the rearrangement of the cytoskeleton and decreased the activity of MMP?2 and ?9. Immunofluorescence analysis revealed that downregulation of FAK induced the relocalization of paxillin. Paxillin accumulated as dots and patches at the cell membrane in control cells. By contrast, in FAK knockdown cells, paxillin was distributed homogeneously in the cytoplasm. Western blot analysis revealed that FAK knockdown inhibited epithelial-mesenchymal transition (EMT) and decreased levels of MMP?2 and ?9, and p?JNK. Knockdown of FAK inhibits the invasion and metastasis of Tca?8113 by decreasing MMP?2 and ?9 activities and led to the rearrangement of the cytoskeleton and inhibited the EMT. PMID:23807215

Xiao, Wenbo; Jiang, Mingxin; Li, Hongdan; Li, Chunshan; Su, Rongjian; Huang, Keqiang

2013-08-01

92

CYCLE INTEGRALS OF THE J-FUNCTION AND MOCK MODULAR FORMS  

Microsoft Academic Search

In this paper we construct certain mock modular forms of weight 1\\/2 whose Fourier coe!cients are cycle integrals of the modular j-function and whose shadows are weakly holo- morphic forms of weight 3\\/2. As an application we construct through a Shimura-type lift a holomorphic function that transforms with a rational period function having poles at certain real quadratic integers. This

W. DUKE; O. IMAMO

93

The multiple hats of Vasa function and its regulation of cell cycle progression  

PubMed Central

Summary Vasa, an ATP-dependent RNA helicase, is broadly conserved among various organisms from cnidarians to mammals. It has a rich history of utility as a germline marker, and is believed to function as a positive translational regulator in the determination and maintenance of germline cells. Studies in non-model organisms, however, revealed that Vasa is also present in somatic cells of many tissues. In many cases these cells are multipotent, are non-germline associated, and give rise to a variety of different tissue types. Recent work now also demonstrates that Vasa functions in the regulation of the cell cycle. Here we discuss this newly described function of Vasa in mitotic and meiotic cell cycles, and we address the conundrum created within these observations, that is, that most cells are mitotically independent of Vasa, yet when Vasa is present in a cell, it appears to be essential for cell cycle progression.

Yajima, Mamiko; Wessel, Gary M.

2011-01-01

94

Enhanced cycle performance of Li-S battery with a polypyrrole functional interlayer  

NASA Astrophysics Data System (ADS)

Polypyrrole functional interlayer is in-situ fabricated uniformly onto the surface of sulfur cathode to inhibit the dissolution of lithium polysulfides and protect sulfur cathode. Li-S battery with the functional inlayer shows an encouraging electrochemical performance. The initial discharge capacity is 719 mAh g-1 and the capacity retains at 846 mAh g-1 even after 200 cycles at 0.2C with an average coulombic efficiency of 94.2%. Moreover, the discharge capacities are 703 mAh g-1 and 533 mAh g-1 at 1C and 2C respectively even after 300 cycles.

Ma, Guoqiang; Wen, Zhaoyin; Jin, Jun; Wu, Meifen; Wu, Xiangwei; Zhang, Jingchao

2014-12-01

95

Metabolic futile cycles and their functions: a systems analysis of energy and control.  

PubMed

It has long been hypothesised that futile cycles in cellular metabolism are involved in the regulation of biochemical pathways. Following the work of Newsholme and Crabtree, a quantitative theory was developed for this idea based on open-system thermodynamics and metabolic control analysis. It is shown that the stoichiometric sensitivity of an intermediary metabolite concentration with respect to changes in steady-state flux is governed by the effective equilibrium constant of the intermediate formation, and the equilibrium can be regulated by a futile cycle. The direction of the shift in the effective equilibrium constant depends on the direction of operation of the futile cycle. High stoichiometric sensitivity corresponds to ultrasensitivity of an intermediate concentration to net flow through a pathway; low stoichiometric sensitivity corresponds to super-robustness of concentration with respect to changes in flux. Both cases potentially play important roles in metabolic regulation. Futile cycles actively shift the effective equilibrium by expending energy; the magnitude of changes in effective equilibria and sensitivities is a function of the amount of energy used by a futile cycle. This proposed mechanism for control by futile cycles works remarkably similar to kinetic proofreading in biosynthesis. The sensitivity of the system is also intimately related to the rate of concentration fluctuations of intermediate metabolites. The possibility of different roles for the two major mechanisms within cellular biochemical regulation, namely reversible chemical modifications via futile cycles and shifting equilibrium by macromolecular binding, are discussed. PMID:16986621

Qian, H; Beard, D A

2006-07-01

96

A generalized frequency modified damage function model for high temperature low cycle fatigue life prediction  

Microsoft Academic Search

The models for predicting high temperature low cycle fatigue (HTLCF) life are significant in the design of engineering components and structures working under high temperature and cyclic loading. In this paper, a review of the earlier models is given first, and then a new model for the HTLCF life prediction, a generalized frequency modified damage function (GFMDF) model, is set

Wang Yonglian

1997-01-01

97

Elimination of limit cycles in HVAC systems using the describing function method  

Microsoft Academic Search

In heating, ventilating and air conditioning systems, the presence of undesirable limit cycles is a common problem. This paper outlines the application of the well known describing function method to the analysis and synthesis of a temperature control system used for air-conditioning an office room. PI-controllers are most commonly used in this field of application. In the present case, an

Jakob Rehrl; Martin Horn; Markus Reichhartinger

2009-01-01

98

CHLORINATION BY-PRODUCTS IN DRINKING WATER AND MENSTRUAL CYCLE FUNCTION  

EPA Science Inventory

Chlorination by-Products in Drinking Water and Menstrual Cycle Function Gayle C. Windham1, Kirsten Waller2, Meredith Anderson2, Laura Fenster1, Pauline Mendola3, Shanna Swan4 1California Department of Health Services, Division of Environmental and Occupational Disea...

99

The Dual-Functioning Fumarate Reductase Is the Sole Succinate:Quinone Reductase in Campylobacter jejuni and Is Required for Full Host Colonization  

Microsoft Academic Search

Campylobacter jejuni encodes all the enzymes necessary for a complete oxidative tricarboxylic acid (TCA) cycle. Because of its inability to utilize glucose, C. jejuni relies exclusively on amino acids as the source of reduced carbon, and they are incorporated into central carbon metabolism. The oxidation of succinate to fumarate is a key step in the oxidative TCA cycle. C. jejuni

Rebecca A. Weingarten; Michael E. Taveirne; Jonathan W. Olson

2009-01-01

100

Structural rearrangement of ebola virus VP40 begets multiple functions in the virus life cycle.  

PubMed

Proteins, particularly viral proteins, can be multifunctional, but the mechanisms behind multifunctionality are not fully understood. Here, we illustrate through multiple crystal structures, biochemistry, and cellular microscopy that VP40 rearranges into different structures, each with a distinct function required for the ebolavirus life cycle. A butterfly-shaped VP40 dimer traffics to the cellular membrane. Once there, electrostatic interactions trigger rearrangement of the polypeptide into a linear hexamer. These hexamers construct a multilayered, filamentous matrix structure that is critical for budding and resembles tomograms of authentic virions. A third structure of VP40, formed by a different rearrangement, is not involved in virus assembly but instead uniquely binds RNA to regulate viral transcription inside infected cells. These results provide a functional model for ebolavirus matrix assembly and the other roles of VP40 in the virus life cycle and demonstrate how a single wild-type, unmodified polypeptide can assemble into different structures for different functions. PMID:23953110

Bornholdt, Zachary A; Noda, Takeshi; Abelson, Dafna M; Halfmann, Peter; Wood, Malcolm R; Kawaoka, Yoshihiro; Saphire, Erica Ollmann

2013-08-15

101

Power output during functional electrically stimulated cycling in trained spinal cord injured people.  

PubMed

Objectives.?This study is to compare relationships between muscle size, strength, and power output (PO) in trained spinal cord injured (SCI) people and able-bodied (AB) people; and to compare methodologies for measuring PO during functional electrically stimulated (FES) cycling. Subjects.?Trained SCI people (N= 5) and five AB subjects of similar physical characteristics. Materials and Methods.?Thickness and strength of the quadriceps muscles and PO during 1) incremental exercise test (IET); 2) maximal stimulation test (MST) in SCI people and during an explosive exercise test in AB subjects. Results.?In SCI people, muscle thickness, strength, and peak PO reached 88, 34, and 13% of AB, respectively. Steady state PO (MST) was similar to maximal PO (IET). Conclusions.?Peak PO was lower than expected in trained SCI people. Muscle recruitment and efficiency during FES cycling require optimization to improve PO. An MST is a more convenient and informative measure of PO during FES cycling. PMID:21992765

Duffell, Lynsey Diane; Donaldson, Nick de Neufville; Newham, Di Jane

2010-01-01

102

Functional roles of PC-PLC and Cdc20 in the cell cycle, proliferation, and apoptosis.  

PubMed

Phosphatidylcholine-specific phospholipase C (PC-PLC) is the major enzyme in the Phosphatidylcholine (PC) cycle and is involved in many long-term cellular responses such as activation, proliferation, and differentiation events. Cell division cycle 20 homolog (Cdc20) is an essential cell-cycle regulator required for the completion of mitosis. Our previous studies identified the interaction between PC-PLC and Cdc20. Through the interaction, Cdc20 could mediate the degradation of PC-PLC by Cdc20-mediated ubiquitin proteasome pathway (UPP). In this study, we found that PC-PLC might not be involved in cancer metastasis. Inhibition of PC-PLC by D609 could cause cell proliferation inhibition and apoptosis inhibition in CBRH-7919 cells. Inhibition of PC-PLC could also influence the cell cycle by arresting the cells in G1 phase, and Cdc20 might be involved in these processes. Taken together, in this report, we provided new evidence for the functional roles of PC-PLC and Cdc20 in the cell cycle, proliferation, and apoptosis in CBRH-7919 cells. PMID:20517887

Chen, Zhiwei; Yu, Yongfeng; Fu, Da; Li, Ziming; Niu, Xiaoming; Liao, Meilin; Lu, Shun

2010-06-01

103

Effect of fluid ingestion on neuromuscular function during prolonged cycling exercise  

PubMed Central

Objectives: To investigate the effects of fluid ingestion on neuromuscular function during prolonged cycling exercise. Methods: Eight well trained subjects exercised for 180 minutes in a moderate environment at a workload requiring ?60% maximal oxygen uptake. Two conditions, fluid (F) and no fluid (NF) ingestion, were investigated. Results: During maximal voluntary isometric contraction (MVC), prolonged cycling exercise reduced (p<0.05) the maximal force generating capacity of quadriceps muscles (after three hours of cycling) and root mean square (RMS) values (after two hours of cycling) with no difference between the two conditions despite greater body weight loss (p<0.05) in NF. The mean power frequency (MPF) for vastus lateralis muscle was reduced (p<0.05) and the rate of force development (RFD) was increased (p<0.05) only during NF. During cycling exercise, integrated electromyographic activity and perceived exertion were increased in both conditions (p<0.05) with no significant effect of fluid ingestion. Conclusions: The results suggest that fluid ingestion did not prevent the previously reported decrease in maximal force with exercise duration, but seems to have a positive effect on some indicators of neuromuscular fatigue such as mean power frequency and rate of force development during maximal voluntary contraction. Further investigations are needed to assess the effect of change in hydration on neural mechanisms linked to the development of muscular fatigue during prolonged exercise.

Vallier, J; Grego, F; Basset, F; Lepers, R; Bernard, T; Brisswalter, J

2005-01-01

104

Cell cycle progression is required for zebrafish somite morphogenesis but not segmentation clock function  

PubMed Central

Summary Cell division, differentiation and morphogenesis are coordinated during embryonic development and frequently in disarray in pathologies such as cancer. Here, we present a zebrafish mutant that ceases mitosis at the beginning of gastrulation, but undergoes axis elongation and develops blood, muscle and a beating heart. We identify the mutation as being in early mitotic inhibitor 1 (emi1), a negative regulator of the Anaphase Promoting Complex, and utilize the mutant to examine the role of the cell cycle in somitogenesis. The mutant phenotype indicates that axis elongation during the segmentation period is substantially driven by cell migration. We find that the segmentation clock, which regulates somitogenesis, functions normally in the absence of cell cycle progression and observe that mitosis is a modest source of noise for the clock. Somite morphogenesis involves the epithelialization of the somite border cells around a core of mesenchyme. As in wild-type embryos, somite boundary cells are polarized along a Fibronectin matrix in emi1?/?. The mutants also display evidence of segment polarity. However, in the absence of a normal cell cycle, somites appear to hyper-epithelialize as the internal mesenchymal cells exit the core of the somite after initial boundary formation. Thus, cell cycle progression is not required during the segmentation period for segmentation clock function but is necessary for normal segmental arrangement of epithelial borders and internal mesenchymal cells.

Zhang, Lixia; Kendrick, Christina; Julich, Dorthe; Holley, Scott A.

2010-01-01

105

A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis.  

PubMed

In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a. PMID:23948297

Kollmann, Karoline; Heller, Gerwin; Schneckenleithner, Christine; Warsch, Wolfgang; Scheicher, Ruth; Ott, Rene G; Schäfer, Markus; Fajmann, Sabine; Schlederer, Michaela; Schiefer, Ana-Iris; Reichart, Ursula; Mayerhofer, Matthias; Hoeller, Christoph; Zöchbauer-Müller, Sabine; Kerjaschki, Dontscho; Bock, Christoph; Kenner, Lukas; Hoefler, Gerald; Freissmuth, Michael; Green, Anthony R; Moriggl, Richard; Busslinger, Meinrad; Malumbres, Marcos; Sexl, Veronika

2013-08-12

106

A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis  

PubMed Central

Summary In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6’s kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6’s central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a.

Kollmann, Karoline; Heller, Gerwin; Schneckenleithner, Christine; Warsch, Wolfgang; Scheicher, Ruth; Ott, Rene G.; Schafer, Markus; Fajmann, Sabine; Schlederer, Michaela; Schiefer, Ana-Iris; Reichart, Ursula; Mayerhofer, Matthias; Hoeller, Christoph; Zochbauer-Muller, Sabine; Kerjaschki, Dontscho; Bock, Christoph; Kenner, Lukas; Hoefler, Gerald; Freissmuth, Michael; Green, Anthony R.; Moriggl, Richard; Busslinger, Meinrad; Malumbres, Marcos; Sexl, Veronika

2013-01-01

107

Controllable spin-dynamics cycles and ERASE functionality on quasilinear molecular ions  

NASA Astrophysics Data System (ADS)

We present an ab initio investigation of the ?-process-based ultrafast spin manipulation on positively charged two-magnetic-center molecular ions with a nonmagnetic bridging atom O in-between. Multiple spin-switching and spin-transfer scenarios are derived on the quasilinear structure [Fe-O-Co]+, which are used to build two closed, irreversible spin-dynamics cycles with respect to the spin localization and orientation. A mechanism addressing the "ERASE" functionality is proposed by properly exploiting the irreversibility of some laser-induced spin-manipulation scenarios, and the resulting Shannon entropy change is analyzed. Such controllable spin-dynamics cycles and logic functionality demonstrate promising applications in the design of spintronic devices.

Li, Chun; Zhang, Shaobin; Jin, Wei; Lefkidis, Georgios; Hübner, Wolfgang

2014-05-01

108

Integrative Functional Genomics of Hepatitis C Virus Infection Identifies Host Dependencies in Complete Viral Replication Cycle  

PubMed Central

Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase ?, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host dependencies yields novel insights into viral infection, pathogenesis and potential therapeutic targets.

Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T. Jake

2014-01-01

109

Screening life cycle impact assessment with weighting methodology based on simplified damage functions  

Microsoft Academic Search

The procedure of screening LCIA with weighting methodology and the result of a case study have been described. The weighting\\u000a methodology incorporates the impacts related with input and output by the simplified damage functions. Through the dominant\\u000a analysis by this methodology, we can detect the significant substances and environmental problems in life cycle of the product.\\u000a With this result, LCA

Norihiro Itsubo

2000-01-01

110

Alterations in neuromuscular function and perceptual responses following acute eccentric cycling exercise  

Microsoft Academic Search

Previous investigators have reported velocity-dependent strength loss for single-joint actions following acute eccentric exercise.\\u000a The extent to which velocity influences recovery of multi-joint function is not well documented. Our main purpose was to compare\\u000a alterations in maximal cycling power produced across a range of pedaling rates following eccentric exercise. An additional\\u000a purpose was to determine the extent to which changes

Steven J. Elmer; John McDaniel; James C. Martin

2010-01-01

111

Integrative functional genomics of hepatitis C virus infection identifies host dependencies in complete viral replication cycle.  

PubMed

Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase ?, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host dependencies yields novel insights into viral infection, pathogenesis and potential therapeutic targets. PMID:24852294

Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T Jake

2014-05-01

112

Functional unit, technological dynamics, and scaling properties for the life cycle energy of residences.  

PubMed

Prior LCA studies take the operational phase to include all energy use within a residence, implying a functional unit of all household activities, but then exclude related supply chains such as production of food, appliances, and household chemicals. We argue that bounding the functional unit to provision of a climate controlled space better focuses the LCA on the building, rather than activities that occur within a building. The second issue explored in this article is how technological change in the operational phase affects life cycle energy. Heating and cooling equipment is replaced at least several times over the lifetime of a residence; improved efficiency of newer equipment affects life cycle energy use. The third objective is to construct parametric models to describe LCA results for a family of related products. We explore these three issues through a case study of energy use of residences: one-story and two-story detached homes, 1,500-3,500 square feet in area, located in Phoenix, Arizona, built in 2002 and retired in 2051. With a restricted functional unit and accounting for technological progress, approximately 30% of a building's life cycle energy can be attributed to materials and construction, compared to 0.4-11% in previous studies. PMID:22192002

Frijia, Stephane; Guhathakurta, Subhrajit; Williams, Eric

2012-02-01

113

Dwell Time and Surface Parameter Effects on Removal of Silicone Oil From D6ac Steel Using TCA.  

National Technical Information Service (NTIS)

This study was conducted to evaluate the impact of dwell time, surface roughness, and the surface activation state on 1,1,1-trichloroethane's (TCA's) effectiveness for removing silicone oil from D6ac steel. Silicone-contaminated test articles were washed ...

R. E. Boothe

2003-01-01

114

Extraction-less, rapid assay for the direct detection of 2,4,6-trichloroanisole (TCA) in cork samples.  

PubMed

2,4,6-trichloroanisole (TCA), the cork taint molecule, has been the target of several analytical approaches over the few past years. In spite of the development of highly efficient and sensitive tools for its detection, ranging from advanced chromatography to biosensor-based techniques, a practical breakthrough for routine cork screening purposes has not yet been realized, in part due to the requirement of a lengthy extraction of TCA in organic solvents, mostly 12% ethanol and the high detectability required. In the present report, we present a modification of a previously reported biosensor system based on the measurement of the electric response of cultured fibroblast cells membrane-engineered with the pAb78 TCA-specific antibody. Samples were prepared by macerating cork tissue and mixing it directly with the cellular biorecognition elements, without any intervening extraction process. By using this novel approach, we were able to detect TCA in just five minutes at extremely low concentrations (down to 0.2ppt). The novel biosensor offers a number of practical benefits, including a very considerable reduction in the total assay time by one day, and a full portability, enabling its direct employment for on-site, high throughput screening of cork in the field and production facilities, without requiring any type of supporting infrastructure. PMID:24840453

Apostolou, Theofylaktos; Pascual, Nuria; Marco, M-Pilar; Moschos, Anastassios; Petropoulos, Anastassios; Kaltsas, Grigoris; Kintzios, Spyridon

2014-07-01

115

National exposure registry volatile organic compounds registry 1,1,1-trichloroethane (TCA) subregistry baseline and followup 1 technical report. Final report  

SciTech Connect

This report describes the baseline activities and results of the statistical analyses of the baseline and first follow-up data for the TCA Subregistry of the Volatile Organic Compounds Registry of the National Exposure Registry. The TCA Subregistry baseline data contains information on 3,665 persons who had documented exposure to TCA in their drinking water and were exposed for at least 30 days; the follow-up files contain information on 3,469 persons. The individuals included in the TCA Subregistry resided at a site in Vestal, New York. The findings in this report cannot be used to identify a causal relationship between the health outcomes and TCA exposure. In addition, there are some methodological differences in data collection that might have biased the reporting rates, resulting in false positive findings. The findings of this report do, however, reinforce the need to continue regular followup of this population.

Burg, J.R.; Gist, G.L.

1996-05-01

116

Fabrication of functionally gradient nanocomposite coatings by plasma electrolytic oxidation based on variable duty cycle  

NASA Astrophysics Data System (ADS)

Plasma electrolytic oxidation (PEO) was applied on the surface of commercially pure titanium substrates in a mixed aluminate-phosphate electrolyte in the presence of silicon nitride nanoparticles as suspension in the electrolyte in order to fabricate nanocomposite coatings. Pulsed current was applied based on variable duty cycle in order to synthesize functionally gradient coatings (FGC). Different rates of variable duty cycle (3, 1.5 and 1%/min), applied current densities (0.06-0.14 A/cm 2) and concentrations of nanoparticles in the electrolyte (2, 4, 6, 8 and 10 g l -1) were investigated. The nanopowder and coated samples were analyzed by atomic force microscope, scanning electron microscope and transmission electron microscope. The influence of different rates of variable duty cycle (or treatment times) on the growth rate of nanocomposite coatings and their microhardness values was investigated. The experimental results revealed that the content of Si 3N 4 nanoparticulates in the layer increases with the increase of its concentration in the plasma electrolysis bath. Nanocomposite coatings fabricated with lower rate of variable duty cycle have higher microhardness with smoother microhardness profile.

Aliofkhazraei, M.; Rouhaghdam, A. Sabour

2012-01-01

117

HESS Opinions "Biological catalysis of the hydrological cycle: life's thermodynamic function"  

NASA Astrophysics Data System (ADS)

Darwinian theory depicts life as being overwhelmingly consumed by a fight for survival in a hostile environment. However, from a thermodynamic perspective, life is a dynamic, out of equilibrium process, stabilizing and coevolving in concert with its abiotic environment. The living components of the biosphere on the Earth's surface of greatest biomass, the plants and cyanobacteria, are involved in the transpiration of a vast amount of water. Transpiration is part of the global water cycle, and it is this cycle that distinguishes Earth from its apparently life-barren neighboring planets, Venus and Mars. The dissipation of sunlight into heat by organic molecules in the biosphere, and its coupling to the water cycle (as well as other abiotic processes), is by far the greatest entropy-producing process occurring on Earth. Life, from this perspective, can be viewed as performing an important thermodynamic function, acting as a dynamic catalyst by aiding irreversible abiotic processes such as the water cycle, hurricanes, and ocean and wind currents to produce entropy. The role of animals in this view is that of unwitting but dedicated servants of the plants and cyanobacteria, helping them to grow, and to spread into initially inhospitable areas.

Michaelian, K.

2012-08-01

118

The tricarboxylic acid cycle in Shewanella oneidensis is independent of Fur and RyhB control  

Microsoft Academic Search

BACKGROUND: It is well established in E. coli and Vibrio cholerae that strains harboring mutations in the ferric uptake regulator gene (fur) are unable to utilize tricarboxylic acid (TCA) compounds, due to the down-regulation of key TCA cycle enzymes, such as AcnA and SdhABCD. This down-regulation is mediated by a Fur-regulated small regulatory RNA named RyhB. It is unclear in

Yunfeng Yang; Lee Ann McCue; Andrea B Parsons; Sheng Feng; Jizhong Zhou

2010-01-01

119

Lung function changes in relation to menstrual cycle in females with cystic fibrosis.  

PubMed

Oestrogen and progesterone have been shown to have impact on cystic fibrosis transmembrane conductance regulator (CFTR) gene expression, tone of smooth muscle in the airways, immune response, exhaled nitric oxide and cytology in the tracheobronchial epithelium. The aim of this investigation was to study the influence of menstrual cyclicity on airway symptoms among cystic fibrosis (CF) females. Twelve CF women (mean age 30 years, mean Shwachman score 85) kept daily records during three menstrual cycles of lung function, sputum quality and need for intravenous antibiotics. Paired t-test was used as a statistical method to compare the airway symptoms between the time of ovulation (high levels of oestrogen and low levels of progesterone), the luteal phase (high levels of oestrogen and progesterone) and menstruation (low levels of oestrogens and progesterone). Forced expiratory volume in 1 sec (FEV1) was significantly higher during the luteal phase (66% of predicted) compared to during ovulation (63%) and menstruation (61%) (P<0.01). Forced vital capacity (FVC) showed the same pattern, being significantly higher during the luteal phase compared with during menstruation (mean 75% vs. 70%, P<0.01). In conclusion, lung function changes were found during menstrual cycles in women with cystic fibrosis. These changes are probably related to changes in progesterone levels during the menstrual cycles. This result warrants further studies to understand the complexity of CF lung disease in women. PMID:11127489

Johannesson, M; Lúdvíksdóttir, D; Janson, C

2000-11-01

120

Modeling the High Speed Research Cycle 2B Longitudinal Aerodynamic Database Using Multivariate Orthogonal Functions  

NASA Technical Reports Server (NTRS)

The data for longitudinal non-dimensional, aerodynamic coefficients in the High Speed Research Cycle 2B aerodynamic database were modeled using polynomial expressions identified with an orthogonal function modeling technique. The discrepancy between the tabular aerodynamic data and the polynomial models was tested and shown to be less than 15 percent for drag, lift, and pitching moment coefficients over the entire flight envelope. Most of this discrepancy was traced to smoothing local measurement noise and to the omission of mass case 5 data in the modeling process. A simulation check case showed that the polynomial models provided a compact and accurate representation of the nonlinear aerodynamic dependencies contained in the HSR Cycle 2B tabular aerodynamic database.

Morelli, E. A.; Proffitt, M. S.

1999-01-01

121

Functional near infrared spectroscopy study of age-related difference in cortical activation patterns during cycling with speed feedback.  

PubMed

Functional decline of lower-limb affects the ability of locomotion and the age-related brain differences have been elucidated among the elderly. Cycling exercise is a common training program for restoring motor function in the deconditioned elderly or stroke patients. The provision of speed feedback has been commonly suggested to clinical therapists for facilitating learning of controlled cycling performance and maintaining motivation in training programs with elderly participants. However, the cortical control of pedaling movements and the effect of external feedback remain poorly understanding. This study investigated the regional cortical activities detected by functional near infrared spectroscopy (fNIRS) in 12 healthy young and 13 healthy elderly subjects under conditions of cycling without-(free cycling) and with feedback (target cycling). The elderly exhibited predominant activation of the sensorimotor cortex during free cycling similar to young subjects but with poorer cycling performance. The cycling performance improved in both groups, and the elderly showed increased brain activities of the supplementary motor area and premotor cortex under target cycling condition. These findings demonstrated age-related changes in the cortical control in processing external feedback and pedaling movements. Use of fNIRS to evaluate brain activation patterns after training may facilitate brain-based design of tailored therapeutic rehabilitation strategies. PMID:21984524

Lin, Pei-Yi; Lin, Sang-I; Chen, Jia-Jin J

2012-01-01

122

Biostimulation induces syntrophic interactions that impact C, S and N cycling in a sediment microbial community.  

PubMed

Stimulation of subsurface microorganisms to induce reductive immobilization of metals is a promising approach for bioremediation, yet the overall microbial community response is typically poorly understood. Here we used proteogenomics to test the hypothesis that excess input of acetate activates complex community functioning and syntrophic interactions among autotrophs and heterotrophs. A flow-through sediment column was incubated in a groundwater well of an acetate-amended aquifer and recovered during microbial sulfate reduction. De novo reconstruction of community sequences yielded near-complete genomes of Desulfobacter (Deltaproteobacteria), Sulfurovum- and Sulfurimonas-like Epsilonproteobacteria and Bacteroidetes. Partial genomes were obtained for Clostridiales (Firmicutes) and Desulfuromonadales-like Deltaproteobacteria. The majority of proteins identified by mass spectrometry corresponded to Desulfobacter-like species, and demonstrate the role of this organism in sulfate reduction (Dsr and APS), nitrogen fixation and acetate oxidation to CO2 during amendment. Results indicate less abundant Desulfuromonadales, and possibly Bacteroidetes, also actively contributed to CO2 production via the tricarboxylic acid (TCA) cycle. Proteomic data indicate that sulfide was partially re-oxidized by Epsilonproteobacteria through nitrate-dependent sulfide oxidation (using Nap, Nir, Nos, SQR and Sox), with CO2 fixed using the reverse TCA cycle. We infer that high acetate concentrations, aimed at stimulating anaerobic heterotrophy, led to the co-enrichment of, and carbon fixation in Epsilonproteobacteria. Results give an insight into ecosystem behavior following addition of simple organic carbon to the subsurface, and demonstrate a range of biological processes and community interactions were stimulated. PMID:23190730

Handley, Kim M; VerBerkmoes, Nathan C; Steefel, Carl I; Williams, Kenneth H; Sharon, Itai; Miller, Christopher S; Frischkorn, Kyle R; Chourey, Karuna; Thomas, Brian C; Shah, Manesh B; Long, Philip E; Hettich, Robert L; Banfield, Jillian F

2013-04-01

123

Biostimulation induces syntrophic interactions that impact C, S and N cycling in a sediment microbial community  

PubMed Central

Stimulation of subsurface microorganisms to induce reductive immobilization of metals is a promising approach for bioremediation, yet the overall microbial community response is typically poorly understood. Here we used proteogenomics to test the hypothesis that excess input of acetate activates complex community functioning and syntrophic interactions among autotrophs and heterotrophs. A flow-through sediment column was incubated in a groundwater well of an acetate-amended aquifer and recovered during microbial sulfate reduction. De novo reconstruction of community sequences yielded near-complete genomes of Desulfobacter (Deltaproteobacteria), Sulfurovum- and Sulfurimonas-like Epsilonproteobacteria and Bacteroidetes. Partial genomes were obtained for Clostridiales (Firmicutes) and Desulfuromonadales-like Deltaproteobacteria. The majority of proteins identified by mass spectrometry corresponded to Desulfobacter-like species, and demonstrate the role of this organism in sulfate reduction (Dsr and APS), nitrogen fixation and acetate oxidation to CO2 during amendment. Results indicate less abundant Desulfuromonadales, and possibly Bacteroidetes, also actively contributed to CO2 production via the tricarboxylic acid (TCA) cycle. Proteomic data indicate that sulfide was partially re-oxidized by Epsilonproteobacteria through nitrate-dependent sulfide oxidation (using Nap, Nir, Nos, SQR and Sox), with CO2 fixed using the reverse TCA cycle. We infer that high acetate concentrations, aimed at stimulating anaerobic heterotrophy, led to the co-enrichment of, and carbon fixation in Epsilonproteobacteria. Results give an insight into ecosystem behavior following addition of simple organic carbon to the subsurface, and demonstrate a range of biological processes and community interactions were stimulated.

Handley, Kim M; VerBerkmoes, Nathan C; Steefel, Carl I; Williams, Kenneth H; Sharon, Itai; Miller, Christopher S; Frischkorn, Kyle R; Chourey, Karuna; Thomas, Brian C; Shah, Manesh B; Long, Philip E; Hettich, Robert L; Banfield, Jillian F

2013-01-01

124

Acute Bouts of Assisted Cycling Improves Cognitive and Upper Extremity Movement Functions in Adolescents with Down Syndrome  

ERIC Educational Resources Information Center

The aim of this study was to examine the effectiveness of 2 modes of exercise on cognitive and upper extremity movement functioning in adolescents with Down syndrome (DS). Nine participants randomly completed 3 interventions over 3 consecutive weeks. The interventions were: (a) voluntary cycling (VC), in which participants cycled at their…

Ringenbach, Shannon D. R; Albert, Andrew R.; Chen, Chih-Chia; Alberts, Jay L.

2014-01-01

125

Nitrogen cycling in Yellowstone National Park thermal features: using gene expression to reveal ecological function  

NASA Astrophysics Data System (ADS)

Studies of biodiversity, metabolic strategies, and functional ecology in modern hydrothermal systems have the potential to provide insight into the metabolism and evolution of life. The geochemical and microbial diversity present at Yellowstone National Park (YNP), Wyoming, USA, makes it an ideal place for studying the functional ecology and metabolic processes of prokaryotic organisms. While much work in terrestrial hydrothermal features is focused on phylogenetic and geochemical analyses, a few recent investigations in YNP and other hydrothermal areas have focused on “gene hunting”: screening thermal sediment and biofilm samples for the presence of genes utilized in specific metabolic processes [2, 3, 6, 7, 8]. Although research has evaluated and confirmed the presence of many of these genes in various thermophilic microbial communities, the existence of a gene in the DNA of an organism does not verify its use, and few researchers have done work to confirm the utilization (expression) of the genes discovered in thermal samples [1, 6, 7, 8]. Disequilibrium between reduced hydrothermal fluid of YNP thermal features and the atmosphere provides a copious source of potential energy to be harnessed through microbial metabolic processes, with NO3- and NO2- serving as the preferred electron acceptors and top energy sources after O2 [4, 5]. Consequentially, nitrogen cycling likely plays a vital role in microbial metabolic processes, as well as nutrient availability. This study explores the presence and utilization of functional genes that are key in steps of the nitrogen cycle, such as nitrogen fixation (NifH), denitrification (nirKS), and ammonia oxidation (amoA). Both DNA and RNA were extracted from thermal sediment and streamer biofilm communities collected in the chemosynthetic zone of various thermal features of the Sentinel Meadows Group in Lower Geyser Basin, YNP. Extracted DNA and reverse transcribed RNA (cDNA) were amplified using the polymerase chain reaction (PCR), and products were analyzed through gel electrophoresis to identify the presence and expression of the target functional nitrogen cycle genes. Results allow comparison of nitrogen cycling processes between different chemotrophic microbial communities both within and among the thermal features investigated in this study. [1] Botero et al., 2005. AEM 71: 1267-1275. [2] Hall et al., 2008. AEM 74: 4910-4922. [3] Meyer-Dombard et al., 2009. EOS Trans AGU 90. Abstract B23C-0390. [4] Reysenbach & Shock, 2002. Science 296: 1077-1082. [5] Shock et al., 2005. Geochim Cosmochim Acta 74: 4005-4043. [6] Steunou et al., 2006. PNAS 103:2398-2403. [7] Steunou et al., 2008. The ISME Journal 2: 364-378. [8] Zhang et al., 2008. AEM 74: 6417-6426.

Lafree, S. T.; Burton, M. S.; Meyer-Dombard, D. R.

2010-12-01

126

Reproductive functions of kisspeptin and Gpr54 across the life cycle of mice and men  

PubMed Central

The reproductive phenotypes of nearly two dozen patients with mutations in GPR54 have been reported, as have the phenotypes of four mouse lines mutant for Gpr54 and two lines mutant for Kiss1. These phenotypes demonstrate that kisspeptin/Gpr54 function is required at all phases of the life cycle when the secretion of gonadotropin-releasing hormone (GnRH) is robust. Furthermore, there is phenotypic variability ranging from severe hypogonadism to partial sexual development. Collectively, these findings suggest that kisspeptin and Gpr54 serve as an essential conduit for relaying developmental information to the GnRH neuron.

Broder-Fingert, Sarabeth; Seminara, Stephanie B.

2009-01-01

127

Arabidopsis peroxisomal malate dehydrogenase functions in beta-oxidation but not in the glyoxylate cycle.  

PubMed

The aim was to determine the function of peroxisomal NAD(+)-malate dehydrogenase (PMDH) in fatty acid beta-oxidation and the glyoxylate cycle in Arabidopsis. Seeds in which both PMDH genes are disrupted by T-DNA insertions germinate, but seedling establishment is dependent on exogenous sugar. Mutant seedlings mobilize their triacylglycerol very slowly and growth is insensitive to 2,4-dichlorophenoxybutyric acid. Thus mutant seedlings are severely impaired in beta-oxidation, even though microarray analysis shows that beta-oxidation genes are expressed normally. The mutant phenotype was complemented by expression of a cDNA encoding PMDH with either its native peroxisome targeting signal-2 (PTS2) targeting sequence or a heterologous PTS1 sequence. In contrast to the block in beta-oxidation in mutant seedlings, [(14)C]acetate is readily metabolized into sugars and organic acids, thereby demonstrating normal activity of the glyoxylate cycle. We conclude that PMDH serves to reoxidize NADH produced from fatty acid beta-oxidation and does not participate directly in the glyoxylate cycle. PMID:17376163

Pracharoenwattana, Itsara; Cornah, Johanna E; Smith, Steven M

2007-05-01

128

Alterations in dopamine system function across the estrous cycle of the MAM rodent model of schizophrenia.  

PubMed

Clinical studies have reported differences in the incidence and severity of schizophrenia symptoms between male and female schizophrenia patients. Unfortunately, the cause of these differences is not currently known due, in part, to the fact that preclinical studies largely focus on male subjects. Dopamine neuron activity has been previously demonstrated to change across the estrous cycle, and may therefore be of relevance, as aberrant dopamine signaling is thought to underlie the positive symptoms of schizophrenia. Here we examine dopamine neuron activity across the estrous cycle in the MAM rodent model of schizophrenia. We demonstrate that the elevation in dopamine neuron activity, consistently observed in male MAM-treated rats, is most prominent during estrus and attenuated in met-estrus. Furthermore, this appears to be mediated, in part, by progesterone in the ventral hippocampus, as increases in dopamine neuron population activity (observed in estrus) were normalized by the intra-hippocampal administration of the progesterone receptor antagonist, mifepristone (but not the estrogen receptor antagonists, fulvestrant). Taken together, these data suggest that changes in dopamine system function occur across the estrous cycle in MAM-treated rats and may contribute to the differences in symptomatology between male and female schizophrenia patients. PMID:25001958

Perez, Stephanie M; Chen, Li; Lodge, Daniel J

2014-09-01

129

Mechanisms of beat-to-beat regulation of cardiac pacemaker cell function by Ca²? cycling dynamics.  

PubMed

Whether intracellular Ca(2+) cycling dynamics regulate cardiac pacemaker cell function on a beat-to-beat basis remains unknown. Here we show that under physiological conditions, application of low concentrations of caffeine (2-4 mM) to isolated single rabbit sinoatrial node cells acutely reduces their spontaneous action potential cycle length (CL) and increases Ca(2+) transient amplitude for several cycles. Numerical simulations, using a modified Maltsev-Lakatta coupled-clock model, faithfully reproduced these effects, and also the effects of CL prolongation and dysrhythmic spontaneous beating (produced by cytosolic Ca(2+) buffering) and an acute CL reduction (produced by flash-induced Ca(2+) release from a caged Ca(2+) buffer), which we had reported previously. Three contemporary numerical models (including the original Maltsev-Lakatta model) failed to reproduce the experimental results. In our proposed new model, Ca(2+) releases acutely change the CL via activation of the Na(+)/Ca(2+) exchanger current. Time-dependent CL reductions after flash-induced Ca(2+) releases (the memory effect) are linked to changes in Ca(2+) available for pumping into sarcoplasmic reticulum which, in turn, changes the sarcoplasmic reticulum Ca(2+) load, diastolic Ca(2+) releases, and Na(+)/Ca(2+) exchanger current. These results support the idea that Ca(2+) regulates CL in cardiac pacemaker cells on a beat-to-beat basis, and suggest a more realistic numerical mechanism of this regulation. PMID:24094396

Yaniv, Yael; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

2013-10-01

130

Power Effects on High Lift, Stability and Control Characteristics of the TCA Model Tested in the LaRC 14 x 22 Ft Wind Tunnel  

NASA Technical Reports Server (NTRS)

The TCA-2 wind-tunnel test was the second in a series of planned tests utilizing the 5% Technology Concept Airplane (TCA) model. Each of the tests was planned to utilize the unique capabilities of the NASA Langley 14'x22' and the NASA Ames 12' test facilities, in order to assess specific aspects of the high lift and stability and control characteristics of the TCA configuration. However, shortly after the completion of the TCA-1 test, an early projection of the Technology Configuration (TC) identified the need for several significant changes to the baseline TCA configuration. These changes were necessary in order to meet more stringent noise certification levels, as well as, to provide a means to control dynamic structural modes. The projected changes included a change to the outboard wing (increased aspect ratio and lower sweep) and a reconfiguration of the longitudinal control surfaces to include a medium size canard and a reduced horizontal tail. The impact of these proposed changes did not affect the TCA-2 test, because it was specifically planned to address power effects on the empennage and a smaller horizontal tail was in the plan to be tested. However, the focus of future tests was reevaluated and the emphasis was shifted away from assessment of TCA specific configurations to a more general assessment of configurations that encompass the projected design space for the TC.

Glessner, Paul T.

1999-01-01

131

Sparstolonin B inhibits pro-angiogenic functions and blocks cell cycle progression in endothelial cells.  

PubMed

Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 genes, respectively, with fold change ?2, p<0.05, unpaired t-test). Microarray data from both cell types showed significant overlap, including genes associated with cell proliferation and cell cycle. Flow cytometric cell cycle analysis of HUVECs treated with SsnB showed an increase of cells in the G1 phase and a decrease of cells in the S phase. Cyclin E2 (CCNE2) and Cell division cycle 6 (CDC6) are regulatory proteins that control cell cycle progression through the G1/S checkpoint. Both CCNE2 and CDC6 were downregulated in the microarray data. Real Time quantitative PCR confirmed that gene expression of CCNE2 and CDC6 in HUVECs was downregulated after SsnB exposure, to 64% and 35% of controls, respectively. The data suggest that SsnB may exert its anti-angiogenic properties in part by downregulating CCNE2 and CDC6, halting progression through the G1/S checkpoint. In the chick chorioallantoic membrane (CAM) assay, SsnB caused significant reduction in capillary length and branching number relative to the vehicle control group. Overall, SsnB caused a significant reduction in angiogenesis (ANOVA, p<0.05), demonstrating its ex vivo efficacy. PMID:23940584

Bateman, Henry R; Liang, Qiaoli; Fan, Daping; Rodriguez, Vanessa; Lessner, Susan M

2013-01-01

132

The Functional Breakdown Structure (FBS) and Its Relationship to Life Cycle Cost  

NASA Technical Reports Server (NTRS)

The Functional Breakdown Structure (FBS) is a structured, modular breakdown of every function that must be addressed to perform a generic mission. It is also usable for any subset of the mission. Unlike a Work Breakdown Structure (WBS), the FBS is a function-oriented tree, not a product-oriented tree. The FBS details not products, but operations or activities that should be performed. The FBS is not tied to any particular architectural implementation because it is a listing of the needed functions, not the elements, of the architecture. The FBS for Space Transportation Systems provides a universal hierarchy of required functions, which include ground and space operations as well as infrastructure - it provides total visibility of the entire mission. By approaching the systems engineering problem from the functional view, instead of the element or hardware view, the SPST has created an exhaustive list of potential requirements which the architecture designers can use to evaluate the completeness of their designs. This is a new approach that will provide full accountability of all functions required to perform the planned mission. It serves as a giant check list to be sure that no functions are omitted, especially in the early architectural design phase. A significant characteristic of a FBS is that if architecture options are compared using this approach, then any missing or redundant elements of each option will be ' identified. Consequently, valid Life Cycle Costs (LCC) comparisons can be made. For example, one architecture option might not need a particular function while another option does. One option may have individual elements to perform each of three functions while another option needs only one element to perform the three functions. Once an architecture has been selected, the FBS will serve as a guide in development of the work breakdown structure, provide visibility of those technologies that need to be further developed to perform required functions, and help identify the personnel skills required to develop and operate the architecture. It also wifi allow the systems engineering activities to totally integrate each discipline to the maximum extent possible and optimize at the total system level, thus avoiding optimizing at the element level (stove-piping). In addition, it furnishes a framework that wifi help prevent over or under specifying requirements because all functions are identified and all elements are aligned to functions.

DeHoff, Bryan; Levack, Danie J. H.; Rhodes, Russell E.

2009-01-01

133

Acute bouts of assisted cycling improves cognitive and upper extremity movement functions in adolescents with down syndrome.  

PubMed

Abstract The aim of this study was to examine the effectiveness of 2 modes of exercise on cognitive and upper extremity movement functioning in adolescents with Down syndrome (DS). Nine participants randomly completed 3 interventions over 3 consecutive weeks. The interventions were: (a) voluntary cycling (VC), in which participants cycled at their self-selected pedaling rate; (b) assisted cycling (AC), in which the participants' voluntary pedaling rates were augmented with a motor to ensure the maintenance of 80 rpm; and (c) no cycling (NC), in which the participants sat and listened to music. Manual dexterity improved after AC, but not after VC or NC. Measures of cognitive function, including reaction time and cognitive planning, also improved after AC, but not after the other interventions. Future research will try to uncover the mechanisms involved in the behavioral improvements found after an acute bout of assisted cycling in adolescents with DS. PMID:24725111

Ringenbach, Shannon D R; Albert, Andrew R; Chen, Chih-Chia Jj; Alberts, Jay L

2014-04-01

134

Thermally Activated Persulfate Oxidation of Trichloroethylene (TCE) and 1,1,1Trichloroethane (TCA) in Aqueous Systems and Soil Slurries  

Microsoft Academic Search

Under thermally activated conditions (i.e., temperature of 40?99°C), there is considerable evidence that the persulfate anion () can be converted to a powerful oxidant known as the sulfate free radical (), which could be used in situ to destroy groundwater contaminants. In this laboratory study only limited trichloroethylene (TCE) degradation and no 1,1,1-trichloroethane (TCA) degradation was observed at 20°C. However,

Chen Ju Liang; Clifford J. Bruell; Michael C. Marley; Kenneth L. Sperry

2003-01-01

135

Regulation of the TCA cycle and the general amino acid permease by overflow metabolism in Rhizobium leguminosarum  

Microsoft Academic Search

Mutants of Rhizobium leguminosarum were selected that were altered in the uptake activity of the general amino acid permease (Aap). The main class of mutant maps to sud and suct), which are part of a gene cluster mdh-sucCDAB, which codes for malate dehydrogenase (mdh), succinyl-CoA synthetase (sucCD) and components of the 2-oxoglutarate dehydrogenase complex (sudB). Mutation of either SUCC or

David L. Walshaw; Adam Wilkinson; Mathius Mundy; Mary Smith; Philip S. Poole

1997-01-01

136

Q-site inhibitor induced ROS production of mitochondrial complex II is attenuated by TCA cycle dicarboxylates.  

PubMed

The impact of complex II (succinate:ubiquinone oxidoreductase) on the mitochondrial production of reactive oxygen species (ROS) has been underestimated for a long time. However, recent studies with intact mitochondria revealed that complex II can be a significant source of ROS. Using submitochondrial particles from bovine heart mitochondria as a system that allows the precise setting of substrate concentrations we could show that mammalian complex II produces ROS at subsaturating succinate concentrations in the presence of Q-site inhibitors like atpenin A5 or when a further downstream block of the respiratory chain occurred. Upon inhibition of the ubiquinone reductase activity, complex II produced about 75% hydrogen peroxide and 25% superoxide. ROS generation was attenuated by all dicarboxylates that are known to bind competitively to the substrate binding site of complex II, suggesting that the oxygen radicals are mainly generated by the unoccupied flavin site. Importantly, the ROS production induced by the Q-site inhibitor atpenin A5 was largely unaffected by the redox state of the Q pool and the activity of other respiratory chain complexes. Hence, complex II has to be considered as an independent source of mitochondrial ROS in physiology and pathophysiology. PMID:23800966

Siebels, Ilka; Dröse, Stefan

2013-10-01

137

Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina  

PubMed Central

Background Midkine is a small heparin binding growth factor expressed in numerous tissues during development. The unique midkine gene in mammals has two paralogs in zebrafish: midkine-a (mdka) and midkine-b (mdkb). In the zebrafish retina, during both larval development and adult photoreceptor regeneration, mdka is expressed in retinal stem and progenitor cells and functions as a molecular component of the retina’s stem cell niche. In this study, loss-of-function and conditional overexpression were used to investigate the function of Mdka in the retina of the embryonic zebrafish. Results The results show that during early retinal development Mdka functions to regulate cell cycle kinetics. Following targeted knockdown of Mdka synthesis, retinal progenitors cycle more slowly, and this results in microphthalmia, a diminished rate of cell cycle exit and a temporal delay of cell cycle exit and neuronal differentiation. In contrast, Mdka overexpression results in acceleration of the cell cycle and retinal overgrowth. Mdka gain-of-function, however, does not temporally advance cell cycle exit. Experiments to identify a potential Mdka signaling pathway show that Mdka functions upstream of the HLH regulatory protein, Id2a. Gene expression analysis shows Mdka regulates id2a expression, and co-injection of Mdka morpholinos and id2a mRNA rescues the Mdka loss-of-function phenotype. Conclusions These data show that in zebrafish, Mdka resides in a shared Id2a pathway to regulate cell cycle kinetics in retinal progenitors. This is the first study to demonstrate the function of Midkine during retinal development and adds Midkine to the list of growth factors that transcriptionally regulate Id proteins.

2012-01-01

138

Anti-hepatoma cells function of luteolin through inducing apoptosis and cell cycle arrest.  

PubMed

The aim of this study is to explore the apoptotic induction and cell cycle arrest function of luteolin on the liver cancer cells and the related mechanism. The liver cancer cell line SMMC-7721, BEL-7402, and normal liver cells HL-7702 were treated with different concentrations of luteolin. Cell proliferation ability was tested. Morphological changes of the apoptotic cells were observed under inverted fluorescence microscope after Hoechst33342 staining. We investigated the effect of luteolin on cell cycling and apoptosis with flow cytometry. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Caspases-3 and Bcl-2 family proteins expression were analyzed by real-time PCR. Cell proliferation of SMMC-7721 and BEL-7402 were inhibited by luteolin, and the inhibition was dose-time-dependent. Luteolin could arrest the cells at G1/S stage, reduce mitochondrial membrane potential, and induce higher apoptosis rate and the typical apoptotic morphological changes of the liver carcinoma cells. Q-RT-PCR results also showed that luteolin increased Bax and caspase-3 expression significantly and upregulated Bcl-2 expression in a dose-dependent manner in liver carcinoma cells. However, the normal liver cells HL-7702 was almost not affected by luteolin treatment. Luteolin can inhibit SMMC-7721 and BEL-7402 cell proliferation in a time- and dose-dependent manner. And the mechanism maybe through arresting cell cycle at phase G1/S, enhancing Bax level, reducing anti-apoptotic protein Bcl-2 level, resulting in activating caspase-3 enzyme and decrease of mitochondrial membrane potential, and finally leading to cell apoptosis. PMID:24287949

Ding, Shixiong; Hu, Airong; Hu, Yaoren; Ma, Jianbo; Weng, Pengjian; Dai, Jinhua

2014-04-01

139

LIMD1 antagonizes E2F1 activity and cell cycle progression by enhancing Rb function in cancer cells.  

PubMed

Tumour suppressor genes restrain inappropriate cell growth and division, as well as stimulate cell death to maintain tissue homeostasis. Loss of function leads to abnormal cellular behaviour, including hyperproliferation of cell and perturbation of cell cycle regulation. LIMD1 is a tumour suppressor gene located at chromosome 3p21.3, a region commonly deleted in many solid malignancies. LIMD1 interacts with retinoblastoma (Rb) and is involved in Rb-mediated downregulation of E2F1-target genes. However, the role of LIMD1 in cell cycle regulation remains unclear. We propose that LIMD1 induces cell cycle arrest, utilising Rb-E2F1 axis, and show that ectopic expression of LIMD1 in A549 cells results in hypo-phosphorylation that potentiates Rb function, which correlates with downregulation of E2F1. In agreement with these observations, LIMD1 overexpression retards cell cycle progression and blocks S-phase entry, as cells accumulate in G0/G1 phase and have reduced incorporation of BrdU. Most significantly, LIMD1-dependent effects on Rb function and cell cycle are reversed on depletion of endogenous LIMD1, underscoring its centrality in Rb-mediated cell cycle regulation. Hence, our findings provide new insight into cell cycle control by Rb-LIMD1 nexus. PMID:24523249

Mayank, Adarsh K; Sharma, Shipra; Deshwal, Ravi K; Lal, Sunil K

2014-07-01

140

The N cycle in Earth subsurface. Reactivity of functional genes to anthropogenic CO2 injections.  

NASA Astrophysics Data System (ADS)

The Nitrogen cycle has been widely studied in surface ecosystems, due to the importance of this nutrient for the organisms' development, and to the impact in the environment of most of the N forms, many of them being considered pollutants. However, little is known about the importance of the N-related metabolisms in subsurface systems now recognized to host diverse and active microbial life. In this study, we have periodically sampled the subsurface aquifers of the Icelandic pilot site for CO2 storage associated with the geothermal plant of Hellisheidi (operated by Reykjavik Energy; http://www.or.is/en/projects/carbfix). With the aim of understanding the dynamics of N-cycle in the subsurface, and its reactivity to CO2 injections, we quantified through qPCR the functional genes amoA (archaea), amoA (bacteria), nirK, nirS, nosZ, nifH, and the 16SrRNA genes of the anammox, total archaea and total bacteria. The 16SrRNA gene quantification provided values of around 107 gene copies/l at non injection periods. CO2 injection caused first a slight decrease probably due to pH decrease or toxicity by oxygen contamination during the injections. Two months after injection, the copy numbers increased up to 109 gene copies/l, and slowly returned to pre-injection values. The archaeal 16S rDNA copy numbers showed a similar reaction, with higher toxicity effects, and a lower increase afterwards. Due to the high reactivity of the microbial populations to CO2 injections, all the N cycle quantifications were related to the total 16S rDNA copies for normalization. Nitrifying genes (amoA) were mainly represented by the ammonia oxidizing archaea, and were apparently not affected by CO2 injections. Anammox bacteria were present in a very low percentage, and the obtained copy numbers tended to decrease after the injection. These results were surprising due to the autotrophic character of ammonia oxidizers, but could be explained by a competitive exclusion. On the contrary, N-fixation (nifH) was stimulated by the injections, doubling their relative abundance in relation to bacteria 16S rDNA copy numbers, supplying the N requirements of new biomass formed by autotrophic CO2 fixation. Finally, denitrifying bacteria (nirK, nirS and nosZ) showed a higher seasonal variation, but were positively stimulated by the CO2 injections. This process can be autotrophic in some species, using directly the injected CO2 as C source. Altogether the results suggest a high response of the N cycle to the CO2 injections, and its potential contribution to the formation of new biomass and C fixation. We provide evidences for the importance of the N cycle on the subsurface and its reactivity to CO2 injections, being therefore important the consideration of this cycle in CO2 storage modelling.

Trias, Rosalia; Gérard, Emmanuelle; Le Campion, Paul; Gíslason, Sigurður R.; Aradóttir, Edda S.; Alfreðsson, Helgui A.; Mesfin, Kiflom G.; Snæbjörnsdóttir, Sandra Ó.; Ménez, Bénédicte

2014-05-01

141

A central role for the peroxisomal membrane in glyoxylate cycle function.  

PubMed

The glyoxylate cycle provides the means to convert C2-units to C4-precursors for biosynthesis, allowing growth on fatty acids and C2-compounds. The conventional view that the glyoxylate cycle is contained within peroxisomes in fungi and plants is no longer valid. Glyoxylate cycle enzymes are located both inside and outside the peroxisome. Thus, the operation of the glyoxylate cycle requires transport of several intermediates across the peroxisomal membrane. Glyoxylate cycle progression is also dependent upon mitochondrial metabolism. An understanding of the operation and regulation of the glyoxylate cycle, and its integration with cellular metabolism, will require further investigation of the participating metabolite transporters in the peroxisomal membrane. PMID:17055076

Kunze, Markus; Pracharoenwattana, Itsara; Smith, Steven M; Hartig, Andreas

2006-12-01

142

Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1  

PubMed Central

Tumor cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. However, how tumor cycling hypoxia impacts chemotherapy is unclear. In the present study, we explored the impact and the mechanism of cycling hypoxia on tumor microenvironment-mediated chemoresistance. Hoechst 33342 staining and hypoxia-inducible factor–1 (HIF-1) activation labeling together with immunofluorescence imaging and fluorescence-activated cell sorting were used to isolate hypoxic tumor subpopulations from human glioblastoma xenografts. ABCB1 expression, P-glycoprotein function, and chemosensitivity in tumor cells derived from human glioblastoma xenografts or in vitro cycling hypoxic stress-treated glioblastoma cells were determined using Western blot analysis, drug accumulation and efflux assays, and MTT assay, respectively. ABCB1 expression and P-glycoprotein function were upregulated under cycling hypoxia in glioblastoma cells concomitant with decreased responses to doxorubicin and BCNU. However, ABCB1 knockdown inhibited these effects. Moreover, immunofluorescence imaging and flow cytometric analysis for ABCB1, HIF-1 activation, and Hoechst 3342 in glioblastoma revealed highly localized ABCB1 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion in the solid tumor microenvironment. The cycling hypoxic tumor cells derived from glioblastoma xenografts exhibited higher ABCB1 expression, P-glycoprotein function, and chemoresistance, compared with chronic hypoxic and normoxic cells. Tumor-bearing mice that received YC-1, an HIF-1? inhibitor, exhibited suppressed tumor microenvironment-induced ABCB1 induction and enhanced survival rate in BCNU chemotherapy. Cycling hypoxia plays a vital role in tumor microenvironment-mediated chemoresistance through the HIF-1–dependent induction of ABCB1. HIF-1 blockade before and concurrent with chemotherapy could suppress cycling hypoxia-induced chemoresistance.

Chou, Chii-Wen; Wang, Chi-Chung; Wu, Chung-Pu; Lin, Yu-Jung; Lee, Yu-Chun; Cheng, Ya-Wen; Hsieh, Chia-Hung

2012-01-01

143

A novel method to identify cooperative functional modules: study of module coordination in the Saccharomyces cerevisiae cell cycle  

PubMed Central

Background Identifying key components in biological processes and their associations is critical for deciphering cellular functions. Recently, numerous gene expression and molecular interaction experiments have been reported in Saccharomyces cerevisiae, and these have enabled systematic studies. Although a number of approaches have been used to predict gene functions and interactions, tools that analyze the essential coordination of functional components in cellular processes still need to be developed. Results In this work, we present a new approach to study the cooperation of functional modules (sets of functionally related genes) in a specific cellular process. A cooperative module pair is defined as two modules that significantly cooperate with certain functional genes in a cellular process. This method identifies cooperative module pairs that significantly influence a cellular process and the correlated genes and interactions that are essential to that process. Using the yeast cell cycle as an example, we identified 101 cooperative module associations among 82 modules, and importantly, we established a cell cycle-specific cooperative module network. Most of the identified module pairs cover cooperative pathways and components essential to the cell cycle. We found that 14, 36, 18, 15, and 20 cooperative module pairs significantly cooperate with genes regulated in early G1, late G1, S, G2, and M phase, respectively. Fifty-nine module pairs that correlate with Cdc28 and other essential regulators were also identified. These results are consistent with previous studies and demonstrate that our methodology is effective for studying cooperative mechanisms in the cell cycle. Conclusions In this work, we propose a new approach to identifying condition-related cooperative interactions, and importantly, we establish a cell cycle-specific cooperation module network. These results provide a global view of the cell cycle and the method can be used to discover the dynamic coordination properties of functional components in other cellular processes.

2011-01-01

144

Targeted disruption of the murine retinal dehydrogenase gene Rdh12 does not limit visual cycle function.  

PubMed

RDH12 codes for a member of the family of short-chain alcohol dehydrogenases/reductases proposed to function in the visual cycle that supplies the chromophore 11-cis retinal to photoreceptor cells. Mutations in RDH12 cause severe and progressive childhood onset autosomal-recessive retinal dystrophy, including Leber congenital amaurosis. We generated Rdh12 knockout mice, which exhibited grossly normal retinal histology at 10 months of age. Levels of all-trans and 11-cis retinoids in dark- and light-adapted animals and scotopic and photopic electroretinogram (ERG) responses were similar to those for the wild type, as was recovery of the ERG response following bleaching, for animals matched for an Rpe65 polymorphism (p.L450M). Lipid peroxidation products and other measures of oxidative stress did not appear to be elevated in Rdh12(-/-) animals. RDH12 was localized to photoreceptor inner segments and the outer nuclear layer in both mouse and human retinas by immunohistochemistry. The present findings, together with those of earlier studies showing only minor functional deficits in mice deficient for Rdh5, Rdh8, or Rdh11, suggest that the activity of any one isoform is not rate limiting in the visual response. PMID:17130236

Kurth, Ingo; Thompson, Debra A; Rüther, Klaus; Feathers, Kecia L; Chrispell, Jared D; Schroth, Jana; McHenry, Christina L; Schweizer, Michaela; Skosyrski, Sergej; Gal, Andreas; Hübner, Christian A

2007-02-01

145

Glucocorticoid receptor function regulated by coordinated action of the hsp90 and hsp70 chaperone cycles.  

PubMed

The glucocorticoid receptor (GR), like many signaling proteins, depends on the Hsp90 molecular chaperone for in vivo function. Although Hsp90 is required for ligand binding in vivo, purified apo GR is capable of binding ligand with no enhancement from Hsp90. We reveal that Hsp70, known to facilitate client delivery to Hsp90, inactivates GR through partial unfolding, whereas Hsp90 reverses this inactivation. Full recovery of ligand binding requires ATP hydrolysis on Hsp90 and the Hop and p23 cochaperones. Surprisingly, Hsp90 ATP hydrolysis appears to regulate client transfer from Hsp70, likely through a coupling of the two chaperone's ATP cycles. Such coupling is embodied in contacts between Hsp90 and Hsp70 in the GR:Hsp70:Hsp90:Hop complex imaged by cryoelectron microscopy. Whereas GR released from Hsp70 is aggregation prone, release from Hsp90 protects GR from aggregation and enhances its ligand affinity. Together, this illustrates how coordinated chaperone interactions can enhance stability, function, and regulation. PMID:24949977

Kirschke, Elaine; Goswami, Devrishi; Southworth, Daniel; Griffin, Patrick R; Agard, David A

2014-06-19

146

The iterated Carmichael l-function and the number of cycles of the power generator  

NASA Astrophysics Data System (ADS)

Iteration of the modular l-th power function f(x) = x^l (mod n) provides a common pseudorandom number generator (known as the Blum-Blum-Shub generator when l=2). The period of this pseudorandom number generator is closely related to \\lambda(\\lambda(n)), where \\lambda(n) denotes Carmichael's function, namely the maximal multiplicative order of any integer modulo n. In this paper, we show that for almost all n, the size of \\lambda(\\lambda(n)) is n/exp((1+o(1))(log log n)^2 log log log n). We conjecture an analogous formula for the k-th iterate of \\lambda. We deduce that for almost all n, the psuedorandom number generator described above has at least exp((1+o(1))(log log n)^2 log log log n) disjoint cycles. In addition, we show that this expression is accurate for almost all n under the assumption of the Generalized Riemann Hypothesis for Kummerian fields. We also consider the number of iterations of \\lambda it takes to reduce an integer n to 1, proving that this number is less than (1+o(1))(log log n)/log 2 infinitely often and speculating that log log n is the true order of magnitude almost always.

Martin, Greg; Pomerance, Carl

147

Ingestion of sodium plus water improves cardiovascular function and performance during dehydrating cycling in the heat.  

PubMed

We studied if salt and water ingestion alleviates the physiological strain caused by dehydrating exercise in the heat. Ten trained male cyclists (VO2max?: 60 ± 7 mL/kg/min) completed three randomized trials in a hot-dry environment (33 °C, 30% rh, 2.5 m/s airflow). Ninety minutes before the exercise, participants ingested 10 mL of water/kg body mass either alone (CON trial) or with salt to result in concentrations of 82 or 164 mM Na(+) (ModNa(+) or HighNa(+) trial, respectively). Then, participants cycled at 63% of VO2 m ? a x for 120 min immediately followed by a time-trial. After 120 min of exercise, the reduction in plasma volume was lessened with ModNa(+) and HighNa(+) trials (-11.9 ± 2.1 and -9.8 ± 4.2%) in comparison with CON (-16.4 ± 3.2%; P < 0.05). However, heat accumulation or dissipation (forearm skin blood flow and sweat rate) were not improved by salt ingestion. In contrast, both salt trials maintained cardiac output (? 1.3 ± 1.4 L/min; P < 0.05) and stroke volume (? 10 ± 11 mL/beat; P < 0.05) above CON after 120 min of exercise. Furthermore, the salt trials equally improved time-trial performance by 7.4% above CON (? 289 ± 42 vs 269 ± 50 W, respectively; P < 0.05). Our data suggest that pre-exercise ingestion of salt plus water maintains higher plasma volume during dehydrating exercise in the heat without thermoregulatory effects. However, it maintains cardiovascular function and improves cycling performance. PMID:23253191

Hamouti, N; Fernández-Elías, V E; Ortega, J F; Mora-Rodriguez, R

2014-06-01

148

Potential Abiotic Functions of Root Exudates in Rhizosphere Cycling of Soil Organic Matter  

NASA Astrophysics Data System (ADS)

Carbon cycling in the rhizosphere is a nexus of biophysical interactions between plant roots, microorganisms and the soil organo-mineral matrix. Plant roots are the primary source of C in mineral horizons and can significantly accelerate the rate of soil organic matter mineralization in rhizosphere soils. While a portion of this acceleration results from stimulation of microbial enzymatic capacities (the 'priming effect') - abiotic responses also play a significant role in rhizosphere cycling of soil organic matter (SOM). For example, exudate-stimulated mobilization and dissolution of metal species may release previously complexed SOM, or could affect Fe mobility via redox changes associated with microbially-driven O2 depletion. We have investigated the abiotic response of rhizosphere microenvironments, using additions of several 13C-enriched low molecular weight (LMW) root exudates and 13C-plant detritus to controlled microcosms. We hypothesized that certain abiotic effects are triggered by specific exudate compounds and that the magnitude of the effect depends on the soil physiochemical properties. Using a combination of microsensor measurements, solid-phase extractions, X-ray and IR spectroscopy, we measured how root exudates differ in their potential to create reducing microenvironments, alter metal chemisty and mineralogy, and influence the availability of SOM in the rhizosphere. High resolution X-ray microscopy (STXM) and secondary ion mass spectrometry (NanoSIMS) analyses illustrate the physical fate of the added isotope tracers in both pore water and on mineral surfaces. Our results suggest that certain root exudates facilitate abiotic reactions that increase the pool of bioavailable SOM and stimulate its microbial decomposition in the rhizosphere. In particular, the contrasting ecological functions of LMW organic acids and simple sugars in facilitating SOM breakdown in the rhizosphere will be discussed.

Pett-Ridge, J.; Keiluweit, M.; Bougoure, J.; Kleber, M.; Nico, P. S.

2012-12-01

149

Atherosclerosis and cardiac function assessment in low-density lipoprotein receptor-deficient mice undergoing body weight cycling.  

PubMed

Background:Obesity has become an epidemic in many countries and is supporting a billion dollar industry involved in promoting weight loss through diet, exercise and surgical procedures. Because of difficulties in maintaining body weight reduction, a pattern of weight cycling often occurs (so called 'yo-yo' dieting) that may result in deleterious outcomes to health. There is controversy about cardiovascular benefits of yo-yo dieting, and an animal model is needed to better understand the contributions of major diet and body weight changes on heart and vascular functions. Our purpose is to determine the effects of weight cycling on cardiac function and atherosclerosis development in a mouse model.Methods:We used low-density lipoprotein receptor-deficient mice due to their sensitivity to metabolic syndrome and cardiovascular diseases when fed high-fat diets. Alternating ad libitum feeding of high-fat and low-fat (rodent chow) diets was used to instigate weight cycling during a 29-week period. Glucose tolerance and insulin sensitivity tests were done at 22 and 24 weeks, echocardiograms at 25 weeks and atherosclerosis and plasma lipoproteins assessed at 29 weeks.Results:Mice subjected to weight cycling showed improvements in glucose homeostasis during the weight loss cycle. Weight-cycled mice showed a reduction in the severity of atherosclerosis as compared with high-fat diet-fed mice. However, atherosclerosis still persisted in weight-cycled mice as compared with mice fed rodent chow. Cardiac function was impaired in weight-cycled mice and matched with that of mice fed only the high-fat diet.Conclusion:This model provides an initial structure in which to begin detailed studies of diet, calorie restriction and surgical modifications on energy balance and metabolic diseases. This model also shows differential effects of yo-yo dieting on metabolic syndrome and cardiovascular diseases. PMID:23797386

McMillen, T S; Minami, E; Leboeuf, R C

2013-01-01

150

Atherosclerosis and cardiac function assessment in low-density lipoprotein receptor-deficient mice undergoing body weight cycling  

PubMed Central

Background: Obesity has become an epidemic in many countries and is supporting a billion dollar industry involved in promoting weight loss through diet, exercise and surgical procedures. Because of difficulties in maintaining body weight reduction, a pattern of weight cycling often occurs (so called ‘yo-yo' dieting) that may result in deleterious outcomes to health. There is controversy about cardiovascular benefits of yo-yo dieting, and an animal model is needed to better understand the contributions of major diet and body weight changes on heart and vascular functions. Our purpose is to determine the effects of weight cycling on cardiac function and atherosclerosis development in a mouse model. Methods: We used low-density lipoprotein receptor-deficient mice due to their sensitivity to metabolic syndrome and cardiovascular diseases when fed high-fat diets. Alternating ad libitum feeding of high-fat and low-fat (rodent chow) diets was used to instigate weight cycling during a 29-week period. Glucose tolerance and insulin sensitivity tests were done at 22 and 24 weeks, echocardiograms at 25 weeks and atherosclerosis and plasma lipoproteins assessed at 29 weeks. Results: Mice subjected to weight cycling showed improvements in glucose homeostasis during the weight loss cycle. Weight-cycled mice showed a reduction in the severity of atherosclerosis as compared with high-fat diet-fed mice. However, atherosclerosis still persisted in weight-cycled mice as compared with mice fed rodent chow. Cardiac function was impaired in weight-cycled mice and matched with that of mice fed only the high-fat diet. Conclusion: This model provides an initial structure in which to begin detailed studies of diet, calorie restriction and surgical modifications on energy balance and metabolic diseases. This model also shows differential effects of yo-yo dieting on metabolic syndrome and cardiovascular diseases.

McMillen, T S; Minami, E; LeBoeuf, R C

2013-01-01

151

Enhanced connexin 43 expression delays intra-mitoitc duration and cell cycle traverse independently of gap junction channel function  

PubMed Central

Connexins (Cx) and gap junction (GJ) mediated communication has been linked with the regulation of cell cycle traverse. However, it is not clear whether Cx expression or GJ channel function are the key mediators in this process or at what stage this regulation may occur. We therefore tested the hypothesis that enhanced Cx expression could alter the rate of cell cycle traverse independently of GJ channel function. Sodium butyrate (NaBu) or anti-arrhythmic peptide (AAP10) were used to enhance Cx expression in HeLa cells stably expressing Cx43 (HeLa-43) and primary cultures of human fibroblasts (HFF) that predominantly express Cx43. To reduce GJ mediated communication, 18?-glycyrrhetinic acid (GA) was used. In HeLa-43 and HFF cells, NaBu and AAP10 enhanced Cx43 expression and increased channel function, while GA reduced GJ mediated communication but did not significantly alter Cx43 expression levels. Timelapse microscopy and flow cytometry of HeLa-WT (wild type, Cx deficient) and HeLa-43 cells dissected cell cycle traverse and enabled measurements of intra-mitotic time and determined levels of G1 arrest. Enhanced Cx43 expression increased mitotic durations corresponding with a G1 delay in cell cycle, which was linked to an increase in expression of the cell cycle inhibitor p21waf1/cip1 in both HeLa-43 and HFF cells. Reductions in Cx43 channel function did not abrogate these responses, indicating that GJ channel function was not a critical factor in reducing cell proliferation in either cell type. We conclude that enhanced Cx43 expression and not GJ mediated communication, is involved in regulating cell cycle traverse.

Johnstone, Scott R.; Best, Angela K.; Wright, Catherine S.; Isakson, Brant E.; Errington, Rachel J.; Martin, Patricia E.

2011-01-01

152

The tricarboxylic acid cycle in Shewanella oneidensis is independent of Fur and RyhB control  

PubMed Central

Background It is well established in E. coli and Vibrio cholerae that strains harboring mutations in the ferric uptake regulator gene (fur) are unable to utilize tricarboxylic acid (TCA) compounds, due to the down-regulation of key TCA cycle enzymes, such as AcnA and SdhABCD. This down-regulation is mediated by a Fur-regulated small regulatory RNA named RyhB. It is unclear in the ?-proteobacterium S. oneidensis whether TCA is also regulated by Fur and RyhB. Results In the present study, we showed that a fur deletion mutant of S. oneidensis could utilize TCA compounds. Consistently, expression of the TCA cycle genes acnA and sdhA was not down-regulated in the mutant. To explore this observation further, we identified a ryhB gene in Shewanella species and experimentally demonstrated the gene expression. Further experiments suggested that RyhB was up-regulated in fur mutant, but that AcnA and SdhA were not controlled by RyhB. Conclusions These cumulative results delineate an important difference of the Fur-RyhB regulatory cycle between S. oneidensis and other ?-proteobacteria. This work represents a step forward for understanding the unique regulation in S. oneidensis.

2010-01-01

153

Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.  

PubMed

Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role. PMID:24769512

Senthamizhselvan, Oomaidurai; Manivannan, Jeganathan; Silambarasan, Thangarasu; Raja, Boobalan

2014-08-01

154

A SET-domain-independent role of WRAD complex in cell-cycle regulatory function of mixed lineage leukemia.  

PubMed

MLL, the trithorax ortholog, is a well-characterized histone 3 lysine 4 methyltransferase that is crucial for proper regulation of the Hox genes during embryonic development. Chromosomal translocations, disrupting the Mll gene, lead to aggressive leukemia with poor prognosis. However, the functions of MLL in cellular processes like cell-cycle regulation are not well studied. Here we show that the MLL has a regulatory role during multiple phases of the cell cycle. RNAi-mediated knockdown reveals that MLL regulates S-phase progression and, proper segregation and cytokinesis during M phase. Using deletions and mutations, we narrow the cell-cycle regulatory role to the C subunit of MLL. Our analysis reveals that the transactivation domain and not the SET domain is important for the S-phase function of MLL. Surprisingly, disruption of MLL-WRAD interaction is sufficient to disrupt proper mitotic progression. These mitotic functions of WRAD are independent of SET domain of MLL and, therefore, define a new role of WRAD in subset of MLL functions. Finally, we address the overlapping and unique roles of the different SET family members in the cell cycle. PMID:24880690

Ali, Aamir; Veeranki, Sailaja Naga; Tyagi, Shweta

2014-08-01

155

A SET-domain-independent role of WRAD complex in cell-cycle regulatory function of mixed lineage leukemia  

PubMed Central

MLL, the trithorax ortholog, is a well-characterized histone 3 lysine 4 methyltransferase that is crucial for proper regulation of the Hox genes during embryonic development. Chromosomal translocations, disrupting the Mll gene, lead to aggressive leukemia with poor prognosis. However, the functions of MLL in cellular processes like cell-cycle regulation are not well studied. Here we show that the MLL has a regulatory role during multiple phases of the cell cycle. RNAi-mediated knockdown reveals that MLL regulates S-phase progression and, proper segregation and cytokinesis during M phase. Using deletions and mutations, we narrow the cell-cycle regulatory role to the C subunit of MLL. Our analysis reveals that the transactivation domain and not the SET domain is important for the S-phase function of MLL. Surprisingly, disruption of MLL–WRAD interaction is sufficient to disrupt proper mitotic progression. These mitotic functions of WRAD are independent of SET domain of MLL and, therefore, define a new role of WRAD in subset of MLL functions. Finally, we address the overlapping and unique roles of the different SET family members in the cell cycle.

Ali, Aamir; Veeranki, Sailaja Naga; Tyagi, Shweta

2014-01-01

156

Ovarian Cycle and Effect of Social Changes on Adrenal and Ovarian Function in Pygathrix nemaeus  

Microsoft Academic Search

To assist captive breeding of the endangered red-shanked douc langur (Pygathrix nemaeus), basic knowledge on female reproductive physiology is important. We aimed 1) to characterize the pattern of fecal estrogens and progestogens during the ovarian cycle and 2) to use the information to provide reliable data on ovarian cycle characteristics. Moreover, we examined the potential impact of a change in

Michael Heistermann; Christelle Ademmer; Werner Kaumanns

2004-01-01

157

Influence of Tai Chi exercise cycle on the senile respiratory and cardiovascular circulatory function  

PubMed Central

Objective: Observe the improvement effect of different cycles of Tai Chi exercise on the senile respiratory and cardiovascular circulatory function. Methods: Select 180 elderly men who don’t usually do the fitness exercise and then ask them to do Tai Chi exercise. Test their related indicators respectively prior to exercise and upon exercise for 3 months, 6 months and 12 months. ? The cardiac pump function indicator: “Stroke Volume”, “Ejection Fraction” and “Heart Rate”; ? Rheoencephalogram (REG) indicator: “Inflow time”, “Wave Amplitude”; ? Pulmonary ventilation indicator: “Vital Capacity” (VC), “Maximum Minute Ventilation” (MMV). Results: ? Compared with the indicators before exercise, each indicator has no significant difference after 3 months of exercise and a part of indicators are improved after 6 months of exercise, but most indicators have no significant differences; ? After 12 months of the exercise, compared with those indicators before exercise, the tested indicators are obviously improved. Specific data indicates that stroke volume (mL) is increased to 71.82 ± 10.93 from 66.21 ± 11.35 and the ejection fraction (%) is improved to 67.89 ± 4.94 from 60.54 ± 5.02, but the heart rate (times/min) is reduced to 67.15 ± 8.39 from 76.62 ± 8.40, mean P<0.05; inflow time (s) is shortened to 0.13 ± 0.04 from 0.17 ± 0.05; the amplitude (?) is increased to 1.19 ± 0.23 from 0.97 ± 0.21 before exercise and mean P<0.05; the vital capacity (L) is increased to 3.57 ± 1.39 from 2.84 ± 0.32; maximum minute ventilation (L/min) is improved to 117.25 ± 14.86 from 97.26 ± 14.71, mean P<0.05. Conclusion: The short-term Tai Chi exercise that is less than six months the following 6 months has no significant effect on the senile respiratory and cardiovascular circulatory function, however, with the longer exercise duration, after 12 months’ exercise, it can significantly improve the effect.

Song, Qing-Hua; Xu, Rong-Mei; Shen, Guo-Qing; Zhang, Quan-Hai; Ma, Ming; Zhao, Xin-Ping; Guo, Yan-Hua; Wang, Yi

2014-01-01

158

Spatial distribution of cellular function: the partitioning of proteins between mitochondria and the nucleus in MCF7 breast cancer cells.  

PubMed

Concurrent proteomics analysis of the nuclei and mitochondria of MCF7 breast cancer cells identified 985 proteins (40% of all detected proteins) present in both organelles. Numerous proteins from all five complexes involved in oxidative phosphorylation (e.g., NDUFA5, NDUFB10, NDUFS1, NDUF2, SDHA, UQRB, UQRC2, UQCRH, COX5A, COX5B, MT-CO2, ATP5A1, ATP5B, ATP5H, etc.), from the TCA-cycle (DLST, IDH2, IDH3A, OGDH, SUCLAG2, etc.), and from glycolysis (ALDOA, ENO1, FBP1, GPI, PGK1, TALDO1, etc.) were distributed to both the nucleus and mitochondria. In contrast, proteins involved in nuclear/mitochondrial RNA processing/translation and Ras/Rab signaling showed different partitioning patterns. The identity of the OxPhos, TCA-cycle, and glycolysis proteins distributed to both the nucleus and mitochondria provides evidence for spatio-functional integration of these processes over the two different subcellular organelles. We suggest that there are unrecognized aspects of functional coordination between the nucleus and mitochondria, that integration of core functional processes via wide subcellular distribution of constituent proteins is a common characteristic of cells, and that subcellular spatial integration of function may be a vital aspect of cancer. PMID:23051583

Qattan, Amal T; Radulovic, Marko; Crawford, Mark; Godovac-Zimmermann, Jasminka

2012-12-01

159

Effect of biofeedback cycling training on functional recovery and walking ability of lower extremity in patients with stroke.  

PubMed

This study aimed to investigate the effectiveness of biofeedback cycling training on lower limb functional recovery, walking endurance, and walking speed for patients with chronic stroke. Thirty-one patients with stroke (stroke onset >3 months) were randomly assigned into two groups using a crossover design. One group (N = 16; mean: 53.6 ± 10.3 years) underwent conventional rehabilitation and cycling training (30 minutes/time, 5 times per week for 4 weeks), followed by only conventional rehabilitation for another 4 weeks. The other group (N = 15; mean: 54.5 ± 8.0 years) underwent the same training in reverse order. The bike used in this biofeedback cycling training was the MOTOmed viva2 Movement Trainer. Outcome measures included the lower extremity subscale of Fugl-Meyer assessment (LE-FMA), the 6-minute walk test (6MWT), the 10-meter walk test (10MWT), and the modified Ashworth scale (MAS). All participants were assessed at the beginning of the study, at the end of the 4(th) week, and at the end of the 8(th) week. Thirty participants completed the study, including the cycling training interventions and all assessments. The results showed that improvements in the period with cycling training were significantly better than the noncycling period in the LE-FMA (p < 0.05), 6MWT (p < 0.001), 10MWT (p < 0.001), and MAS (p < 0.001) scores. No significant carryover effects were observed. The improvements on outcome measures were significantly different between the cycling period and the noncycling period after adjusting for potential confounding factors in the multivariate analysis of variance (p < 0.001). The study result indicates that the additional 4-week biofeedback cycling training could lead to improved LE functional recovery, walking endurance, and speed for patients with chronic stroke. PMID:24388057

Yang, Huei-Ching; Lee, Chia-Ling; Lin, Roxane; Hsu, Miao-Ju; Chen, Chia-Hsin; Lin, Jau-Hong; Lo, Sing Kai

2014-01-01

160

Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial  

PubMed Central

Introduction Intensive care-acquired weakness is a common problem, leads to significant impairment in physical functioning and muscle strength, and is prevalent in individuals with sepsis. Early rehabilitation has been shown to be safe and feasible; however, commencement is often delayed due to a patient's inability to co-operate. An intervention that begins early in an intensive care unit (ICU) admission without the need for patient volition may be beneficial in attenuating muscle wasting. The eRiCC (early rehabilitation in critical care) trial will investigate the effectiveness of functional electrical stimulation-assisted cycling and cycling alone, compared to standard care, in individuals with sepsis. Methods and analysis This is a single centre randomised controlled trial. Participants (n=80) aged ?18?years, with a diagnosis of sepsis or severe sepsis, who are expected to be mechanically ventilated for ?48?h and remain in the intensive care ?4?days will be randomised within 72?h of admission to (1) standard care or (2) intervention where participants will receive functional electrical muscle stimulation-assisted supine cycling on one leg while the other leg undergoes cycling alone. Primary outcome measures include: muscle mass (quadriceps ultrasonography; bioelectrical impedance spectroscopy); muscle strength (Medical Research Council Scale; hand-held dynamometry) and physical function (Physical Function in Intensive Care Test; Functional Status Score in intensive care; 6?min walk test). Blinded outcome assessors will assess measures at baseline, weekly, at ICU discharge and acute hospital discharge. Secondary measures will be evaluated in a nested subgroup (n=20) and will consist of biochemical/histological analyses of collected muscle, urine and blood samples at baseline and at ICU discharge. Ethics and dissemination Ethics approval has been obtained from the relevant institution, and results will be published to inform clinical practice in the care of patients with sepsis to optimise rehabilitation and physical function outcomes. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12612000528853.

Parry, Selina M; Berney, Sue; Koopman, Rene; Bryant, Adam; El-Ansary, Doa; Puthucheary, Zudin; Hart, Nicholas; Warrillow, Stephen; Denehy, Linda

2012-01-01

161

Functional genes to assess nitrogen cycling and aromatic hydrocarbon degradation: primers and processing matter  

PubMed Central

Targeting sequencing to genes involved in key environmental processes, i.e., ecofunctional genes, provides an opportunity to sample nature's gene guilds to greater depth and help link community structure to process-level outcomes. Vastly different approaches have been implemented for sequence processing and, ultimately, for taxonomic placement of these gene reads. The overall quality of next generation sequence analysis of functional genes is dependent on multiple steps and assumptions of unknown diversity. To illustrate current issues surrounding amplicon read processing we provide examples for three ecofunctional gene groups. A combination of in silico, environmental and cultured strain sequences was used to test new primers targeting the dioxin and dibenzofuran degrading genes dxnA1, dbfA1, and carAa. The majority of obtained environmental sequences were classified into novel sequence clusters, illustrating the discovery value of the approach. For the nitrite reductase step in denitrification, the well-known nirK primers exhibited deficiencies in reference database coverage, illustrating the need to refine primer-binding sites and/or to design multiple primers, while nirS primers exhibited bias against five phyla. Amino acid-based OTU clustering of these two N-cycle genes from soil samples yielded only 114 unique nirK and 45 unique nirS genus-level groupings, likely a reflection of constricted primer coverage. Finally, supervised and non-supervised OTU analysis methods were compared using the nifH gene of nitrogen fixation, with generally similar outcomes, but the clustering (non-supervised) method yielded higher diversity estimates and stronger site-based differences. High throughput amplicon sequencing can provide inexpensive and rapid access to nature's related sequences by circumventing the culturing barrier, but each unique gene requires individual considerations in terms of primer design and sequence processing and classification.

Penton, C. Ryan; Johnson, Timothy A.; Quensen, John F.; Iwai, Shoko; Cole, James R.; Tiedje, James M.

2013-01-01

162

Stable isotope approaches for tracking C cycling and function in microbial communities  

NASA Astrophysics Data System (ADS)

Identifying the microorganisms responsible for specific processes in C cycling remains a major challenge in environmental microbiology, one that requires integration of multiple techniques. Stable isotope probing, or SIP, has come to represent a variety of powerful approaches that allow simultaneous identification of identity and function in microbial communities. Bulk methods such as DNA/RNA-SIP and PLFA-SIP are well developed and allow tracking of a multitude of C substrates (acetate, cellulose, CH4, CO2, and plant litter) into specific microbial consumers. However, to understand the spatio-temporal context of may key C transformations and microbial interactions, new imaging technologies are needed to analyze processes and properties of macromolecule complexes, microbes, plant root cells, soil (micro)aggregates, phytoplankton and marine snow as they undergoes formation and decomposition. New and sensitive in situ approaches include NanoSIMS single cell analysis, isotope arrays, and combinations of immuno- or FISH labeling with high resolution isotope imaging. Recent work illustrates how these powerful new techniques use targeted stable isotope probing to measure biological, physical and chemical processes and can be used in soil systems to study microbial mats or rhizosphere interactions. In both terrestrial and aquatic systems, they allow us to directly link C and other nutrient metabolism at the organismal level. Lastly, these new aproaches may be of great use in the study of trophic cascades and metabolic networks. While cross-feeding is often thought of as a confounding effect in SIP-type studies, with fine scale temporal sampling and FISH-SIMS analysis, we have the opportunity trace C flows through microbial foodwebs and to their eventual fate in stabilized organic-mineral complexes.

Pett-Ridge, J.

2008-12-01

163

A generalized harmonic function perturbation method for determining limit cycles and homoclinic orbits of Helmholtz—Duffing oscillator  

NASA Astrophysics Data System (ADS)

In this paper, a novel description of periodic solution and homoclinic orbit of undamped Helmholtz—Duffing oscillator is proposed via nonlinear time transformation. Based on this novel description, a generalized harmonic function perturbation method is presented to determine the limit cycles and homoclinic orbits of Helmholtz—Duffing oscillator with nonlinear damping. The amplitude of limit cycle and critical value of the homoclinic bifurcation parameter can be also predicted. To illustrate the accuracy of the present method, the solutions obtained in this paper are compared with those of Runge—Kutta method, which shows the method proposed in this paper is effective and feasible.

Li, Zhenbo; Tang, Jiashi; Cai, Ping

2013-10-01

164

Computational functions in biochemical reaction networks.  

PubMed Central

In prior work we demonstrated the implementation of logic gates, sequential computers (universal Turing machines), and parallel computers by means of the kinetics of chemical reaction mechanisms. In the present article we develop this subject further by first investigating the computational properties of several enzymatic (single and multiple) reaction mechanisms: we show their steady states are analogous to either Boolean or fuzzy logic gates. Nearly perfect digital function is obtained only in the regime in which the enzymes are saturated with their substrates. With these enzymatic gates, we construct combinational chemical networks that execute a given truth-table. The dynamic range of a network's output is strongly affected by "input/output matching" conditions among the internal gate elements. We find a simple mechanism, similar to the interconversion of fructose-6-phosphate between its two bisphosphate forms (fructose-1,6-bisphosphate and fructose-2,6-bisphosphate), that functions analogously to an AND gate. When the simple model is supplanted with one in which the enzyme rate laws are derived from experimental data, the steady state of the mechanism functions as an asymmetric fuzzy aggregation operator with properties akin to a fuzzy AND gate. The qualitative behavior of the mechanism does not change when situated within a large model of glycolysis/gluconeogenesis and the TCA cycle. The mechanism, in this case, switches the pathway's mode from glycolysis to gluconeogenesis in response to chemical signals of low blood glucose (cAMP) and abundant fuel for the TCA cycle (acetyl coenzyme A). Images FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 7 FIGURE 10 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16

Arkin, A; Ross, J

1994-01-01

165

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones  

Microsoft Academic Search

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex\\u000a hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym\\u000a generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and\\u000a midluteal cycle phase. The activation pattern in all

C. Konrad; A. Engelien; S. Schöning; P. Zwitserlood; A. Jansen; E. Pletziger; P. Beizai; A. Kersting; P. Ohrmann; E. Luders; R. R. Greb; W. Heindel; V. Arolt; H. Kugel

2008-01-01

166

Parasitic antenna loading measurements and comparison between shielded and unshielded antenna excitation during Alfven wave heating in TCA  

NASA Astrophysics Data System (ADS)

The authors present experimental measurements of the parasitic loading resulting from a radio-frequency (RF) Langmuir or sheath current which flows from an unshielded antenna to the scrape-off layer (SOL) during Alfven wave heating (AWH) in TCA. The measurements are of relevance to ion cyclotron resonance heating where RF currents drawn by either electrostatic screens or side limiters lead to parasitic loading and harmonic generation in the SOL. An experimental study of the plasma response to AWH after the installation of screens on the AWH antennas is also presented. The results demonstrate that the RF sheath current and some of the parasitic phenomena observed in the SOL during AWH with unshielded antennas are eliminated by screens. The plasma bulk response, however, is dominated by a large density rise which is unaffected by screens

Borg, G. G.; Joye, B.

1992-05-01

167

Functional Dissection of Caenorhabditis elegans CLK-2/TEL2 Cell Cycle Defects during Embryogenesis and Germline Development  

PubMed Central

CLK-2/TEL2 is essential for viability from yeasts to vertebrates, but its essential functions remain ill defined. CLK-2/TEL2 was initially implicated in telomere length regulation in budding yeast, but work in Caenorhabditis elegans has uncovered a function in DNA damage response signalling. Subsequently, DNA damage signalling defects associated with CLK-2/TEL2 have been confirmed in yeast and human cells. The CLK-2/TEL2 interaction with the ATM and ATR DNA damage sensor kinases and its requirement for their stability led to the proposal that CLK-2/TEL2 mutants might phenocopy ATM and/or ATR depletion. We use C. elegans to dissect developmental and cell cycle related roles of CLK-2. Temperature sensitive (ts) clk-2 mutants accumulate genomic instability and show a delay of embryonic cell cycle timing. This delay partially depends on the worm p53 homolog CEP-1 and is rescued by co-depletion of the DNA replication checkpoint proteins ATL-1 (C. elegans ATR) and CHK-1. In addition, clk-2 ts mutants show a spindle orientation defect in the eight cell stages that lead to major cell fate transitions. clk-2 deletion worms progress through embryogenesis and larval development by maternal rescue but become sterile and halt germ cell cycle progression. Unlike ATL-1 depleted germ cells, clk-2–null germ cells do not accumulate DNA double-strand breaks. Rather, clk-2 mutant germ cells arrest with duplicated centrosomes but without mitotic spindles in an early prophase like stage. This germ cell cycle arrest does not depend on cep-1, the DNA replication, or the spindle checkpoint. Our analysis shows that CLK-2 depletion does not phenocopy PIKK kinase depletion. Rather, we implicate CLK-2 in multiple developmental and cell cycle related processes and show that CLK-2 and ATR have antagonising functions during early C. elegans embryonic development.

Moser, Sandra C.; von Elsner, Sophie; Bussing, Ingo; Alpi, Arno; Schnabel, Ralf; Gartner, Anton

2009-01-01

168

The anti-apoptosis function of Bcl-2 can be genetically separated from its inhibitory effect on cell cycle entry.  

PubMed Central

The Bcl-2 family of proteins regulate apoptosis, some antagonizing cell death and others facilitating it. It has recently been demonstrated that Bcl-2 not only inhibits apoptosis but also restrains cell cycle entry. We show here that these two functions can be genetically dissociated. Mutation of a tyrosine residue within the conserved N-terminal BH4 region had no effect on the ability of Bcl-2 or its closest homologs to enhance cell survival and did not prevent heterodimerization with death-enhancing family members Bax, Bak, Bad and Bik. Neither did this mutation override the growth-inhibitory effect of p53. However, on stimulation with cytokine or serum, starved quiescent cells expressing the mutant proteins re-entered the cell cycle much faster than those expressing comparable levels of wild-type proteins. When wild-type and Y28 mutant Bcl-2 were co-expressed, the mutant was dominant. Although R-Ras p23 has been reported to bind to Bcl-2, no interaction was detectable in transfected cells and R-Ras p23 did not interfere with the ability of Bcl-2 to inhibit apoptosis or cell cycle entry. These observations provide evidence that the anti-apoptotic function of Bcl-2 is mechanistically distinct from its inhibitory influence on cell cycle entry.

Huang, D C; O'Reilly, L A; Strasser, A; Cory, S

1997-01-01

169

Fiat lux! Phylogeny and bioinformatics shed light on GABA functions in plants.  

PubMed

The non-protein amino acid ?-aminobutyric acid (GABA) accumulates in plants in response to a wide variety of environmental cues. Recent data point toward an involvement of GABA in tricarboxylic acid (TCA) cycle activity and respiration, especially in stressed roots. To gain further insights into potential GABA functions in plants, phylogenetic and bioinformatic approaches were undertaken. Phylogenetic reconstruction of the GABA transaminase (GABA-T) protein family revealed the monophyletic nature of plant GABA-Ts. However, this analysis also pointed to the common origin of several plant aminotransferases families, which were found more similar to plant GABA-Ts than yeast and human GABA-Ts. A computational analysis of AtGABA-T co-expressed genes was performed in roots and in stress conditions. This second approach uncovered a strong connection between GABA metabolism and glyoxylate cycle during stress. Both in silico analyses open new perspectives and hypotheses for GABA metabolic functions in plants. PMID:23518583

Renault, Hugues

2013-06-01

170

Li-Ion polymer cells thermal property changes as a function of cycle-life  

NASA Astrophysics Data System (ADS)

The impact of elevated temperature charge-discharge cycling on thermal conductivity (K-value) of Lithium Ion Polymer (LIP) cells of various chemistries from three different manufacturers was investigated. These included high voltage (Graphite/LiCoO2:3.0-4.35 V), wide voltage (Si:C/LiCoO2:2.7-4.35 V) and conventional (Graphite/LiCoO2:3.0-4.2 V) chemistries. Investigation results show limited variability within the in-plane and through-plane K-values for the fresh cells with graphite-based anodes from all three suppliers. After 500 cycles at 45 °C, in-plane and through-plane K-values of the high voltage cells reduced less vs. those for the wide voltage cells. Such results suggest that high temperature cycling could have a greater impact on thermal properties of Si:C cells than on the LIP cells with graphite (Gr) anode cells we tested. This difference is due to the excess swelling of Si:C-anode based cells vs. Gr-anode cells during cycling, especially at elevated temperatures. Thermal modeling is used to evaluate the impact of K-value changes, due to cycles at 45 °C, on the cells internal heat propagation under internal short circuit condition that leads to localized meltdown of the separator.

Maleki, Hossein; Wang, Hsin; Porter, Wally; Hallmark, Jerry

2014-10-01

171

Functional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis  

Microsoft Academic Search

Cell cycle-related kinase (CCRK) is a newly identified protein kinase homologous to Cdk7. We have previously shown that CCRK is a candidate oncogene in human glioblastoma. However, whether CCRK is a bona fide oncogene remains to be tested. The aim of this study was to investigate the role of CCRK in human colorectal cancer carcinogenesis. By Western blotting, we analysed

Xiaomeng An; Samuel S. Ng; Dan Xie; Yi-Xin Zeng; Johnny Sze; Jide Wang; Yang Chao Chen; Billy K. C. Chow; Gang Lu; Wai Sang Poon; Hsiang-fu Kung; Benjamin C. Y. Wong; Marie Chia-mi Lin

2010-01-01

172

Metabolite and isotopomer balancing in the analysis of metabolic cycles: II. Applications  

Microsoft Academic Search

In a previous paper (Klapa et al., 1999), we pre- sented a model for the analysis of isotopomer distribu- tions of the TCA cycle intermediates resulting from 13C (or 14C) labeling experiments. Results allow the rigorous determination of the degree of enrichment at specific carbon atoms of metabolites, of the molecular weight distribution of metabolite isotopomers, as well as of

Sung M. Park; Maria I. Klapa; Anthony J. Sinskey; Gregory Stephanopoulos

1999-01-01

173

Biostimulation induces syntrophic interactions that impact C, S and N cycling in a sediment microbial community  

SciTech Connect

Stimulation of subsurface microorganisms to induce reductive immobilization of metals is a promising approach for bioremediation, yet the overall microbial community response is typically poorly understood. Here we used community proteogenomics to test the hypothesis that excess input of acetate activates syntrophic interactions among autotrophs and heterotrophs. A flow-through sediment column was incubated in a groundwater well of an acetate-amended aquifer. Genomic sequences from the community recovered during microbial sulfate reduction were used to econstruct, de novo, near-complete genomes for Desulfobacter (Deltaproteobacteria) and relatives of Sulfurovum and Sulfurimonas (Epsilonproteobacteria), and Bacteroidetes. Partial genomes were obtained for Clostridiales (Firmicutes) and Desulfuromonadales-like Deltaproteobacteria. The majority of proteins identified by mass spectrometry corresponded to Desulfobacter-like species, and demonstrate the role of this organism in sulfate reduction (Dsr and APS), nitrogen-fixation (Nif) and acetate oxidation to CO2 during amendment. Results suggest less abundant Desulfuromonadales and Bacteroidetes also actively contributed to CO2 production via the TCA cycle. Proteomic data indicate that sulfide was partially re-oxidized by Epsilonproteobacteria through nitrate-dependent sulfide oxidation (using Nap, Nir, Nos, SQR and Sox), with CO2 fixed using the reverse TCA cycle. Modeling shows that this reaction was thermodynamically possible, and kinetically favorable relative to acetate-dependent denitrification. We conclude that high-levels of carbon amendment aimed to stimulate anaerobic heterotrophy led to carbon fixation in co-dependent chemoautotrophs. These results have implications for understanding complex ecosystem behavior, and show that high levels of organic carbon supplementation can expand the range of microbial functionalities accessible for ecosystem manipulation.

Handley, KM [University of California, Berkeley; Verberkmoes, Nathan C [ORNL; Steefel, Carl I [Lawrence Berkeley National Laboratory (LBNL); Sharon, I [University of California, Berkeley; Williams, Ken [Lawrence Berkeley National Laboratory (LBNL); Miller, CS [University of California, Berkeley; Frischkorn, Kyle C [University of California, Berkeley; Chourey, Karuna [ORNL; Thomas, Brian [University of California, Berkeley; Shah, Manesh B [ORNL; Long, Phil [Pacific Northwest National Laboratory (PNNL); Hettich, Robert {Bob} L [ORNL; Banfield, Jillian F. [University of California, Berkeley

2013-01-01

174

Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.  

PubMed Central

To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures and lower cardiac outputs. The oxidation of acetoacetate increased the tissue content of 2-oxoglutarate and glutamate and decreased the content of succinyl-CoA suggesting inhibition of citric acid cycle flux through 2-oxoglutarate dehydrogenase. Whereas hearts perfused with either acetoacetate or glucose were similar with respect to their function for the first 20 min, changes in tissue metabolites were already observed within 5 min of perfusion at near-physiological workloads. The addition of lactate or propionate, but not acetate, to hearts oxidizing acetoacetate improved contractile performance, although inhibition of 2-oxoglutarate dehydrogenase was probably not diminished. If lactate or propionate were added, malate and citrate accumulated indicating utilization of anaplerotic pathways for the citric acid cycle. We conclude that a decreased rate of flux through 2-oxoglutarate dehydrogenase in hearts oxidizing acetoacetate precedes, and may be responsible for, contractile failure and is not the result of decreased cardiac work. Further, anaplerosis play an important role in the maintenance of contractile function in hearts utilizing acetoacetate. Images

Russell, R R; Taegtmeyer, H

1991-01-01

175

Identification of functionally relevant populations in enhanced biological phosphorus removal processes based on intracellular polymers profiles and insights into the metabolic diversity and heterogeneity.  

PubMed

This study proposed and demonstrated the application of a new Raman microscopy-based method for metabolic state-based identification and quantification of functionally relevant populations, namely polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs), in enhanced biological phosphorus removal (EBPR) system via simultaneous detection of multiple intracellular polymers including polyphosphate (polyP), glycogen, and polyhydroxybutyrate (PHB). The unique Raman spectrum of different combinations of intracellular polymers within a cell at a given stage of the EBPR cycle allowed for its identification as PAO, GAO, or neither. The abundance of total PAOs and GAOs determined by Raman method were consistent with those obtained with polyP staining and fluorescence in situ hybridization (FISH). Different combinations and quantities of intracellular polymer inclusions observed in single cells revealed the distribution of different sub-PAOs groups among the total PAO populations, which exhibit phenotypic and metabolic heterogeneity and diversity. These results also provided evidence for the hypothesis that different PAOs may employ different extents of combination of glycolysis and TCA cycle pathways for anaerobic reducing power and energy generation and it is possible that some PAOs may rely on TCA cycle solely without glycolysis. Sum of cellular level quantification of the internal polymers associated with different population groups showed differentiated and distributed trends of glycogen and PHB level between PAOs and GAOs, which could not be elucidated before with conventional bulk measurements of EBPR mixed cultures. PMID:22471394

Majed, Nehreen; Chernenko, Tatyana; Diem, Max; Gu, April Z

2012-05-01

176

Functional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis.  

PubMed

Cell cycle-related kinase (CCRK) is a newly identified protein kinase homologous to Cdk7. We have previously shown that CCRK is a candidate oncogene in human glioblastoma. However, whether CCRK is a bona fide oncogene remains to be tested. The aim of this study was to investigate the role of CCRK in human colorectal cancer carcinogenesis. By Western blotting, we analysed the expression profile of CCRK protein in 10 colorectal cancer tissue samples and their adjacent normal colon tissues and in seven colorectal cancer cell lines. CCRK protein expression was also investigated by immunohistochemistry in a colorectal tissue microarray, which contained 120 cases of primary colorectal cancer and adjacent normal colorectal mucosa. The effects of CCRK knock-down on cell cycle profile and proliferation of colorectal cancer cells were examined by transfecting LoVo and DLD1 human colorectal cancer cell lines by either short-hairpin RNA (shCCRK) or small interfering RNA targeting CCRK (siCCRK). We found that CCRK protein levels were elevated by more than 1.5-fold in 70% of colorectal cancer patient samples examined and CCRK was detectable in all seven colorectal cancer cell lines tested. Colorectal tissue microarray indicated that overexpression of CCRK was detected in 62/109 (56.9%) of informative colorectal cancer cases and was significantly associated with the tumour pT and pN status (p<0.05). Suppression of CCRK by siCCRK led to G1 phase cell cycle arrest and reduced cell growth. Consistently, stable clones of LoVo and DLD1 cells expressing shCCRK exhibited decreased cell proliferation rates. Furthermore, we showed that CCRK is required for the phosphorylation of Cdk2 (on Thr-160) and Rb (on Ser-795) and the expression of cyclin E. These results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. PMID:20466538

An, Xiaomeng; Ng, Samuel S; Xie, Dan; Zeng, Yi-Xin; Sze, Johnny; Wang, Jide; Chen, Yang Chao; Chow, Billy K C; Lu, Gang; Poon, Wai Sang; Kung, Hsiang-Fu; Wong, Benjamin C Y; Lin, Marie Chia-Mi

2010-06-01

177

EFFECTS OF LAND USE CHANGES ON THE FUNCTIONING OF SOILS AND WATERSHEDS OF CENTRAL BRAZIL SAVANNAS: PHASE 2, IMPACTS ON NUTRIENT AND CARBON CYCLES AND TRACE GAS EXCHANGE  

EPA Science Inventory

This research is funded through an interagency agreement with NASA. The research in this project is contributing to assessments of the effects of land use in central Brazil on: 1) the stocks and cycling rates of carbon and nutrient cycling; 2) the function and structure of soil ...

178

The role of surface chemical analysis in a study to select replacement processes for TCA vapor degreasing  

NASA Technical Reports Server (NTRS)

The role of surface-sensitive chemical analysis (ESCA, AES, and SIMS) in a study to select a process to replace 1, 1, 1-trichloroethane (TCA) vapor degreasing as a steel and aluminum bonding surface preparation method is described. The effort was primarily concerned with spray-in-air cleaning processes involving aqueous alkaline and semi-aqueous cleaners and a contamination sensitive epoxy-to-metal bondline. While all five cleaners tested produced bonding strength results equal to or better than those produced by vapor degreasing, the aqueous alkaline cleaners yielded results which were superior to those produced by the semi-aqueous cleaners. The main reason for the enhanced performance appears to be a silicate layer left behind by the aqueous alkaline cleaners. The silicate layer increases the polarity of the surface and enhances epoxy-to-metal bonding. On the other hand, one of the semi-aqueous cleaners left a nonpolar carbonaceous residue which appeared to have a negative effect on epoxy-to-metal bonding. Differences in cleaning efficiency between cleaners/processes were also identified. These differences in surface chemistry, which were sufficient to affect bonding, were not detected by conventional chemical analysis techniques.

Lesley, Michael W.; Davis, Lawrence E.; Moulder, John F.; Carlson, Brad A.

1995-01-01

179

c-Myb regulates cell cycle-dependent expression of Erbin: an implication for a novel function of Erbin.  

PubMed

In the present study, we demonstrated the cell cycle periodicity of Erbin expression with the maximal expression of Erbin in G2/M phase. A significant increase in Erbin promoter activity was observed in G2/M phase-synchronized cells. Sequence analysis revealed a c-Myb site in the core promoter region of Erbin. Mutagenesis of c-Myb consensus sequences abrogated the increased Erbin promoter activity in G2/M phase. ChIP and oligonucleotide pull-down assays validated that the recruitment of c-Myb to the consensus sequences was specific. The interaction of c-Myb with c-Myb site in the Erbin promoter was significantly enhanced in G2/M phase. Ectopic overexpression of c-Myb led to the up-regulation of Erbin promoter activity and c-Myb silencing by small interfering RNA significantly decreased Erbin protein level. Transfection of c-Myb rescued Erbin expression that was impaired by c-Myb knockdown. It proves that c-Myb and the c-Myb response element mediate the cell cycle-dependent expression of Erbin. Inactivation of Erbin causes an acceleration of the G1/S transition, the formation of multipolar spindles and abnormal chromosome congression. These results unravel a critical role of c-Myb in promoting Erbin transcription in G2/M phase and also predict an unappreciated function of Erbin in cell cycle progression. PMID:22880131

Liu, Dan; Shi, Ming; Zhang, Hao; Qian, Lu; Yu, Ming; Hu, Meiru; Zhang, Ruihong; Wang, Tianyou; Han, Caili; Duan, Huijun; Guo, Ning

2012-01-01

180

c-Myb Regulates Cell Cycle-Dependent Expression of Erbin: An Implication for a Novel Function of Erbin  

PubMed Central

In the present study, we demonstrated the cell cycle periodicity of Erbin expression with the maximal expression of Erbin in G2/M phase. A significant increase in Erbin promoter activity was observed in G2/M phase-synchronized cells. Sequence analysis revealed a c-Myb site in the core promoter region of Erbin. Mutagenesis of c-Myb consensus sequences abrogated the increased Erbin promoter activity in G2/M phase. ChIP and oligonucleotide pull-down assays validated that the recruitment of c-Myb to the consensus sequences was specific. The interaction of c-Myb with c-Myb site in the Erbin promoter was significantly enhanced in G2/M phase. Ectopic overexpression of c-Myb led to the up-regulation of Erbin promoter activity and c-Myb silencing by small interfering RNA significantly decreased Erbin protein level. Transfection of c-Myb rescued Erbin expression that was impaired by c-Myb knockdown. It proves that c-Myb and the c-Myb response element mediate the cell cycle-dependent expression of Erbin. Inactivation of Erbin causes an acceleration of the G1/S transition, the formation of multipolar spindles and abnormal chromosome congression. These results unravel a critical role of c-Myb in promoting Erbin transcription in G2/M phase and also predict an unappreciated function of Erbin in cell cycle progression.

Zhang, Hao; Qian, Lu; Yu, Ming; Hu, Meiru; Zhang, Ruihong; Wang, Tianyou; Han, Caili; Duan, Huijun; Guo, Ning

2012-01-01

181

Expression and localization of nodal in bovine oviduct and uterus during different functional stages of oestrus cycle and pregnancy.  

PubMed

Members of TGF-? superfamily play a major role in the endometrial changes involved in the establishment and maintenance of pregnancy. Their deregulated expression and action could lead to absolute or partial failure of embryo implantation. Nonetheless, the precise function and mechanism of many of these cytokines remain unclear. Nodal, a transforming growth factor beta (TGF-?) superfamily member, was characterized in the human and rodent uterus and implicated in the tissue remodeling events during menstruation and embryo implantation. In order to study its possible role in the cattle reproductive process, we have analyzed Nodal expression pattern and localization in the oviduct and uterine horn during the oestrus cycle and early pregnancy (day 20). Nodal was detected both in oviduct and uterus during either the oestrus cycle or pregnancy; however, it shows a differential expression profile in the uterine horn at dioestrus and pregnancy, decreasing 1.5 and 1.4 folds in comparison with oestrus. Nodal immunostaining intensity was observed in stromal and in epithelial cells of the surface and the glandular epithelium. The staining pattern correlates with the RT-qPCR expression profile. This work is the first to evidence the presence of Nodal in the bovine reproductive tract; our data suggest that Nodal is a novel cytokine that would be involved in the remodelling occurring in the endometrium of cattle during the oestrus cycle and in the embryo implantation. The identification of new molecules that participate in endometrium cycling and/or pregnancy may be useful for predicting the ability of the uterine tissue to establish and maintain pregnancy or for detecting the infertility processes. These results highlight Nodal as a possible novel marker of the fertility process, nevertheless further studies should be done to determine its role in the reproductive system. PMID:23052837

Argañaraz, Martin Eduardo; Apichela, Silvana Andrea; Kenngott, Rebecca; Vermeheren, Margarethe; Rodler, Daniela; Palma, Gustavo Adolfo; Miceli, Dora Cristina; Sinowatz, Fred

2013-01-01

182

Rates of insulin secretion in INS-1 cells are enhanced by coupling to anaplerosis and Kreb's cycle flux independent of ATP synthesis  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We studied media effects on mechanisms of insulin secretion of INS-1 cells. Black-Right-Pointing-Pointer Insulin secretion was higher in DMEM than KRB despite identical ATP synthesis rates. Black-Right-Pointing-Pointer Insulin secretion rates correlated with rates of anaplerosis and TCA cycle. Black-Right-Pointing-Pointer Mitochondria metabolism and substrate cycles augment secretion signal of ATP. -- Abstract: Mechanistic models of glucose stimulated insulin secretion (GSIS) established in minimal media in vitro, may not accurately describe the complexity of coupling metabolism with insulin secretion that occurs in vivo. As a first approximation, we have evaluated metabolic pathways in a typical growth media, DMEM as a surrogate in vivo medium, for comparison to metabolic fluxes observed under the typical experimental conditions using the simple salt-buffer of KRB. Changes in metabolism in response to glucose and amino acids and coupling to insulin secretion were measured in INS-1 832/13 cells. Media effects on mitochondrial function and the coupling efficiency of oxidative phosphorylation were determined by fluorometrically measured oxygen consumption rates (OCRs) combined with {sup 31}P NMR measured rates of ATP synthesis. Substrate preferences and pathways into the TCA cycle, and the synthesis of mitochondrial 2nd messengers by anaplerosis were determined by {sup 13}C NMR isotopomer analysis of the fate of [U-{sup 13}C] glucose metabolism. Despite similar incremental increases in insulin secretion, the changes of OCR in response to increasing glucose from 2.5 to 15 mM were blunted in DMEM relative to KRB. Basal and stimulated rates of insulin secretion rates were consistently higher in DMEM, while ATP synthesis rates were identical in both DMEM and KRB, suggesting greater mitochondrial uncoupling in DMEM. The relative rates of anaplerosis, and hence synthesis and export of 2nd messengers from the mitochondria were found to be similar in DMEM to those in KRB. And, the correlation of total PC flux with insulin secretion rates in DMEM was found to be congruous with the correlation in KRB. Together, these results suggest that signaling mechanisms associated with both TCA cycle flux and with anaplerotic flux, but not ATP production, may be responsible for the enhanced rates of insulin secretion in more complex, and physiologically-relevant media.

Cline, Gary W., E-mail: gary.cline@yale.edu [The Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 (United States); Department of Surgery, University of Minnesota-Twin Cities, Minneapolis, MN 55455 (United States); Pongratz, Rebecca L.; Zhao, Xiaojian [The Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 (United States)] [The Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 (United States); Papas, Klearchos K. [Department of Surgery, University of Minnesota-Twin Cities, Minneapolis, MN 55455 (United States)] [Department of Surgery, University of Minnesota-Twin Cities, Minneapolis, MN 55455 (United States)

2011-11-11

183

Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates.  

PubMed Central

Indy is a gene in Drosophila melanogaster which, when made dysfunctional, leads to an extension of the average adult life span of the organism. The present study was undertaken to clone the Indy gene-product and to establish its functional identity. We isolated a full-length Indy cDNA from a D. melanogaster cDNA library. The cDNA codes for a protein of 572 amino acids [( Drosophila Indy (drIndy)]. In its amino acid sequence, drIndy exhibits comparable similarity to the two known Na(+)-coupled dicarboxylate transporters in mammals; namely, NaDC1 (35% identity) and NaDC3 (34% identity). We elucidated the functional characteristics of drIndy in two different heterologous expression systems by using mammalian cells and Xenopus laevis oocytes. These studies show that drIndy is a cation-independent electroneutral transporter for a variety of tricarboxylic acid-cycle intermediates, with preference for citrate compared with succinate. These characteristics of drIndy differ markedly from those of NaDC1 and NaDC3, indicating that neither of these latter transporters is the mammalian functional counterpart of drIndy. Since drIndy is a transporter for tricarboxylic acid-cycle intermediates, dysfunction of the Indy gene may lead to decreased production of metabolic energy in cells, analogous to caloric restriction. This might provide the molecular basis for the observation that disruption of the Indy gene function in Drosophila leads to extension of the average adult life span of the organism.

Inoue, Katsuhisa; Fei, You-Jun; Huang, Wei; Zhuang, Lina; Chen, Zhong; Ganapathy, Vadivel

2002-01-01

184

Old and New Stories: Revelations from Functional Analysis of the Bovine Mammary Transcriptome during the Lactation Cycle  

PubMed Central

The cow mammary transcriptome was explored at ?30, ?15, 1, 15, 30, 60, 120, 240, and 300 d relative to parturition. A total of 6,382 differentially expressed genes (DEG) at a false discovery rate ?0.001 were found throughout lactation. The greatest number of DEG (>3,500 DEG) was observed at 60 and 120 d vs. ?30 d with the largest change between consecutive time points observed at ?15 vs. 1 d and 120 vs. 240 d. Functional analysis of microarray data was performed using the Dynamic Impact Approach (DIA). The DIA analysis of KEGG pathways uncovered as the most impacted and induced ‘Galactose metabolism’, ‘Glycosylphosphatidylinositol (GPI)-anchor biosynthesis’, and ‘PPAR signaling’; whereas, ‘Antigen processing and presentation’ was among the most inhibited. The integrated interpretation of the results suggested an overall increase in metabolism during lactation, particularly synthesis of carbohydrates and lipid. A marked degree of utilization of amino acids as energy source, an increase of protein export, and a decrease of the protein synthesis machinery as well cell cycle also were suggested by the DIA analysis. The DIA analysis of Gene Ontology and other databases uncovered an induction of Golgi apparatus and angiogenesis, and the inhibition of both immune cell activity/migration and chromosome modifications during lactation. All of the highly-impacted and activated functions during lactation were evidently activated at the onset of lactation and inhibited when milk production declined. The overall analysis indicated that the bovine mammary gland relies heavily on a coordinated transcriptional regulation to begin and end lactation. The functional analysis using DIA underscored the importance of genes associated with lactose synthesis, lipid metabolism, protein synthesis, Golgi, transport, cell cycle/death, epigenetic regulation, angiogenesis, and immune function during lactation.

Bionaz, Massimo; Periasamy, Kathiravan; Rodriguez-Zas, Sandra L.; Everts, Robin E.; Lewin, Harris A.; Hurley, Walter L.; Loor, Juan J.

2012-01-01

185

An Assessment of the Efficacy and Safety of CROSS Technique with 100% TCA in the Management of Ice Pick Acne Scars  

PubMed Central

Background: Chemical reconstruction of skin scars (CROSS) is a technique using high concentrations of trichloroacetic acid (TCA) focally on atrophic acne scars to induce inflammation followed by collagenisation. This can lead to reduction in the appearance of scars and cosmetic improvement. Aims: The aim of this pilot study is to investigate the safety of the CROSS technique, using 100% TCA, for atrophic ice pick acne scars. Settings and Design: Open prospective study. Material and Methods: Twelve patients with predominant atrophic ice pick post acne scars were treated with the CROSS technique, using 100% TCA, applied with a wooden toothpick, at two weekly intervals for four sittings. Efficacy was assessed on the basis of the physician’s clinical assessment, photographic evaluation at each sitting and patient’s feedback after the fourth treatment, and at the three-month and six-month follow-up period, after the last treatment. Results: More than 70% improvement was seen in eight out of ten patients evaluated and good results (50 – 70% improvement) were observed in the remaining two patients. No significant side effects were noted. Transient hypopigmentation and hyperpigmentation was observed in one patient each. Physician’s findings were in conformity with the patient’s assessment. Three months after the last treatment, one patient noted a decrease in improvement with no further improvement even at the six-month follow-up period. Conclusion: The CROSS technique with 100% TCA is a safe, efficacious, cost-effective and minimally invasive technique for the management of ice pick acne scars that are otherwise generally difficult to treat. In few patients the improvement may not be sustained, probably due to inadequate or delayed collagenisation.

Bhardwaj, Deepali; Khunger, Niti

2010-01-01

186

Functional safety and system security in automation systems - a life cycle model  

Microsoft Academic Search

Industrial and building automation systems are more and more important in industry and buildings. New services and novel fields of application call for dependable systems. Two very important properties of such a system are functional safety and system security. In the opposite of today's development where safety and security are treated separately, investigating security together with safety leads to a

Thomas Novak; Albert Treytl

2008-01-01

187

Cycling, stressed-out and nervous: cellular functions of c-Abl  

Microsoft Academic Search

c-Abl, the product of the cellular homologue of the transforming gene of Abelson murine leukaemia virus, has been a protein in search of a purpose for over two decades. Because c-Abl is implicated in the pathogenesis of several human leukaemias, understanding the functions of Abl is an important goal. Recently, biochemical and genetic approaches have converged to shed new light

Richard A. Van Etten

1999-01-01

188

Some evidence on determinants of fuel economy as a function of driving cycle and test type  

NASA Astrophysics Data System (ADS)

Statistical methods are used with 107 vehicles whose fuel economy was presented and reported for five test types in a single publication by Consumers Union (CU) for 1986-1988 vehicles. Standard loglinear statistical formulations (i.e., multiplicative models of interactions) are used with data from this and supplementary sources to develop coefficients estimating the percent fuel economy gain per percent change in engine/vehicle design characteristic. The coefficients are developed for the five different test conditions evaluated by CU and are compared with each other on the basis of attributes of the tests. The insights of engineering models are used to develop expectations regarding the shift in size of coefficients as driving cycles change. In both the engineering models and the statistical model, the effect of weight is estimated to be higher in urban driving than in highway driving. For two test categories - field tests and dynamometer tests - the benefits of weight reduction are statistically estimated to be greatest in urban driving conditions. The effect on idle fuel flow rate of designing vehicles to hold performance roughly constant by maintaining power per kilogram and/or displacement per kilogram is examined, and its implication for the size of the weight effect is simply approximated from Sovran's 1983 engineering model results. The fuel-economy-decreasing effect of the desire for performance is estimated to be somewhat larger in the statistical analysis than in the NAS study, when engine technology is held constant.

Santini, D. J.; Anderson, J.

189

13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS)  

Microsoft Academic Search

Cellular metabolism of glucose is required for stimulation of insulin secretion from pancreatic cells, but the precise metabolic coupling factors involved in this process are not known. In an effort to better understand mechanisms of fuel-mediated insulin secretion, we have adapted 13C NMR and isotopomer methods to measure influx of metabolic fuels into the tricarboxylic acid (TCA) cycle in insulinoma

Danhong Lu; Hindrik Mulder; Piyu Zhao; Shawn C. Burgess; Mette V. Jensen; Svetlana Kamzolova; Christopher B. Newgard; A. Dean Sherry

2002-01-01

190

Highlighting the tricarboxylic acid cycle: liquid and gas chromatography-mass spectrometry analyses of (13)C-labeled organic acids.  

PubMed

The tricarboxylic acid (TCA) cycle is involved in the complete oxidation of organic acids to carbon dioxide in aerobic cells. It not only uses the acetyl-CoA derived from glycolysis but also uses breakdown products of proteins, fatty acids, and nucleic acids. Therefore, the TCA cycle involves numerous carbon fluxes through central metabolism to produce reductant power and transfer the generated electrons to the aerobic electron transport system where energy is formed by oxidative phosphorylation. Although the TCA cycle plays a crucial role in aerobic organisms and tissues, the lack of direct isotopic labeling information in its intermediates (organic acids) makes the quantification of its metabolic fluxes rather approximate. This is the major technical gap that this study intended to fill. In this work, we established and validated liquid and gas chromatography-mass spectrometry methods to determine (13)C labeling in organic acids involved in the TCA cycle using scheduled multiple reaction monitoring and single ion monitoring modes, respectively. Labeled samples were generated using maize embryos cultured with [(13)C]glucose or [(13)C]glutamine. Once steady-state labeling was reached, (13)C-labeled organic acids were extracted and purified. When applying our mass spectrometric methods to those extracts, mass isotopomer abundances of seven major organic acids were successfully determined. PMID:23399391

Koubaa, Mohamed; Cocuron, Jean-Christophe; Thomasset, Brigitte; Alonso, Ana Paula

2013-05-15

191

The RNA polymerase trigger loop functions in all three phases of the transcription cycle.  

PubMed

The trigger loop (TL) forms a conserved element in the RNA polymerase active centre that functions in the elongation phase of transcription. Here, we show that the TL also functions in transcription initiation and termination. Using recombinant variants of RNA polymerase from Pyrococcus furiosus and a reconstituted transcription system, we demonstrate that the TL is essential for initial RNA synthesis until a complete DNA-RNA hybrid is formed. The archaeal TL is further important for transcription fidelity during nucleotide incorporation, but not for RNA cleavage during proofreading. A conserved glutamine residue in the TL binds the 2'-OH group of the nucleoside triphosphate (NTP) to discriminate NTPs from dNTPs. The TL also prevents aberrant transcription termination at non-terminator sites. PMID:23737452

Fouqueau, Thomas; Zeller, Mirijam E; Cheung, Alan C; Cramer, Patrick; Thomm, Michael

2013-08-01

192

An N-Myristoylated Globin with a Redox-Sensing Function That Regulates the Defecation Cycle in Caenorhabditis elegans  

PubMed Central

Globins occur in all kingdoms of life where they fulfill a wide variety of functions. In the past they used to be primarily characterized as oxygen transport/storage proteins, but since the discovery of new members of the globin family like neuroglobin and cytoglobin, more diverse and complex functions have been assigned to this heterogeneous family. Here we propose a function for a membrane-bound globin of C. elegans, GLB-26. This globin was predicted to be myristoylated at its N-terminus, a post-translational modification only recently described in the globin family. In vivo, this globin is found in the membrane of the head mesodermal cell and in the tail stomato-intestinal and anal depressor muscle cells. Since GLB-26 is almost directly oxidized when exposed to oxygen, we postulate a possible function as electron transfer protein. Phenotypical studies show that GLB-26 takes part in regulating the length of the defecation cycle in C. elegans under oxidative stress conditions.

Tilleman, Lesley; De Henau, Sasha; Pauwels, Martje; Nagy, Nora; Pintelon, Isabel; Braeckman, Bart P.; De Wael, Karolien; Van Doorslaer, Sabine; Adriaensen, Dirk; Timmermans, Jean-Pierre; Moens, Luc; Dewilde, Sylvia

2012-01-01

193

Influence of functional unit on the life cycle assessment of traction batteries  

Microsoft Academic Search

Goal, Scope and Background  This paper describes the influence of the choice of the functional unit on the results of an environmental assessment of different\\u000a battery technologies for electric and hybrid vehicles. Battery, hybrid and fuel cell electric vehicles are considered as being\\u000a environmentally friendly. However, the batteries they use are sometimes said to be environmentally unfriendly. At the current\\u000a state

Julien Matheys; Wout Van Autenboer; Jean-Marc Timmermans; Joeri Van Mierlo; Peter Van den Bossche; Gaston Maggetto

2007-01-01

194

The role of the tricarboxylic acid cycle in citric acid accumulation by Aspergillus niger  

Microsoft Academic Search

Determinations of the momentary levels of various intermediates related to the activity of the tricarboxylic acid cycle have been made during citric acid production in high-accumulating (manganese deficient) and lowaccumulating (manganese supplemented) mycelia of Aspergillus niger. During the growth period the levels of almost all TCA cycle acids, with the exception of 2-oxo-acids, were unusually high; during the induction phase

C. P. Kubicek; M. Röhr

1978-01-01

195

Soil warming alters nitrogen cycling in a New England forest: implications for ecosystem function and structure.  

PubMed

Global climate change is expected to affect terrestrial ecosystems in a variety of ways. Some of the more well-studied effects include the biogeochemical feedbacks to the climate system that can either increase or decrease the atmospheric load of greenhouse gases such as carbon dioxide and nitrous oxide. Less well-studied are the effects of climate change on the linkages between soil and plant processes. Here, we report the effects of soil warming on these linkages observed in a large field manipulation of a deciduous forest in southern New England, USA, where soil was continuously warmed 5°C above ambient for 7 years. Over this period, we have observed significant changes to the nitrogen cycle that have the potential to affect tree species composition in the long term. Since the start of the experiment, we have documented a 45% average annual increase in net nitrogen mineralization and a three-fold increase in nitrification such that in years 5 through 7, 25% of the nitrogen mineralized is then nitrified. The warming-induced increase of available nitrogen resulted in increases in the foliar nitrogen content and the relative growth rate of trees in the warmed area. Acer rubrum (red maple) trees have responded the most after 7 years of warming, with the greatest increases in both foliar nitrogen content and relative growth rates. Our study suggests that considering species-specific responses to increases in nitrogen availability and changes in nitrogen form is important in predicting future forest composition and feedbacks to the climate system. PMID:21983640

Butler, S M; Melillo, J M; Johnson, J E; Mohan, J; Steudler, P A; Lux, H; Burrows, E; Smith, R M; Vario, C L; Scott, L; Hill, T D; Aponte, N; Bowles, F

2012-03-01

196

Effect of yoga on autonomic functions and psychological status during both phases of menstrual cycle in young healthy females.  

PubMed

Context: Premenstrual stress affects 75% of women of childbearing age and yoga has been found to be beneficial in many psycho-somatic disorders. Aims: To investigate the effect of integrated yoga on autonomic parameters and psychological well-being during both pre and post phases of menstrual cycle in healthy young female subjects. Settings and Design: Present study is a randomized control trial and was conducted in the Department of Physiology, Lady Hardinge Medical College, New Delhi, India. Material and Methods: Fifty apparently healthy females in the age group of 18-20 years were randomized into two groups: Group I (n=25) consisted of subjects who practiced yoga 35-40 minutes per day, six times per week for the duration of three menstrual cycles. Training was given by qualified yoga instructor. Group II (n=25) subjects acted as controls. Following parameters were recorded at the beginning and after completion of three menstrual cycles in all the subjects: Height, weight (BW), Resting Heart Rate (HR), Resting Systolic (SBP) and Diastolic Blood Pressure (DBP), parasympathetic reactivity tests including Expiration-Inspiration Ratio (E: I ratio) and 30:15 ratio, sympathetic reactivity tests including BP changes due to Isometric Hand Grip (IHG) exercise, and Cold Pressor Test (CPT). Assessment of psychological status was done by administering DIPAS (Defense Institute of Physiology and Allied Sciences) inventories of Anger self report scale, Trait Anxiety, Sense of well-being and Depression scale. Statistical Analysis: Intra-group comparison of physiological parameters was done by using paired 't' test, whereas intra-group comparison of non-parameteric data such as scores of anxiety, depression, anger and sense of well-being was done by Wilcoxon signed-rank test. Inter-group comparison of parameters was done by Students 't' test for parametric tests and Mann-Whitney 'U' test for non-parameteric tests. Results: There was significantly higher BW, resting SBP, DBP, sympathetic activity and blunting of parasympathetic reactivity and also, significantly higher scores of anger, depression, anxiety and decreased score of well-being in premenstrual phase as compared to postmenstrual phase in both the groups in initial cycle. There was significantly higher percentage decrease in BW, HR, SBP & DBP in yoga group as compared to control group in both the phases from initial to second and onwards between second and third menstrual cycle. Also, decrease in anger, depression and anxiety and increase in well-being score was significant in yoga group as compared to control group from initial to second and third cycle in premenstrual phase while the change was significant only in depression score in postmenstrual phase. Conclusion: Our study shows that there was significant alteration of autonomic functions and psychological status in premenstrual phase when compared with postmenstrual phase in young healthy females. Also, regular practice of yoga has beneficial effects on both phases of menstrual cycle by bringing parasympathodominance and psychological well-being probably by balancing neuro-endocrinal axis. PMID:24298457

Kanojia, Sarita; Sharma, Vivek Kumar; Gandhi, Asha; Kapoor, Raj; Kukreja, Ajay; Subramanian, Senthil Kumar

2013-10-01

197

The role of biodiversity for the carbon cycle: Implementation of functional diversity in a dynamic vegetation model  

NASA Astrophysics Data System (ADS)

Most dynamic global vegetation models (DGVMs) condense natural plant diversity to plant functional types (PFTs). A single PFT usually represents a whole biome, e.g. the PFT "tropical broadleaved evergreen tree" and its constant set of functional trait parameters covers entire regions in the model. This approach minimizes functional diversity and neglects the effects of functional diversity on the modeled vegetation and carbon dynamics. Our work aims to overcome this limitation and extend functional diversity in the vegetation model LPJmL to explore the role of biodiversity in climate change mitigation. Our approach improves the representation of biodiversity in the model by incorporating the natural ranges and eco-physiological interrelations of relevant plant traits. Empirical data on plant traits is provided by the TRY data base (www.try-db.org) and the ROBIN project (www.robinproject.info). A first sensitivity analysis revealed that simulated carbon stocks are very stable under a large range of trait combinations. However, several model output variables appeared highly sensitive to small changes of plant trait parameters and thus the introduction of trait ranges requires several improvements of the PFT concept of LPJmL. One possible way of improvement is to implement missing plant-trait tradeoffs, which will be used to simulate the growth of individual plants with flexible parameter combinations at the landscape scale. Our improved model will enable for the simulation of local competition and complementarity of individual plants which, according to their trait values and ranges, can then be categorized into a much broader variety of PFTs. This modeling approach will allow for investigating the role of bio- and functional diversity in the global carbon cycle as well as in regional vegetation dynamics.

Sakschewski, Boris; Boit, Alice; von Bloh, Werner; Rammig, Anja; Thonicke, Kirsten

2013-04-01

198

Toxicity of functionalized single-walled carbon nanotubes on soil microbial communities: implications for nutrient cycling in soil.  

PubMed

Culture-dependent and -independent methods were employed to determine the impact of carboxyl-functionalized single-walled carbon nanotubes (SWNTs) on fungal and bacterial soil microbial communities. Soil samples were exposed to 0 (control), 250, and 500 ?g of SWNTs per gram of soil. Aliquots of soil were sampled for up to 14 days for culture-dependent analyses, namely, plate count agar and bacterial community level physiological profiles, and culture-independent analyses, namely, quantitative real-time polymerase chain reaction (qPCR), mutliplex-terminal restriction fragment length polymorphism (M-TRFLP), and clone libraries. Results from culture-independent and -dependent methods show that the bacterial soil community is transiently affected by the presence of SWNTs. The major impact of SWNTs on bacterial community was observed after 3 days of exposure, but the bacterial community completely recovered after 14 days. However, no recovery of the fungal community was observed for the duration of the experiment. Physiological and DNA microbial community analyses suggest that fungi and bacteria involved in carbon and phosphorus biogeochemical cycles can be adversely affected by the presence of SWNTs. This study suggests that high concentrations of SWNTs can have widely varying effects on microbial communities and biogeochemical cycling of nutrients in soils. PMID:23205469

Rodrigues, Debora F; Jaisi, Deb P; Elimelech, Menachem

2013-01-01

199

Sexual reproduction in the Candida clade: cryptic cycles, diverse mechanisms, and alternative functions  

PubMed Central

To have sex, or not to have sex, is a question posed by many microorganisms. In favor of a sexual lifestyle is the associated rearrangement of genetic material that confers potential fitness advantages, including resistance to antimicrobial agents. The asexual lifestyle also has benefits, as it preserves complex combinations of genes that may be optimal for pathogenesis. For this reason, it was thought that several pathogenic fungi favored strictly asexual modes of reproduction. Recent approaches using genome sequencing, population analysis, and experimental techniques have now revised this simplistic picture. It is now apparent that many pathogenic fungi have retained the ability to undergo sexual reproduction, although reproduction is primarily clonal in origin. In this review, we highlight the current understanding of sexual programs in the Candida clade of species. We also examine evidence that sexual-related processes can be used for functions in addition to mating and recombination in these organisms.

Alby, Kevin; Bennett, Richard J.

2010-01-01

200

In situ Expression of Functional Genes Reveals Nitrogen Cycling at High Temperatures in Terrestrial Hydrothermal Systems  

NASA Astrophysics Data System (ADS)

An essential element for life, nitrogen occurs in all living organisms and is critical for the synthesis of amino acids, proteins, nucleic acids, and other forms of biomass. Thus, nitrogen cycling likely plays a vital role in microbial metabolic processes as well as nutrient availability. For microorganisms in "extreme" environments, this means developing adaptations that allow them to survive in harsh conditions and still perform the metabolisms essential to sustain life. Recent studies have screened biofilms and thermal sediments of Yellowstone National Park (YNP) thermal features for the presence of nifH genes, which code for a key enzyme in the nitrogen fixation process [1-4]. Furthermore, analysis of nitrogen isotopes in biofilms across a temperature and chemical gradient revealed that nitrogen fixation likely varies across the chemosynthetic/photosynthetic ecotone [5]. Although research has evaluated and confirmed the presence of nifH genes in various thermophilic microbial communities, the existence of a gene in the DNA of an organism does not verify its use. Instead, other methods, such as culturing, isotope tracer assays, and gene expression studies are required to provide direct evidence of biological nitrogen fixation. Culturing and isotope tracer approaches have successfully revealed high-temperature biological nitrogen fixation in both marine hydrothermal vent microbial communities [6] and in acidic, terrestrial hydrothermal sediment [3]. Transcriptomics-based techniques (using mRNA extracted from samples to confirm in situ expression of targeted genes) have been much more limited in number, and only a few studies have, to date, investigated in situ expression of the nifH gene in thermophilic microbial communities [2, 7]. This study explores the presence and expression of nifH genes in several features of the Lower Geyser Basin (LGB) of YNP. Nucleic acids from chemosynthetic and photosynthetic microbial communities were extracted and then amplified using (reverse-transcription) polymerase chain reaction to identify the presence and expression of nifH genes, and resultant (RT-)PCR product was cloned and sequenced. Results reveal high-temperature in situ expression of nifH in select LGB features [7] which is, to the authors' knowledge, the first direct evidence of nifH transcription in the chemosynthetic zones of terrestrial hydrothermal systems. Results also indicate the presence of novel nifH sequences and allow phylogenetic comparison of nifH genes along geochemical gradients within individual hot spring features and between various thermal features in the LGB. Collectively, these results provide evidence for microbial adaptations that have led to the ability to support basic metabolic processes under "extreme" conditions. [1] Hall et al., 2008. AEM 74: 4910-4922. [2] Steunou et al., 2008. The ISME Journal 2: 364-378. [3] Hamilton et al., 2011. Microb Ecol DOI 10.1007/s00248-011-9824-9. [4] Raymond et al., 2008. EOS Trans AGU. Abstract B14A-03. [5] Havig et al., 2010. J Geophys Res-Biogeo 116: G01005. [6] Mehta & Baross, 2006. Science 314: 1783-1786. [7] Loiacono et al., 2011. Submitted FEMS Microbiol Ecol.

Loiacono, S. T.; Meyer-Dombard, D. R.

2011-12-01

201

The Functional Organization and Control of Plant Respiration  

Microsoft Academic Search

The respiratory pathways of glycolysis, the tricarboxylic acid (TCA) cycle, and mitochondrial electron transport chain (miETC) are central features of carbon metabolism and bioenergetics in aerobic organisms. Respiration is essential for growth, maintenance, and carbon balance of all plant cells. Although the majority of respiratory enzymes are common to all organisms, plant respiration has evolved as a complex metabolic network

William C. Plaxton; Florencio E. Podestá

2006-01-01

202

A Functional Analysis of the Influence of ?3-adrenoceptors on the Rat Micturition Cycle  

PubMed Central

Dysfunctions of the lower urinary tract, such as overactive bladder syndrome and incontinence, are the product of storage failure. Spontaneous regional bladder wall movements [nonmicturition contractions (NMCs)] are proposed to generate afferent activity that signals volume status to the central nervous system. The sympathetic nervous system, via activation of ?-adrenoceptors (?-ARs), causes bladder relaxation and promotes urine storage. We hypothesized that ?-AR regulation of micturition is mediated by suppression of NMCs. We used an unanesthetized, decerebrate, artificially perfused rat preparation that allows simultaneous cystometry with external urethral sphincter and pelvic afferent nerve recordings. Systemic isoprenaline (10 nM to 1 µM) increased intervoid interval and bladder compliance accompanied by a decrease in NMC amplitude, voiding pressure, and voiding threshold. Isoprenaline also reduced arterial pressure and increased heart rate. The ?3-AR agonist mirabegron (10–100 nM) increased intervoid interval and bladder compliance and reduced NMC amplitude, yet preserved active voiding function and had no effect on arterial pressure or heart rate. All of these effects of mirabegron were blocked by the selective ?3-AR antagonist N-[[3-[(2S)-2-hydroxy-3-[[2-[4-[(phenylsulfonyl)amino] phenyl]ethyl]amino]propoxy]phenyl]methyl]-acetamide (L748,337), which alone shortened intervoid interval and decreased bladder compliance—suggesting the presence of a basal ?3-AR–mediated sympathetic tone. Similar effects of mirabegron were seen in an acetic acid–sensitized bladder preparation and in preparations after loss of spinobulbar reflex bladder control. The ?3-AR–mediated increase in intervoid interval correlated with increased bladder compliance but not with the decrease in NMC amplitude. These findings indicate that ?3-adrenoceptors have a selective effect that improves urine storage by increasing compliance without affecting the active components of voiding.

Sadananda, Prajni; Drake, Marcus J.; Paton, Julian F. R.

2013-01-01

203

A functional analysis of the influence of ?3-adrenoceptors on the rat micturition cycle.  

PubMed

Dysfunctions of the lower urinary tract, such as overactive bladder syndrome and incontinence, are the product of storage failure. Spontaneous regional bladder wall movements [nonmicturition contractions (NMCs)] are proposed to generate afferent activity that signals volume status to the central nervous system. The sympathetic nervous system, via activation of ?-adrenoceptors (?-ARs), causes bladder relaxation and promotes urine storage. We hypothesized that ?-AR regulation of micturition is mediated by suppression of NMCs. We used an unanesthetized, decerebrate, artificially perfused rat preparation that allows simultaneous cystometry with external urethral sphincter and pelvic afferent nerve recordings. Systemic isoprenaline (10 nM to 1 µM) increased intervoid interval and bladder compliance accompanied by a decrease in NMC amplitude, voiding pressure, and voiding threshold. Isoprenaline also reduced arterial pressure and increased heart rate. The ?3-AR agonist mirabegron (10-100 nM) increased intervoid interval and bladder compliance and reduced NMC amplitude, yet preserved active voiding function and had no effect on arterial pressure or heart rate. All of these effects of mirabegron were blocked by the selective ?3-AR antagonist N-[[3-[(2S)-2-hydroxy-3-[[2-[4-[(phenylsulfonyl)amino] phenyl]ethyl]amino]propoxy]phenyl]methyl]-acetamide (L748,337), which alone shortened intervoid interval and decreased bladder compliance-suggesting the presence of a basal ?3-AR-mediated sympathetic tone. Similar effects of mirabegron were seen in an acetic acid-sensitized bladder preparation and in preparations after loss of spinobulbar reflex bladder control. The ?3-AR-mediated increase in intervoid interval correlated with increased bladder compliance but not with the decrease in NMC amplitude. These findings indicate that ?3-adrenoceptors have a selective effect that improves urine storage by increasing compliance without affecting the active components of voiding. PMID:24008334

Sadananda, Prajni; Drake, Marcus J; Paton, Julian F R; Pickering, Anthony E

2013-11-01

204

Outcomes of a Home Cycling Program Using Functional Electrical Stimulation or Passive Motion for Children With Spinal Cord Injury: A Case Series  

PubMed Central

Background/Objective: Children with spinal cord injury (SCI) are at risk for musculoskeletal and cardiovascular complications. Stationary cycling using functional electrical stimulation (FES) or passive motion has been suggested to address these complications. The purpose of this case series is to report the outcomes of a 6-month at-home cycling program for 4 children with SCI. Methods: Two children cycled with FES and 2 cycled passively at home for 1 hour, 3 times per week. Outcome Measures: Data collected included bone mineral density of the left femoral neck, distal femur, and proximal tibia; quadriceps and hamstring muscle volume; stimulated quadriceps and hamstring muscle strength; a fasting lipid profile; and heart rate and oxygen consumption during incremental upper extremity ergometry testing. Results: The 2 children cycling with FES and 1 child cycling passively exhibited improved bone mineral density, muscle volume, stimulated quadriceps strength, and lower resting heart rate. For the second child cycling passively, few changes were realized. Overall, the lipid results were inconsistent, with some positive and some negative changes seen. Conclusions: This case series suggests that cycling with or without FES may have positive health benefits and was a practical home exercise option for these children with SCI.

Johnston, Therese E; Smith, Brian T; Oladeji, Oluwabunmi; Betz, Randal R; Lauer, Richard T

2008-01-01

205

Extra-cell cycle regulatory functions of cyclin-dependent kinases (CDK) and CDK inhibitor proteins contribute to brain development and neurological disorders.  

PubMed

In developing brains, neural progenitors exhibit cell cycle-dependent nuclear movement within the ventricular zone [interkinetic nuclear migration (INM)] and actively proliferate to produce daughter progenitors and/or neurons, whereas newly generated neurons exit from the cell cycle and begin pial surface-directed migration and maturation. Dysregulation of the balance between the proliferation and the cell cycle exit in neural progenitors is one of the major causes of microcephaly (small brain). Recent studies indicate that cell cycle machinery influences not only the proliferation but also INM in neural progenitors. Furthermore, several cell cycle-related proteins, including p27(kip1) , p57(kip2) , Cdk5, and Rb, regulate the migration of neurons in the postmitotic state, suggesting that the growth arrest confers dual functions on cell cycle regulators. Consistently, several types of microcephaly occur in conjunction with neuronal migration disorders, such as periventricular heterotopia and lissencephaly. However, cell cycle re-entry by disturbance of growth arrest in mature neurons is thought to trigger neuronal cell death in Alzheimer's disease. In this review, we introduce the cell cycle protein-mediated regulation of two types of nuclear movement, INM and neuronal migration, during cerebral cortical development, and discuss the roles of growth arrest in cortical development and neurological disorders. PMID:23294285

Kawauchi, Takeshi; Shikanai, Mima; Kosodo, Yoichi

2013-03-01

206

Cell cycle function of a rice B2-type cyclin interacting with a B-type cyclin-dependent kinase.  

PubMed

Cyclin-dependent kinases (CDKs) are involved in the control of cell cycle progression. Plant A-type CDKs are functional homologs of yeast Cdc2/Cdc28 and are expressed throughout the cell cycle. In contrast, B-type CDK (CDKB) is a family of mitotic CDKs expressed during the S/M phase, and its precise function remains unknown. Here, we identified two B2-type cyclins, CycB2;1 and CycB2;2, as a specific partner of rice CDKB2;1. The CDKB2;1-CycB2 complexes produced in insect cells showed a significant level of kinase activity in vitro, suggesting that CycB2 binds to and activates CDKB2. We then expressed green fluorescent protein (GFP)-fused CDKB2;1 and CycB2;2 in tobacco BY2 cells to investigate their subcellular localization during mitosis. Surprisingly, the fluorescence signal of CDKB2;1-GFP was tightly associated with chromosome alignment as well as with spindle structure during the metaphase. During the telophase, the signal was localized to the spindle midzone and the separating sister chromosomes, and then to the phragmoplast. On the other hand, the CycB2;2-GFP fluorescence signal was detected in nuclei during the interphase and prophase, moved to the metaphase chromosomes, and then disappeared completely after the cells passed through the metaphase. Co-localization of CDKB2;1-GFP and CycB2;2-GFP on chromosomes aligned at the center of the metaphase cells suggests that the CDKB2-CycB2 complex may function in retaining chromosomes at the metaphase plate. Overexpression of CycB2;2 in rice plants resulted in acceleration of root growth without any increase in cell size, indicating that CycB2;2 promoted cell division probably through association with CDKB2 in the root meristem. PMID:12753582

Lee, Jeongkyung; Das, Avijit; Yamaguchi, Masatoshi; Hashimoto, Junji; Tsutsumi, Nobuhiro; Uchimiya, Hirofumi; Umeda, Masaaki

2003-05-01

207

Data Corrections and Wind-Tunnel Data Comparisons of a 5% TCA Model in the NASA Ames 12-ft Pressure Tunnel  

NASA Technical Reports Server (NTRS)

The objectives of this research are: 1) To determine the effect of geometric variations near the inboard leading-edge flap on high-lift and stability and control performance data; 2) To determine Re effects on TCA (Technology Concept Aircraft) high-lift configuration for optimum high-lift and stability and control performance at takeoff, climbout, approach and landing conditions; and 3) To obtain flow-visualization data on upper surface of wing for CFD validations. This paper is presented in viewgraph form.

Zuniga, Fanny A.

1999-01-01

208

Rates of insulin secretion in INS-1 cells are enhanced by coupling to anaplerosis and Kreb's cycle flux independent of ATP synthesis  

PubMed Central

Mechanistic models of glucose stimulated insulin secretion (GSIS) established in minimal media in vitro, may not accurately describe the complexity of coupling metabolism with insulin secretion that occurs in vivo. As a first approximation, we have evaluated metabolic pathways in a typical growth media, DMEM as a surrogate in vivo medium, for comparison to metabolic fluxes observed under the typical experimental conditions using the simple salt-buffer of KRB. Changes in metabolism in response to glucose and amino acids and coupling to insulin secretion were measured in INS-1 832/13 cells. Media effects on mitochondrial function and the coupling efficiency of oxidative phosphorylation were determined by fluorometrically measured oxygen consumption rates (OCR) combined with 31P-NMR measured rates of ATP synthesis. Substrate preferences and pathways into the TCA cycle, and the synthesis of mitochondrial 2nd messengers by anaplerosis were determined by 13C-NMR isotopomer analysis of the fate of [U-13C]glucose metabolism. Despite similar incremental increases in insulin secretion, the changes of OCR in response to increasing glucose from 2.5 to 15 mM were blunted in DMEM relative to KRB. Basal and stimulated rates of insulin secretion rates were consistently higher in DMEM, while ATP synthesis rates were identical in both DMEM and KRB, suggesting greater mitochondrial uncoupling in DMEM. The relative rates of anaplerosis, and hence synthesis and export of 2nd messengers from the mitochondria were found to be similar in DMEM to those in KRB. And, the correlation of total PC flux with insulin secretion rates in DMEM was found to be congruous with the correlation in KRB. Together, these results suggest that signaling mechanisms associated with both TCA cycle flux and with anaplerotic flux, but not ATP production, may be responsible for the enhanced rates of insulin secretion in more complex, and physiologically-relevant media.

Cline, Gary W.; Pongratz, Rebecca L.; Zhao, Xiaojian; Papas, Klearchos K.

2011-01-01

209

Small RNA-dependent Expression of Secondary Metabolism Is Controlled by Krebs Cycle Function in Pseudomonas fluorescens*  

PubMed Central

Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the rhizosphere of crop plants, elaborates and excretes several secondary metabolites with antibiotic properties. Their synthesis depends on three small RNAs (RsmX, RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two-component system at high cell population densities. To find regulatory links between primary and secondary metabolism in P. fluorescens and in the related species Pseudomonas aeruginosa, we searched for null mutations that affected central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp reporter constructs but without slowing down the growth rate in rich media. Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase isoenzyme) resulted in up-regulation of the three small RNAs and secondary metabolism in the absence of detectable nutrient limitation. These effects required the GacS sensor kinase but not the accessory sensors RetS and LadS. An analysis of intracellular metabolites in P. fluorescens revealed a strong positive correlation between small RNA expression and the pools of 2-oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates (already known to control GacA-dependent virulence factors in P. aeruginosa) exert a critical trigger function in secondary metabolism via the expression of GacA-dependent small RNAs.

Takeuchi, Kasumi; Kiefer, Patrick; Reimmann, Cornelia; Keel, Christoph; Dubuis, Christophe; Rolli, Joelle; Vorholt, Julia A.; Haas, Dieter

2009-01-01

210

Functional features and genomic organization of mouse NaCT, a sodium-coupled transporter for tricarboxylic acid cycle intermediates.  

PubMed

In the present study, we report on the molecular cloning and functional characterization of mouse NaCT (Na+-coupled citrate transporter), the mouse orthologue of Drosophila Indy. Mouse NaCT consists of 572 amino acids and is highly similar to rat and human NaCTs in primary sequence. The mouse nact gene coding for the transporter is approx. 23 kb long and consists of 12 exons. When expressed in mammalian cells, the cloned transporter mediates the Na+-coupled transport of citrate and succinate. Competition experiments reveal that mouse NaCT also recognizes other tricarboxylic acid cycle intermediates such as malate, fumarate and 2-oxo-glutarate as excellent substrates. The Michaelis-Menten constant for the transport process is 38+/-5 mM for citrate and 37+/-6 mM for succinate at pH 7.5. The transport process is electrogenic and exhibits an obligatory requirement for Na+. Na+-activation kinetics indicates that multiple Na+ ions are involved in the activation process. Extracellular pH has a differential effect on the transport function of mouse NaCT depending on whether the transported substrate is citrate or succinate. The Michaelis-Menten constants for these substrates are also influenced markedly by pH. When examined in the Xenopus laevis oocyte expression system with the two-microelectrode voltage-clamp technique, the transport process mediated by mouse NaCT is electrogenic. The charge-to-substrate ratio is 1 for citrate and 2 for succinate. The most probable transport mechanism predicted by these studies involves the transport of citrate as a tervalent anion and succinate as a bivalent anion with a fixed Na+/substrate stoichiometry of 4:1. The present study provides the first unequivocal evidence for the electrogenic nature of mammalian NaCT. PMID:14656221

Inoue, Katsuhisa; Fei, You-Jun; Zhuang, Lina; Gopal, Elangovan; Miyauchi, Seiji; Ganapathy, Vadivel

2004-03-15

211

Color-coded measures of myocardial velocity throughout the cardiac cycle by tissue Doppler imaging to quantify regional left ventricular function  

Microsoft Academic Search

TDI is a new echocardiographic technique that calculates and displays color-coded myocardial velocity on-line. To determine the feasibility of endocardial velocity throughout the cardiac cycle as a means to quantify regional function, 20 normal subjects aged 30 ± 5 years and 12 patients with heart disease aged 62 ± 17 years were studied with a prototype TDI system. TDI M-mode

John Gorcsan; Vijay K. Gulati; William A. Mandarino; William E. Katz

1996-01-01

212

Elementary flux modes analysis of functional domain networks allows a better metabolic pathway interpretation.  

PubMed

Metabolic network analysis is an important step for the functional understanding of biological systems. In these networks, enzymes are made of one or more functional domains often involved in different catalytic activities. Elementary flux mode (EFM) analysis is a method of choice for the topological studies of these enzymatic networks. In this article, we propose to use an EFM approach on networks that encompass available knowledge on structure-function. We introduce a new method that allows to represent the metabolic networks as functional domain networks and provides an application of the algorithm for computing elementary flux modes to analyse them. Any EFM that can be represented using the classical representation can be represented using our functional domain network representation but the fine-grained feature of functional domain networks allows to highlight new connections in EFMs. This methodology is applied to the tricarboxylic acid cycle (TCA cycle) of Bacillus subtilis, and compared to the classical analyses. This new method of analysis of the functional domain network reveals that a specific inhibition on the second domain of the lipoamide dehydrogenase (pdhD) component of pyruvate dehydrogenase complex leads to the loss of all fluxes. Such conclusion was not predictable in the classical approach. PMID:24204596

Pérès, Sabine; Felicori, Liza; Molina, Franck

2013-01-01

213

Elementary Flux Modes Analysis of Functional Domain Networks Allows a Better Metabolic Pathway Interpretation  

PubMed Central

Metabolic network analysis is an important step for the functional understanding of biological systems. In these networks, enzymes are made of one or more functional domains often involved in different catalytic activities. Elementary flux mode (EFM) analysis is a method of choice for the topological studies of these enzymatic networks. In this article, we propose to use an EFM approach on networks that encompass available knowledge on structure-function. We introduce a new method that allows to represent the metabolic networks as functional domain networks and provides an application of the algorithm for computing elementary flux modes to analyse them. Any EFM that can be represented using the classical representation can be represented using our functional domain network representation but the fine-grained feature of functional domain networks allows to highlight new connections in EFMs. This methodology is applied to the tricarboxylic acid cycle (TCA cycle) of Bacillus subtilis, and compared to the classical analyses. This new method of analysis of the functional domain network reveals that a specific inhibition on the second domain of the lipoamide dehydrogenase (pdhD) component of pyruvate dehydrogenase complex leads to the loss of all fluxes. Such conclusion was not predictable in the classical approach.

Peres, Sabine; Felicori, Liza; Molina, Franck

2013-01-01

214

Combined insulin treatment and intense exercise training improved basal cardiac function and Ca(2+)-cycling proteins expression in type 1 diabetic rats.  

PubMed

This study investigated the effects of 8 weeks of intense exercise training combined with insulin treatment on the Ca(2+)-cycling protein complex expression and their functional consequences on cardiac function in type 1 diabetic rat hearts. Diabetic Wistar rats were randomly assigned into the following groups: received no treatment, insulin-treated diabetic, trained diabetic, and trained insulin-treated diabetic. A control group was also included. Insulin treatment and (or) treadmill intense exercise training were conducted over 8 weeks. Basal cardiac function was evaluated by Langendorff technique. Cardiac expression of the main Ca(2+)-cycling proteins (RyR2, FKBP 12.6, SERCA2, PLB, NCX1) was assessed by Western blot. Diabetes altered basal cardiac function (±dP/dt) and decrease the expression of the main Ca(2+)-cycling proteins expression: RyR2, SERCA2, and NCX1 (p < 0.05). Whereas combined treatment was not able to normalize -dP/dt, it succeeded to normalize +dP/dt of diabetic rats (p < 0.05). Moreover, both insulin and intense exercise training, applied solely, increased the expression of the Ca(2+)-cycling proteins: RyR2, SERCA2, PLB. and NCX1 (p < 0.05). But this effect was higher when the 2 treatments were combined. These data are the first to show that combined insulin treatment and intense exercise training during diabetes synergistically act on the expression of the main Ca(2+)-cycling proteins, providing insights into mechanisms by which the dual treatment during diabetes improves cardiac function. PMID:22185592

Le Douairon Lahaye, Solène; Gratas-Delamarche, Arlette; Malardé, Ludivine; Zguira, Sami; Vincent, Sophie; Lemoine Morel, Sophie; Carré, François; Rannou Bekono, Françoise

2012-02-01

215

Short-Term Mechanical Unloading With Left Ventricular Assist Devices After Acute Myocardial Infarction Conserves Calcium Cycling and Improves Heart Function  

PubMed Central

Objectives This study sought to demonstrate that short-term cardiac unloading with a left ventricular (LV) assist device (LVAD) after acute myocardial infarction (MI) can conserve calcium cycling and improve heart function. Background Heart failure secondary to MI remains a major source of morbidity and mortality. Alterations in calcium cycling are linked to cardiac dysfunction in the failing heart. Methods Adult Dorsett hybrid sheep underwent acute MI and were mechanically unloaded with an axial-flow LVAD (Impella 5.0) for 2 weeks (n = 6). Six sheep with MI only and 4 sham sheep were used as controls. All animals were followed for 12 weeks post-MI. Regional strains in the LV were measured by sonomicrometry. Major calcium-handling proteins (CHPs), including sarco-/endoplasmic reticulum calcium ATPase-2? (SERCA-2?), Na+-Ca2+ exchanger-1, and phospholamban, and Ca2+-ATPase activity were investigated. The electrophysiological calcium cycling in single isolated cardiomyocytes was measured with the patch-clamp technique. The related ultrastructures were studied with electron microscopy. Results LVAD unloading alleviated LV dilation and improved global cardiac function and regional contractility compared with the MI group. The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated compared with the MI group at 12 weeks. Impaired calcium cycling was evident in the adjacent noninfarcted zone in the MI group, whereas CHP expression was normalized and Ca2+-ATPase activity was preserved in the LVAD unloading group. The electrophysiological calcium cycling was also conserved, and the ultrastructural damage was ameliorated in the unloaded animals. Conclusions Short-term LVAD unloading may conserve calcium cycling and improve heart function during the post-infarct period.

Wei, Xufeng; Li, Tieluo; Hagen, Brian; Zhang, Pei; Sanchez, Pablo G.; Williams, Katrina; Li, Shuying; Bianchi, Giacomo; Son, Ho Sung; Wu, Changfu; DeFilippi, Christopher; Xu, Kai; Lederer, William J.; Wu, Zhongjun J.; Griffith, Bartley P.

2013-01-01

216

Analysis of the Prevalence, Secretion and Function of a Cell Cycle-Inhibiting Factor in the Melioidosis Pathogen Burkholderia pseudomallei  

PubMed Central

Enteropathogenic and enterohaemorrhagic Escherichia coli express a cell cycle-inhibiting factor (Cif), that is injected into host cells via a Type III secretion system (T3SS) leading to arrest of cell division, delayed apoptosis and cytoskeletal rearrangements. A homologue of Cif has been identified in Burkholderia pseudomallei (CHBP; Cif homologue in B. pseudomallei; BPSS1385), which shares catalytic activity, but its prevalence, secretion and function are ill-defined. Among 43 available B. pseudomallei genome sequences, 33 genomes (76.7%) harbor the gene encoding CHBP. Western blot analysis using antiserum raised to a synthetic CHBP peptide detected CHBP in 46.6% (7/15) of clinical B. pseudomallei isolates from the endemic area. Secretion of CHBP into bacterial culture supernatant could not be detected under conditions where a known effector (BopE) was secreted in a manner dependent on the Bsa T3SS. In contrast, CHBP could be detected in U937 cells infected with B. pseudomallei by immunofluorescence microscopy and Western blotting in a manner dependent on bsaQ. Unlike E. coli Cif, CHBP was localized within the cytoplasm of B. pseudomallei-infected cells. A B. pseudomallei chbP insertion mutant showed a significant reduction in cytotoxicity and plaque formation compared to the wild-type strain that could be restored by plasmid-mediated trans-complementation. However, there was no defect in actin-based motility or multinucleated giant cell formation by the chbP mutant. The data suggest that the level or timing of CHBP secretion differs from a known Bsa-secreted effector and that CHBP is required for selected virulence-associated phenotypes in vitro.

Pumirat, Pornpan; Broek, Charles Vander; Juntawieng, Niramol; Muangsombut, Veerachat; Kiratisin, Pattarachai; Pattanapanyasat, Kovit; Stevens, Joanne M.; Stevens, Mark P.; Korbsrisate, Sunee

2014-01-01

217

Thermochemical cycles  

NASA Technical Reports Server (NTRS)

The thermochemical production of hydrogen is described along with the HYDRGN computer program which attempts to rate the various thermochemical cycles. Specific thermochemical cycles discussed include: iron sulfur cycle; iron chloride cycle; and hybrid sulfuric acid cycle.

Funk, J. E.; Soliman, M. A.; Carty, R. H.; Conger, W. L.; Cox, K. E.; Lawson, D.

1975-01-01

218

Cisplatin-induced alterations in the functional spermatogonial stem cell pool and niche in C57/BL/6J mice following a clinically relevant multi-cycle exposure.  

PubMed

A typical clinical cis-diamminedichloroplatinum(II) (cisplatin) dosing regimen consists of repeated treatment cycles followed by a recovery period. While effective, this dosing structure results in a prolonged, often permanent, infertility in men. Spermatogonial stem cells (SSCs) are theoretically capable of repopulating the seminiferous tubules after exposure has ceased. We propose that an altered spermatogonial environment during recovery from the initial treatment cycle drives an increase in SSC mitotic cell activity, rendering the SSC pool increasingly susceptible to cisplatin-induced injury from subsequent cycles. To test this hypothesis, the undifferentiated spermatogonia population and niche of the adult mouse (C57/BL/6J) were examined during the recovery periods of a clinically-relevant cisplatin exposure paradigm. Histological examination revealed a disorganization of spermatogenesis correlating with the number of exposure cycles. Quantification of terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end labeling (TUNEL) staining indicated an increase in apoptotic frequency following exposure. Immunohistochemical examination of Foxo1 and incorporated BrdU showed an increase in the undifferentiated spermatogonial population and mitotic activity in the recovery period in mice exposed to one cycle, but not two cycles of cisplatin. Immunohistochemical investigation of glial cell line-derived neurotrophic factor (GDNF) revealed an increase in production along the basal Sertoli cell membrane throughout the recovery period in all treatment groups. Taken together, these data establish that the impact of cisplatin exposure on the functional stem cell pool and niche correlates with: (1) the number of dosing cycles; (2) mitotic activity of early germ cells; and (3) alterations in the basal Sertoli cell GDNF expression levels after cisplatin-induced testicular injury. PMID:24704392

Harman, James G; Richburg, John H

2014-06-01

219

Initial and equilibrium cycle evaluations of conversion and loading performance in light-water-moderated lattices as a function of fuel-to-coolant volume ratio (AWBA Development Program)  

Microsoft Academic Search

This report presents the results of an evaluation of performance of the U-Th and Pu-U238 fuel systems as a function of fuel-to-coolant volume ratio and as a function of cycle length (burnup) and power density. Results are included for both the initial cycle and the equilibrium cycle of operation. Only light water is considered as the coolant in this study.

N. R. Candelore; E. G. Johnson

1982-01-01

220

Linking sediment structure, hydrological functioning and biogeochemical cycling in disturbed coastal saltmarshes and implications for vegetation development  

NASA Astrophysics Data System (ADS)

Saltmarsh restoration undoubtedly provides environmental enhancement, with vegetation quickly re-establishing following the breach of sea walls and subsequent tidal inundation of previously defended areas. Yet evidence increasingly suggests that the restored saltmarshes do not have the same biological characteristics as their natural counterparts (Mossman et al. 2012) and this may be in part be due to physicochemical parameters at the site including anoxia and poor drainage. Hence, restored saltmarshes may not offer the range and quality of ecosystem services anticipated. These environments will have been 'disturbed' by previous land use and there is little understanding of the impacts of this disturbance on the wider hydrogeomorphic and biogeochemical functioning in restored saltmarshes and the implications for saltmarsh vegetation development. This study examines linkages between physical sediment characteristics, sediment structure (using X-ray microtomography), sub-surface hydrology (using pressure transducers and time series analysis), and sediment and porewater geochemistry (major and trace elements, major anions) in sediment cores collected from undisturbed saltmarshes and those restored by de-embankment. Sub-surface sediments in restored saltmarshes have lower organic matter content, lower moisture content and higher bulk density than undisturbed sites. Using X-ray tomography a clear horizon can be observed which separates relict agricultural soils at depth with less dense and structureless sediments deposited since de-embankment. Ratios of open to closed pore space suggest that while undisturbed saltmarshes have the highest porosity, restored saltmarshes have larger void spaces, but limited pore connectivity. Sub-surface hydrological response to tidal flooding was subdued in the restored compared to the undisturbed site, suggesting that porewater flow may be impeded. Time series analysis indicated that flow pathways differ in restored saltmarsh sediments with preferential horizontal flows. The undisturbed saltmarsh displayed typical vertical geochemical sediment profiles. However, in the restored sites total Fe and Mn are elevated at depth indicating an absence of diagenetic cycling, whilst porewater sulphate and nitrate increased at depth suggesting that vertical solute transport is impeded in restored sites. In surface sediments, though total Hg concentrations are similar, Hg methylation rates are significantly higher than in the undisturbed saltmarsh suggesting that surface anoxia and poor drainage may result in increased mobilization and bioavailability of Hg. These findings have implications for the wider biogeochemical ecosystem services offered by saltmarsh restoration and the water-logged, anoxic conditions produced are unsuitable for seedling germination and plant growth. This highlights the need for integrated understanding of physical and biogeochemical processes.

Spencer, Kate; Harvey, Gemma; James, Tempest; Simon, Carr; Michelle, Morris

2014-05-01

221

Function of metal-ion homeostasis in the cell division cycle, mitochondrial protein processing, sensitivity to mycobacterial infection and brain function.  

PubMed

A novel Saccharomyces cerevisiae mutant, unable to grow in the presence of 12.5 mmol l-1 EGTA, was isolated. The phenotype of the mutant is caused by a single amino acid change (Gly149 to Arg) in the essential yeast cell division cycle gene CDC1. The mutant could be suppressed by overexpression of the SMF1 gene, which codes for a plasma membrane Mn2+ transporter. We observed that the yeast SMF1 gene shares homology with the mouse Nramp gene. Nramp (Bcg) was cloned as a gene responsible for mouse resistance to infection with mycobacteria and is identical with the Ity and the Lsh genes conferring resistance to infection by Salmonella typhimurium and Leishmania donovani, respectively. Although the cloning of Nramp identified the gene responsible for the resistance of mice to mycobacteria, its function is unknown. We propose that the mammalian protein, like the yeast transporter, is a Mn2+ and/or Zn2+ transporter. Following the phagocytosis of a parasite into the phagosome, the macrophage produces reactive oxygen and/or nitrogen intermediates that are toxic for the internalized bacteria. The survival of the pathogen during the burst of macrophage respiratory activity is thought to be partly mediated by microbial superoxide dismutase (SOD), which contains Mn2+ or Fe2+ in its active centre. Nramp may transport Mn2+ from the extracellular milieu into the cytoplasm of a macrophage and, after the generation of the phagosome, remove Mn2+ from the organelle. Thus, the Mn(2+)-depletion of the phagosome microenvironment by the Nramp gene product may be a rate-limiting step in the metalloenzyme's production by the engulfed bacteria. This limitation will restrict the mycobacterial ability to produce active enzymes such as SOD and prevent the propagation of the ingested microorganisms. Conversely, an increased concentration of Mn2+ in the phagosome caused by a defective Nramp transporter (Bcgs) may promote the growth of the mycobacteria and render the organism sensitive to the pathogen. We use a similar approach to identify, clone and study other metal-ion transporters. PMID:9050240

Supek, F; Supekova, L; Nelson, H; Nelson, N

1997-01-01

222

Cassia tora L. (Jue-ming-zi) has anticancer activity in TCA8113 cells in vitro and exerts anti-metastatic effects in vivo  

PubMed Central

Cassia tora L. (Jue-ming-zi) is a traditional Chinese medicine widely used in East Asia. The in vitro anticancer effects of Jue-ming-zi were evaluated in TCA8113 human tongue carcinoma cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. At a concentration of 1.0 mg/ml, Cassia tora L. inhibited the growth of TCA8113 cells by 72%; this inhibiton was greater than that by 0.5 and 0.25 mg/ml Cassia tora L. (43 and 16%, respectively). To elucidate the inhibitory mechanisms underlying the anticancer effect of Cassia tora L. in cancer cells, the expression of genes associated with apoptosis, inflammation and metastasis were measured using RT-PCR and western blot analysis. Cassia tora L. significantly induced apoptosis in cancer cells (P<0.05) by upregulating Bax, caspase-3 and caspase-9, and by downregulating Bcl-2. The expression of genes associated with inflammation, including NF-?B, iNOS and COX-2, was significantly downregulated (P<0.05) by Cassia tora L., demonstrating its anti-inflammatory properties. Cassia tora L. also exerted a significant anti-metastatic effect on cancer cells as demonstrated by decreased mRNA expression of matrix metalloprotease (MMP) genes and increased expression of tissue inhibitors of metalloproteinases (TIMPs), and as confirmed by the inhibition of induced tumor metastasis induced in 26-M3.1 colon cells in BALB/c mice. Our results demonstrated that Cassia tora L. exhibited the most potent in vitro anticancer effects, induced apoptosis, had anti-inflammatory activities and exerted in vivo anti-metastatic effects. Additionally, the anticancer, anti-inflammatory and anti-metastatic effects of the higher Cassia tora L. concentrations were stronger compared with those of the lower Cassia tora L. concentrations tested.

ZHAO, XIN; WANG, QIANG; QIAN, YU; PANG, LIANG

2013-01-01

223

C1 metabolism and the Calvin cycle function simultaneously and independently during HCHO metabolism and detoxification in Arabidopsis thaliana treated with HCHO solutions.  

PubMed

Formaldehyde (HCHO) is suggested to be detoxified through one-carbon (C1) metabolism or assimilated by the Calvin cycle in plants. To further understand the function of the Calvin cycle and C1 metabolism in HCHO metabolism in plants, HCHO elimination and metabolism by Arabidopsis thaliana in HCHO solutions was investigated in this study. Results verified that Arabidopsis could completely eliminate aqueous HCHO from the HCHO solutions. Carbon-13 nuclear magnetic resonance ((13)C-NMR) analysis showed that H(13)CHO absorbed by Arabidopsis was first oxidized to H(13)COOH. Subsequently, a clear increase in [U-(13)C]Gluc peaks accompanied by a strong enhancement in peaks of [2-(13)C]Ser and [3-(13)C]Ser appeared in Arabidopsis. Pretreatment with cyclosporin A or L-carnitine, which might inhibit the transport of (13)C-enriched compounds into chloroplasts and mitochondria, caused a remarkable decline in yields of both [U-(13)C]Gluc and [3-(13)C]Ser in H(13)CHO-treated Arabidopsis. These results suggested that both the Calvin cycle and the C1 metabolism functioned simultaneously during HCHO detoxification. Moreover, both functioned more quickly under high H(13)CHO stress than low H(13)CHO stress. When a photorespiration mutant was treated in 6 mm H(13)CHO solution, formation of [U-(13)C]Gluc and [2-(13)C]Ser was completely inhibited, but generation of [3-(13)C]Ser was not significantly affected. This evidence suggested that the Calvin cycle and C1 metabolism functioned independently in Arabidopsis during HCHO metabolism. PMID:23421623

Song, Zhong-Bang; Xiao, Su-Qin; You, Lan; Wang, Sha-Sha; Tan, Hao; Li, Kun-Zhi; Chen, Li-Mei

2013-08-01

224

Stability of IRA-45 solid amine resin as a function of carbon dioxide absorption and steam desorption cycling  

NASA Technical Reports Server (NTRS)

The removal of CO2 from the NASA Space Station's cabin atmosphere, which may be undertaken by a solid-amine water (steam)-desorbed system, is presently evaluated with a view to long-term amine resin stability and adsorption/desorption cycling by means of an automated laboratory flow-testing facility. While the CO2-adsorption capacity of the IRA-45 amine resin used gradually decreased over time, the rate of degradation significantly decreased after the first 10 cycles. Attention is given to the presence (and possible need for removal) of trimethylamine in the process air downstream of the resin bed.

Wood, Peter C.; Wydeven, Theodore

1987-01-01

225

Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes  

Microsoft Academic Search

The endometrium plays a central role among the reproductive tissues in the context of early embryo-maternal communication and pregnancy. It undergoes typical changes during the sexual\\/oestrous cycle, which are regulated by the ovarian hormones progesterone and oestrogen. To identify the underlying molecular mechanisms we have performed the first holistic screen of transcriptome changes in bovine intercaruncular endometrium at two stages

S Bauersachs; S E Ulbrich; K Gross; SEM Schmidt; HHD Meyer; R Einspanier; H Wenigerkind; M Vermehren; H Blum; F Sinowatz; E Wolf

2005-01-01

226

Physiological variation in estradiol and brain function: A functional magnetic resonance imaging study of verbal memory across the follicular phase of the menstrual cycle  

Microsoft Academic Search

Women frequently complain of memory problems at times in their reproductive lives that are associated with changes in estrogen concentration (e.g. around menopause and childbirth). Further, behavioural studies suggest that memory performance may fluctuate across the menstrual cycle. For example, performance on verbal tasks has been reported to be greatest during phases associated with high estrogen concentrations whereas the opposite

Michael C. Craig; Paul C. Fletcher; Eileen M. Daly; Janice Rymer; Mick Brammer; Vincent Giampietro; Declan G. M. Murphy

2008-01-01

227

Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle.  

PubMed

Prenatal stress is associated with altered behavior and hypothalamic-pituitary-adrenal (HPA) axis function postnatally. Recent studies suggest that these outcomes are dependent on the timing of the prenatal stress. The majority of these studies have been carried out in male offspring. We hypothesized that a short period of prenatal stress would result in female offspring that exhibit differences in open-field behavior and HPA axis activity, but the outcome would depend on the timing of the prenatal stress and the stage of the reproductive cycle. Pregnant guinea pigs were exposed to a strobe light during the fetal brain growth spurt [gestational d 50-52 (PS50)] or during the period of rapid brain myelination [gestational d 60-62 (PS60)]. Open-field activity was assessed in juvenile and adult female offspring. HPA axis function was tested in adult offspring. All tests in adulthood were carried out during the estrous and luteal phases of the reproductive cycle to determine the effect of stage on HPA axis programming. Tissues were collected upon completion of the study for analysis by in situ hybridization. PS60 offspring exhibited decreased activity in an open field during the estrous phase of the reproductive cycle compared with control offspring. Both PS50 and PS60 offspring exhibited a lower salivary cortisol response to a stressor, only during the estrous phase. Consistent with the behavioral and endocrine data, PS60 females exhibited lower plasma estradiol levels, reduced ovary weight, and increased glucocorticoid receptor mRNA in the paraventricular nucleus. In conclusion, we have demonstrated that there are effects of prenatal stress on behavior and HPA axis functioning in female offspring but that the outcomes are dependent on the timing of the prenatal stress together with the status of the reproductive cycle. PMID:18755800

Kapoor, Amita; Matthews, Stephen G

2008-12-01

228

A new function of the splicing factor SRSF2 in the control of E2F1-mediated cell cycle progression in neuroendocrine lung tumors  

PubMed Central

The transcription factor E2F1 belongs to the E2F family and plays a crucial role during cell cycle progression and apoptosis. Ser/Arg-Rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. We previously identified the SR protein SRSF2 as a new transcriptional target of E2F1 and demonstrated that both proteins cooperate to induce apoptosis in non-small cell lung carcinoma. In this study, we postulated that SRSF2 is also involved in the proliferative functions of E2F1. Using IHC, we first demonstrate that SRSF2 and its phosphorylated form (P-SRSF2) are overexpressed in neuroendocrine lung tumors that are highly proliferative tumors expressing high levels of E2F1. Importantly, we show a direct correlation between cyclin E, an E2F1-target gene controlling S phase, and P-SRSF2 proteins levels (p = 0.0083), suggesting a role of SRSF2 in E2F1-mediated cellular proliferation. Accordingly, using neuroendocrine lung carcinoma cell lines, we demonstrate that SRSF2 is a cell cycle-regulated protein involved in entry and progression into S phase. We also provide evidence that SRSF2 interacts with E2F1 and stimulates its transcriptional control of cell cycle target genes such as cyclin E. Finally, we show that inhibition of AKT signaling pathway prevents SRSF2 phosphorylation and activity toward E2F1 transcriptional function. Taken together, these results identify a new role of SRSF2 in the control of cell cycle progression and reinforce the functional link between SRSF2 and E2F1 proteins.

Edmond, Valerie; Merdzhanova, Galina; Gout, Stephanie; Brambilla, Elisabeth; Gazzeri, Sylvie; Eymin, Beatrice

2013-01-01

229

Sensory screening for large-format natural corks by "dry soak" testing and its correlation to headspace solid-phase microextraction (SPME) gas chromatography/mass spectrometry (GC/MS) releasable trichloroanisole (TCA) analysis.  

PubMed

Large-format natural corks were individually screened for trichloroanisole (TCA) taint and other non-characteristic cork odors by smelling the high relative humidity headspace of the jarred closure during expert panel sensory sessions. The method was coined "dry soak sensory screening". Out of a population of 2296 corks, 138 specimens [6% of the total population (TP)] were retained because of unusual odors, ranging from mild to severe. All retained corks were analyzed for releasable TCA (RTCA) by the solid-phase microextraction (SPME) gas chromatography/mass spectrometry (GC/MS) technique. Results indicated that 30 corks (1.3% TP) had concentrations between 1.0 and 5.0 ppt. Most of these corks had non-typical TCA odors described as ashtray, musty, moldy, dirty, and wet cardboard. A total of 13 retained corks (0.57% TP) had RTCA values higher than 5.0 ppt, mostly displaying the typical TCA odor. Dry soak screening has been determined to be a clean, fast, and most importantly, a nondestructive method ideal for screening large-format natural corks with off odors. PMID:19722710

Macku, Carlos; Gonzalez, Lesa; Schleussner, Christiane; Mesquita, Ana Cristina; Herwatt, James W; Kirch, Leonard C; Schwartz, Rob J

2009-09-01

230

Changes in Sleep Time and Sleep Quality across the Ovulatory Cycle as a Function of Fertility and Partner Attractiveness  

PubMed Central

Research suggests that near ovulation women tend to consume fewer calories and engage in more physical activity; they are judged to be more attractive, express greater preferences for masculine and symmetrical men, and experience increases in sexual desire for men other than their primary partners. Some of these cycle phase shifts are moderated by partner attractiveness and interpreted as strategic responses to women's current reproductive context. The present study investigated changes in sleep across the ovulatory cycle, based on the hypothesis that changes in sleep may reflect ancestral strategic shifts of time and energy toward reproductive activities. Participants completed a 32-day daily diary in which they recorded their sleep time and quality for each day, yielding over 1,000 observations of sleep time and quality. Results indicated that, when the probability of conception was high, women partnered with less attractive men slept more, while women with more attractive partners slept less.

Goetz, Aaron T.

2014-01-01

231

Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae  

Microsoft Academic Search

Chromosomal replication initiates through the assembly of a prereplicative complex (pre-RC) at individual replication origins in the G1-phase, followed by activation of these complexes in the S-phase. In Saccharomyces cerevisiae , the origin recognition complex (ORC) binds replication ori- gins throughout the cell cycle and participates in pre-RC assembly. Whether the ORC plays an additional role subsequent to pre-RC assembly

Daniel G. Gibson; Stephen P. Bell; Oscar M. Aparicio

2006-01-01

232

Correlation between inflection of heart rate\\/work performance curve and myocardial function in exhausting cycle ergometer exercise  

Microsoft Academic Search

Summary  The heart rate\\/work performance (f\\u000ac\\/W) curve is usually S-shaped but a flattening at the top is not always seen. By means of radionuclide ventricular scintigraphy, the left ventricular ejection fraction (LVEF) of 15 sports students was investigated. The behaviour of the f\\u000ac\\/W curve during cycle ergometry with increasing exercise intensities was examined. During exercise, the LVEF showed a

R. Pokan; P. Hofmann; K. Preidler; H. Leitner; J. Dusleag; B. Eber; G. Schwaberger; G. F. Fiiger; W. Klein

1993-01-01

233

Cycle Inhibiting Factors (CIFs) Are a Growing Family of Functional Cyclomodulins Present in Invertebrate and Mammal Bacterial Pathogens  

PubMed Central

The cycle inhibiting factor (Cif) produced by enteropathogenic and enterohemorrhagic Escherichia coli was the first cyclomodulin to be identified that is injected into host cells via the type III secretion machinery. Cif provokes cytopathic effects characterized by G1 and G2 cell cycle arrests, accumulation of the cyclin-dependent kinase inhibitors (CKIs) p21waf1/cip1 and p27kip1 and formation of actin stress fibres. The X-ray crystal structure of Cif revealed it to be a divergent member of a superfamily of enzymes including cysteine proteases and acetyltransferases that share a conserved catalytic triad. Here we report the discovery and characterization of four Cif homologs encoded by different pathogenic or symbiotic bacteria isolated from vertebrates or invertebrates. Cif homologs from the enterobacteria Yersinia pseudotuberculosis, Photorhabdus luminescens, Photorhabdus asymbiotica and the ?-proteobacterium Burkholderia pseudomallei all induce cytopathic effects identical to those observed with Cif from pathogenic E. coli. Although these Cif homologs are remarkably divergent in primary sequence, the catalytic triad is strictly conserved and was shown to be crucial for cell cycle arrest, cytoskeleton reorganization and CKIs accumulation. These results reveal that Cif proteins form a growing family of cyclomodulins in bacteria that interact with very distinct hosts including insects, nematodes and humans.

Jubelin, Gregory; Chavez, Carolina Varela; Taieb, Frederic; Banfield, Mark J.; Samba-Louaka, Ascel; Nobe, Rika; Nougayrede, Jean-Philippe; Zumbihl, Robert; Givaudan, Alain; Escoubas, Jean-Michel; Oswald, Eric

2009-01-01

234

RNAi Targeting CXCR4 Inhibits Tumor Growth Through Inducing Cell Cycle Arrest and Apoptosis  

PubMed Central

CXC chemokine receptor 4 (CXCR4) is involved in many human malignant tumors and plays an important role in tumor growth and metastasis. To explore the effects of CXCR4 expression on the malignant cells of oral squamous cell carcinoma (OSCC), Tca8113 and SCC-9 cell lines, as well as their xenograft models, of nude mice were used to detect cancer cell proliferation alteration. This study also examined the corresponding molecular mechanism after CXCR4 knockdown using a recombinant lentiviral vector expressing small interference RNA (siRNA) for CXCR4. RNA interference-mediated knockdown of CXCR4 in highly aggressive (Tca8113 and SCC-9) tumor cells significantly inhibited the proliferation of the two cell lines in vitro and in vivo. The expression levels of >1,500 genes involved in cell cycle, apoptosis, and multiple signaling pathways were also altered. These results provide new evidence of CXCR4 as a promising tumor gene therapeutic target.

Yu, Tao; Wu, Yingying; Huang, Yi; Yan, Chaoran; Liu, Ying; Wang, Zongsheng; Wang, Xiaoyi; Wen, Yuming; Wang, Changmei; Li, Longjiang

2012-01-01

235

Carbon and nitrogen cycling in thermally heated sediments  

NASA Astrophysics Data System (ADS)

Hydrothermally heated sediment environments, such as are found in abundance throughout Yellowstone National Park, host fully functional microbial ecosystems. As with any ecosystem, both sources and sinks of carbon, nitrogen, and a myriad of other nutrients and energy-driving factors must be supplied. While we know microbial communities in hydrothermal environments can be surprisingly diverse, we know little about basic ecological functions such as carbon and nitrogen cycling. Previous work has shown that carbon cycling in one hot spring in Yellowstone National Park [“Bison Pool”] and its associated runoff channel functions as a complex system. Analysis of carbon and nitrogen isotopes in sediments and biofilms across a temperature and chemical gradient at this location revealed that the four best studied carbon fixation pathways [Calvin, reverse tricarboxylic acid, acetyl-CoA, 3-hydroxypropionate cycles] may all be functioning in this system, and nitrogen fixation varies across the chemosynthetic/photosynthetic ecotone [1]. Microcosm experiments using biofilms from this hot spring as inoculae with 13C labeled carbon substrates indicate heterotrophic growth [2]. In addition, metagenomic analysis of environmental DNA has indicated the presence of genes involved in carbon fixation [both phototrophic and autotrophic], and heterotrophy, as well as nitrogen fixation [3]. Studies from other Yellowstone locations have also found genetic evidence for carbon and nitrogen fixation [4, 5]. Of particular interest is the role of individuals in carbon and nitrogen cycling as environmental conditions suitable for chemosynthetic and photosynthetic growth vary. This study explores the diversity of cbbM/cbbL [Calvin cycle], aclB/oor/porA [rTCA cycle], nifH [nitrogen fixation], nirK [nitrite reduction] and amoA [ammonia oxidation] genes across a variety of Yellowstone environments. The transition of genetic diversity within sediments and biofilms is focused on the chemosynthetic/photosynthetic ecotone from a variety of hot springs spanning a range of pH and geochemical conditions. By sampling across this ecotone, changes in carbon and nitrogen fixation as a function of changing community structure become apparent. Environmental DNA was extracted from these samples, and the presence/absence of Bacteria and Archaea determined by PCR. In addition, PCR-directed screens reveal the presence or absence of the aforementioned functional genes. Further, comparison across a broad spectrum of environmental conditions supplies context for phylogenetic analysis of diversity. [1] Havig, J.R., 2009. Geochemistry of Hydrothermal Biofilms: Composition of Biofilms in Siliceous Sinter-Deposting Hot Springs. Doctoral Dissertation, Arizona State University. [2] Meyer-Dombard et al., 2007. Microbial Diversity and SIP Investigations of Streamer Biofilm Communities in Yellowstone. Goldschmidt Geochemical Conference. [3] Raymond et al., 2008. EOS Trans AGU. Abstract B14A-03. [4] Hall et al., 2008. AEM 74:4910-4922. [5] Steunou et al., 2006. PNAS 103:2398-2403.

Meyer-Dombard, D. R.; Burton, M.; Vennelakanti, S.; Havig, J. R.; Shock, E.

2009-12-01

236

In vivo 13C NMR Measurements of Cerebral Glutamine Synthesis as Evidence for Glutamate-Glutamine Cycling  

Microsoft Academic Search

The cerebral tricarboxylic acid (TCA) cycle rate and the rate of glutamine synthesis were measured in rats in vivo under normal physiological and hyperammonemic conditions using 13C NMR spectroscopy. In the hyperammonemic animals, blood ammonia levels were raised from control values of ≈ 0.05 mM to ≈ 0.35 mM by an intravenous ammonium acetate infusion. Once a steady-state of cerebral

N. R. Sibson; A. Dhankhar; G. F. Mason; K. L. Behar; D. L. Rothman; R. G. Shulman

1997-01-01

237

The importance of a highly active and DeltapH-regulated diatoxanthin epoxidase for the regulation of the PS II antenna function in diadinoxanthin cycle containing algae.  

PubMed

The present study focuses on the regulation of diatoxanthin (Dtx) epoxidation in the diadinoxanthin (Ddx) cycle containing algae Phaeodactylum tricornutum, Thalassiosira pseudonana, Cyclotella meneghiniana and Prymnesium parvum and its significance for the control of the photosystem II (PS II) antenna function. Our data show that Dtx epoxidase can exhibit extremely high activities when algal cells are transferred from high light (HL) to low light (LL). Under HL conditions, Dtx epoxidation is strongly inhibited by the light-driven proton gradient. Uncoupling of the cells during HL illumination restores the high epoxidation rates observed during LL. In Ddx cycle containing algae, non-photochemical quenching of chlorophyll fluorescence (NPQ) is directly correlated with the Dtx concentration and independent of the presence of the proton gradient. This means that a fast conversion of PS II from the heat dissipating state back to the light-harvesting state can only be realized by an efficient removal of the quenching pigment Dtx. It is proposed that the high Dtx epoxidation rates during LL illumination serve exactly this purpose. The inhibition of Dtx epoxidation by the DeltapH, on the other hand, ensures rapid increases in the Dtx concentration when photoprotection under conditions of HL illumination is required. The regulation of the PS II antenna function in Ddx cycle containing algae is different to that in violaxanthin (Vx) cycle containing plants, where for the zeaxanthin (Zx)-dependent NPQ the presence of a proton gradient is mandatory. In the green alga Chlorella vulgaris conversion of PS II from the heat dissipating state back to the light-harvesting state is controlled by the DeltapH, whose relaxation after a transition from HL to darkness or LL rapidly abolishes the thermal dissipation of excitation energy, including the Zx-dependent NPQ. Due to the inability of Zx to quench fluorescence in the absence of the DeltapH a fast epoxidation of Zx to Vx in LL is not needed and is missing in Chlorella vulgaris. PMID:16971213

Goss, Reimund; Ann Pinto, Elizabeth; Wilhelm, Christian; Richter, Michael

2006-10-01

238

Functional role for Sp1 in the transcriptional amplification of a cell cycle regulated histone H4 gene.  

PubMed

The promoter of the cell cycle regulated histone FO108 H4 gene is mediated by two in vivo protein/DNA interaction domains, sites I and II. We have shown previously that site II mediates the cell cycle controlled enhancement of H4 gene transcription at the G1/S phase boundary. Here we show that site I, an element containing both G-rich and ATF-like consensus sequences, confers maximal levels of transcription in proliferating cells. By the combined application of gel shift assays with site-directed mutagenesis, DNase I footprinting, oligonucleotide competition, in vitro expression of recombinant proteins, and specific antibody supershift studies, we demonstrate that the proximal G-rich sequence within site I interacts with the transcription factor Sp1, while the distal portion of site I interacts with members of the ATF family of proteins, including ATF-1. In vitro transcription studies as well as expression assays of transiently and stably transfected genes in HeLa cells reveal that the deletion of site I causes a dramatic decrease in expression. Mutation of the Sp1 element, which abolishes Sp1 binding, results in a 6-10-fold reduction in reporter activity. In addition, overexpression of Sp1 in Sp1-deficient cells results in the dramatic activation of the histone promoter. In contrast, mutation of the asymmetric ATF binding site, located distally within site I, has a more limited effect upon expression. Interestingly, the contribution of the Sp1 site to maximal transcription was cell type dependent. Thus, we demonstrate that the Sp1 binding site of the site I histone H4 promoter in particular is critical for maximal expression in living cells and postulate that this site may act to amplify the cell cycle response. PMID:7779811

Birnbaum, M J; Wright, K L; van Wijnen, A J; Ramsey-Ewing, A L; Bourke, M T; Last, T J; Aziz, F; Frenkel, B; Rao, B R; Aronin, N

1995-06-13

239

Rock Cycle: Cycling  

NSDL National Science Digital Library

This Science Object is the third of four Science Objects in the Rocks SciPack. It explores the variables that contribute to rock transformation and the continuous processes of rock formation that constitute the rock cycle. The rock cycle provides an example of the transfer of energy and mass in the Earth system. Earth is a closed system containing essentially a fixed amount of each element. Movement of matter is driven by the Earth's internal and external sources of energy, and is often accompanied by changes in the physical and chemical properties of the matter. Minerals are made, dissolved, and remade--on the Earth's surface, in the oceans, and in the hot, high-pressure layers beneath the crust. The total amount of material stays the same as its forms change. Learning Outcomes:� Recognize the formation and transformation processes as part of a continuing cycle.� Identify that while the form and location of different rocks change over time, the amount of material and the distribution among the elements remains constant.� Explain the different processes or paths that each type of rock may take in the rock cycle.

National Science Teachers Association (NSTA)

2006-11-01

240

Life Cycles  

NSDL National Science Digital Library

Students extend their knowledge of matter and energy cycles in organisms to engineering life cycle assessment of products. They learn about product life cycle assessment and the flow of energy through the cycle, comparing it to the flow of nutrients and energy in the life cycles of organisms.

Integrated Teaching And Learning Program

241

Effects of Potent Inhibitors of the Retinoid Cycle on Visual Function and Photoreceptor Protection from Light Damage in MiceS  

PubMed Central

Regeneration of the chromophore 11-cis-retinal is essential for the generation of light-sensitive visual pigments in the vertebrate retina. A deficiency in 11-cis-retinal production leads to congenital blindness in humans; however, a buildup of the photoisomerized chromophore can also be detrimental. Such is the case when the photoisomerized all-trans-retinal is produced but cannot be efficiently cleared from the internal membrane of the outer segment discs. Sustained increase of all-trans-retinal can lead to the formation of toxic condensation products in the eye. Thus, there is a need for potent, selective inhibitors that can regulate the flux of retinoids through the metabolism pathway termed the visual (retinoid) cycle. Here we systematically study the effects of the most potent inhibitor of this cycle, retinylamine (Ret-NH2), on visual function in mice. Prolonged, sustainable, but reversible suppression of the visual function was observed by Ret-NH2 as a result of its storage in a prodrug form, N-retinylamides. Direct comparison of other inhibitors such as fenretinide and 13-cis-retinoic acid showed multiple advantages of Ret-NH2 and its amides, including a higher potency, specificity, and lower transcription activation. Our results also revealed that mice treated with Ret-NH2 were completely resistant to the light-induced retina damage. As an experimental tool, Ret-NH2 allows the replacement of the native chromophore with synthetic analogs in wild-type mice to better understand the function of the chromophore in the activation of rhodopsin and its metabolism through the retinoid cycle.

Maeda, Akiko; Maeda, Tadao; Golczak, Marcin; Imanishi, Yoshikazu; Leahy, Patrick; Kubota, Ryo; Palczewski, Krzysztof

2014-01-01

242

Global Analysis of Host Cell Gene Expression Late during Cytomegalovirus Infection Reveals Extensive Dysregulation of Cell Cycle Gene Expression and Induction of Pseudomitosis Independent of US28 Function  

PubMed Central

Replication of human cytomegalovirus (CMV) depends on host cell gene products working in conjunction with viral functions and leads to a dramatic dysregulation of cell cycle gene expression. Comprehensive transcriptional profiling was used to identify pathways most dramatically modulated by CMV at late times during infection and to determine the extent to which expression of the viral chemokine receptor US28 contributed to modulating cellular gene expression. Cells infected with the AD169 strain of virus or a fully replication competent US28-deficient derivative (RV101) were profiled throughout the late phase of infection (50, 72, and 98 h postinfection). Although sensitive statistical analysis showed striking global changes in transcript levels in infected cells compared to uninfected cells, the expression of US28 did not contribute to these alterations. CMV infection resulted in lower levels of transcripts encoding cytoskeletal, extracellular matrix, and adhesion proteins, together with small GTPases and apoptosis regulators, and in higher levels of transcripts encoding cell cycle, DNA replication, energy production, and inflammation-related gene products. Surprisingly, a large number of cellular transcripts encoding mitosis-related proteins were upmodulated at late times in infection, and these were associated with the formation of abnormal mitotic spindles and the appearance of pseudomitotic cells. These data extend our understanding of how broadly CMV alters the regulation of host cell cycle gene products and highlight the establishment of a mitosis-like environment in the absence of cellular DNA replication as important for viral replication and maturation.

Hertel, Laura; Mocarski, Edward S.

2004-01-01

243

Laboratory batch experiments of the combined effects of ultrasound and air stripping in removing CCl4 and 1,1,1-TCA from water.  

PubMed

Ultrasonic and air-stripping techniques for removal of carbon tetrachloride (CCl4) and 1,1,1-trichloroethane (1,1,1-TCA) from water were studied in batch experiments. Ultrasound (US) is effective for destroying organic compounds in aqueous solutions whereas air stripping (AS) efficiently transfers volatile compounds from the liquid to the gas phase. In simultaneous US and AS experiments, synergistic effects were observed and attributed to the effect of US on the mass transfer process. Using a photographic method, ultrasonic break up of gas bubbles and changes in gas holdup ratios were examined. In the two different gas-sparging systems studied, ultrasonic waves did not break up gas bubbles. In contrast, bubbles from the smaller porous size diffuser were coalesced due to sonication. In addition, both photographic and gas holdup experiments demonstrated that ultrasonic irradiation increased the gas holdup ratio. The enhancement observed in the removal of the compounds appeared to be due to this greater ultrasonic gas holdup ratio. PMID:15811676

Ayyildiz, Onder; Anderson, Paul R; Peters, Robert W

2005-04-11

244

Code Calibration Applied to the TCA High-Lift Model in the 14 x 22 Wind Tunnel (Simulation With and Without Model Post-Mount)  

NASA Technical Reports Server (NTRS)

The objective of this study is to calibrate a Navier-Stokes code for the TCA (30/10) baseline configuration (partial span leading edge flaps were deflected at 30 degs. and all the trailing edge flaps were deflected at 10 degs). The computational results for several angles of attack are compared with experimental force, moments, and surface pressures. The code used in this study is CFL3D; mesh sequencing and multi-grid were used to full advantage to accelerate convergence. A multi-grid approach was used similar to that used for the Reference H configuration allowing point-to-point matching across all the trailingedge block interfaces. From past experiences with the Reference H (ie, good force, moment, and pressure comparisons were obtained), it was assumed that the mounting system would produce small effects; hence, it was not initially modeled. However, comparisons of lower surface pressures indicated the post mount significantly influenced the lower surface pressures, so the post geometry was inserted into the existing grid using Chimera (overset grids).

Lessard, Wendy B.

1999-01-01

245

Solar activity secular cycles  

NASA Astrophysics Data System (ADS)

Long-term variations in solar activity secular cycles have been studied using a method for the expansion of reconstructed sunspot number series Sn( t) for 11400 years in terms of natural orthogonal functions. It has been established that three expansion components describe more than 98% of all Sn( t) variations. In this case, the contribution of the first expansion component is about 92%. The averaged form of the 88year secular cycle has been determined based on the form of the first expansion coordinate function. The quasi-periodicities modulating the secular cycle have been revealed based on the time function conjugate to the first function. The quasi-periodicities modulating the secular cycle coincide with those observed in the Sn( t) series spectrum. A change in the secular cycle form and the time variations in this form are described by the second and third expansion components, the contributions of which are about 4 and 2%, respectively. The variations in the steepness of the secular cycle branches are more pronounced in the 200-year cycle, and the secular cycle amplitude varies more evidently in the 2300-year cycle.

Kramynin, A. P.; Mordvinov, A. V.

2013-12-01

246

Proteome-based comparative analyses of growth stages reveal new cell cycle-dependent functions in the predatory bacterium Bdellovibrio bacteriovorus.  

PubMed

Bdellovibrio and like organisms are obligate predators of bacteria that are ubiquitously found in the environment. Most exhibit a peculiar dimorphic life cycle during which free-swimming attack-phase (AP) cells search for and invade bacterial prey cells. The invader develops in the prey as a filamentous polynucleoid-containing cell that finally splits into progeny cells. Therapeutic and biocontrol applications of Bdellovibrio in human and animal health and plant health, respectively, have been proposed, but more knowledge of this peculiar cell cycle is needed to develop such applications. A proteomic approach was applied to study cell cycle-dependent expression of the Bdellovibrio bacteriovorus proteome in synchronous cultures of a facultative host-independent (HI) strain able to grow in the absence of prey. Results from two-dimensional gel electrophoresis, mass spectrometry, and temporal expression of selected genes in predicted operons were analyzed. In total, about 21% of the in silico predicted proteome was covered. One hundred ninety-six proteins were identified, including 63 hitherto unknown proteins and 140 life stage-dependent spots. Of those, 47 were differentially expressed, including chemotaxis, attachment, growth- and replication-related, cell wall, and regulatory proteins. Novel cell cycle-dependent adhesion, gliding, mechanosensing, signaling, and hydrolytic functions were assigned. The HI model was further studied by comparing HI and wild-type AP cells, revealing that proteins involved in DNA replication and signaling were deregulated in the former. A complementary analysis of the secreted proteome identified 59 polypeptides, including cell contact proteins and hydrolytic enzymes specific to predatory bacteria. PMID:18836011

Dori-Bachash, Mally; Dassa, Bareket; Pietrokovski, Shmuel; Jurkevitch, Edouard

2008-12-01

247

Hsp70 and Hsp40 Functionally Interact with Soluble Mutant Huntingtin Oligomers in a Classic ATP-dependent Reaction Cycle*  

PubMed Central

Inclusion bodies of aggregated mutant huntingtin (htt) fragments are a neuropathological hallmark of Huntington disease (HD). The molecular chaperones Hsp70 and Hsp40 colocalize to inclusion bodies and are neuroprotective in HD animal models. How these chaperones suppress mutant htt toxicity is unclear but might involve direct effects on mutant htt misfolding and aggregation. Using size exclusion chromatography and atomic force microscopy, we found that mutant htt fragments assemble into soluble oligomeric species with a broad size distribution, some of which reacted with the conformation-specific antibody A11. Hsp70 associated with A11-reactive oligomers in an Hsp40- and ATP-dependent manner and inhibited their formation coincident with suppression of caspase 3 activity in PC12 cells. Thus, Hsp70 and Hsp40 (DNAJB1) dynamically target specific subsets of soluble oligomers in a classic ATP-dependent reaction cycle, supporting a pathogenic role for these structures in HD.

Lotz, Gregor P.; Legleiter, Justin; Aron, Rebecca; Mitchell, Emily J.; Huang, Shao-Yi; Ng, Cheping; Glabe, Charles; Thompson, Leslie M.; Muchowski, Paul J.

2010-01-01

248

Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle.  

PubMed

Inclusion bodies of aggregated mutant huntingtin (htt) fragments are a neuropathological hallmark of Huntington disease (HD). The molecular chaperones Hsp70 and Hsp40 colocalize to inclusion bodies and are neuroprotective in HD animal models. How these chaperones suppress mutant htt toxicity is unclear but might involve direct effects on mutant htt misfolding and aggregation. Using size exclusion chromatography and atomic force microscopy, we found that mutant htt fragments assemble into soluble oligomeric species with a broad size distribution, some of which reacted with the conformation-specific antibody A11. Hsp70 associated with A11-reactive oligomers in an Hsp40- and ATP-dependent manner and inhibited their formation coincident with suppression of caspase 3 activity in PC12 cells. Thus, Hsp70 and Hsp40 (DNAJB1) dynamically target specific subsets of soluble oligomers in a classic ATP-dependent reaction cycle, supporting a pathogenic role for these structures in HD. PMID:20864533

Lotz, Gregor P; Legleiter, Justin; Aron, Rebecca; Mitchell, Emily J; Huang, Shao-Yi; Ng, Cheping; Glabe, Charles; Thompson, Leslie M; Muchowski, Paul J

2010-12-01

249

Function of the pentose phosphate pathway and its key enzyme, transketolase, in the regulation of the meiotic cell cycle in oocytes  

PubMed Central

Objective Previously, we identified that transketolase (Tkt), an important enzyme in the pentose phosphate pathway, is highly expressed at 2 hours of spontaneous maturation in oocytes. Therefore, this study was performed to determine the function of Tkt in meiotic cell cycle regulation, especially at the point of germinal vesicle breakdown (GVBD). Methods We evaluated the loss-of-function of Tkt by microinjecting Tkt double-stranded RNAs (dsRNAs) into germinal vesicle-stage oocytes, and the oocytes were cultured in vitro to evaluate phenotypic changes during oocyte maturation. In addition to maturation rates, meiotic spindle and chromosome rearrangements, and changes in expression of other enzymes in the pentose phosphate pathway were determined after Tkt RNA interference (RNAi). Results Despite the complete and specific knockdown of Tkt expression, GVBD occurred and meiosis was arrested at the metaphase I (MI) stage. The arrested oocytes exhibited spindle loss, chromosomal aggregation, and declined maturation promoting factor and mitogen-activated protein kinase activities. The modified expression of two enzymes in the pentose phosphate pathway, Prps1 and Rbks, after Tkt RNAi and decreased maturation rates were amended when ribose-5-phosphate was supplemented in the culture medium, suggesting that the Tkt and pentose phosphate pathway are important for the maturation process. Conclusion We concluded that Tkt and its associated pentose phosphate pathway play an important role in the MI-MII transition of the oocytes' meiotic cell cycle, but not in the process of GVBD.

Kim, Yunna; Kim, Eun-Young; Seo, You-Mi; Yoon, Tae Ki; Lee, Woo-Sik

2012-01-01

250

Sometimes "Newton's Method" Always "Cycles"  

ERIC Educational Resources Information Center

Are there functions for which Newton's method cycles for all non-trivial initial guesses? We construct and solve a differential equation whose solution is a real-valued function that two-cycles under Newton iteration. Higher-order cycles of Newton's method iterates are explored in the complex plane using complex powers of "x." We find a class of…

Latulippe, Joe; Switkes, Jennifer

2012-01-01

251

Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function  

PubMed Central

Aims Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. Methods and results MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100% O2, 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI + HBO), MSC (MI + MSC), and MSC + Ox (MI + MSC + HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC + Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC + Ox group compared with the MI group. Conclusions The results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression.

Khan, Mahmood; Meduru, Sarath; Gogna, Rajan; Madan, Esha; Citro, Lucas; Kuppusamy, Muthulakshmi L.; Sayyid, Muzzammil; Mostafa, Mahmoud; Hamlin, Robert L.; Kuppusamy, Periannan

2012-01-01

252

Beneficial function of cell division cycle 2 activity in astrocytes on axonal regeneration after spinal cord injury.  

PubMed

Migrating activity of reactive astrocytes induced after spinal cord injury (SCI) controls glial scar formation by limiting inflammatory responses around the injury area, and, therefore, can be beneficial for regenerative responses of spinal axons. Recently, we found that cell division cycle 2 (cdc2) activity in primary astrocytes facilitated neurite outgrowth of co-cultured neurons. Here, we investigated the effects of cdc2 activity on regenerative processes in vivo after SCI. Administration of the cdc2 inhibitor purvalanol A restricted compaction of the injury cavity and astrocyte infiltration into the cavity. After SCI, regenerative responses of anterogradely labeled corticospinal tract (CST) axons were attenuated by purvalanol A treatment. Using the polymeric tube that was implanted into the spinal cord as a nerve guide conduit, we found that purvalanol A treatments reduced astrocyte migration into the tube graft and, in parallel, retarded the extension of spinal axons into the tube. These results suggest that astrocytes with cdc2 activity may play a permissive role in mediating regrowth of spinal axons after lesion. PMID:23360302

Seo, Tae Beom; Chang, In Ae; Lee, Jin Ho; Namgung, Uk

2013-06-15

253

The Flux of Open and Torroidal Interplanetary Magnetic Field as a Function of Heliolatitude and Solar Cycle  

NASA Astrophysics Data System (ADS)

Analyses performed during the previous 11-year phase of the solar cycle attempted to measure the flux of open and toroidal magnetic field lines [Bieber and Rust, ApJ, 453, 911, 1995] and associate the toroidal flux with coronal mass ejections (CMEs) [Smith and Phillips, JGR, 102, 249, 1997]. Since that time Ulysses has made three polar passes and spent at least eight years at polar latitudes, enabling us to examine the underlying assumption of the earlier studies that using near-ecliptic latitude measurements could serve as a proxy for polar-latitude observations. We find confirmation of the claims that the present solar minimum has experienced a strong decrease in open flux, but we also find evidence of past conditions at this same level. We find that torroidal flux is virtually negligable at higher latitudes as measured by the Ulysses spacecraft, even during times of solar maximum, and attribute this to the sub-photospheric winding of the Sun's magnetic field as illustrated by the familiar butterfly diagram. Our observations of the rate of toroidal flux ejection, 7 × 1022 Mx/year, sets a lower limit on the amount of magnetic flux that can be ejected by CMEs near solar maximum.

Connick, D. E.; Smith, C. W.; Schwadron, N. A.

2008-12-01

254

SLC\\/Exodus2\\/6Ckine\\/TCA4 induces chemotaxis of hematopoietic progenitor cells: differential activity of ligands of CCR7, CXCR3, or CXCR4 in chemotaxis vs. suppression of progenitor proliferation  

Microsoft Academic Search

Chemokines induce chemotaxis of hema- topoietic progenitor cells (HPC), and suppress their proliferation. In this study we report that SLC\\/ Exodus2\\/6Ckine\\/TCA4 (hereafter termed SLC) is a chemoattractant for human CD341 HPC. SLC mainly induces preferential chemotaxis of macro- phage progenitors. We examined the chemotactic activity of CXCR3 ligands on CD341 HPC because it has been reported that SLC is a

Chang H. Kim; Hal E. Broxmeyer

255

Purple bamboo salt has anticancer activity in TCA8113 cells in vitro and preventive effects on buccal mucosa cancer in mice in vivo  

PubMed Central

Bamboo salt is a traditional healthy salt known in Korea. The in vitro anticancer effects of the salt were evaluated using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay in TCA8113 human tongue carcinoma cells. At 1% concentration, the growth inhibitory rate of purple bamboo salt was 61% higher than that of sea salt (27%). Apoptosis analysis of the cancer cells was carried out using 4,6-diamidino-2-phenylindole (DAPI) staining to investigate the mechanism of the anticancer effects in tongue carcinoma cells. Purple bamboo salt induced a stronger apoptotic effect than sea salt. An Institute of Cancer Research (ICR) mouse buccal mucosa cancer model was established by injecting mice with U14 squamous cell carcinoma cells. Following injection, the wound at the injection site was smeared with salt samples. It was observed that the tumor volumes for the group treated with purple bamboo salt were smaller than those from the sea salt treatment and control groups. The sections of buccal mucosa cancer tissue showed that canceration in the purple bamboo salt group was weaker compared with that in the sea salt group. Similar results were observed in the lesion section of the cervical lymph. Using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, the purple bamboo salt group demonstrated an increase in Bcl-2-associated X protein (Bax) and a decrease in B cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, compared with the sea salt and control groups. The results demonstrated that purple bamboo salt had improved in vivo buccal mucosa cancer preventive activity compared with sea salt in mice.

ZHAO, XIN; DENG, XIAOXIAO; PARK, KUN-YOUNG; QIU, LIHUA; PANG, LIANG

2013-01-01

256

Menstrual Cycle: Basic Biology  

PubMed Central

The basic biology of the menstrual cycle is a complex, coordinated sequence of events involving the hypothalamus, anterior pituitary, ovary, and endometrium. The menstrual cycle with all its complexities can be easily perturbed by environmental factors such as stress, extreme exercise, eating disorders, and obesity. Furthermore, genetic influences such as fragile X premutations (Chapter X), X chromosome abnormalities (Chapter X), and galactose-1-phosphate uridyltransferase (GALT) point mutations (galactosemia) also contribute to perturbations of the menstrual cycle. Although not perfect, mouse model have helped to identify and confirm additional components and pathways in menstrual cycle function and dysfunction in humans.

Hawkins, Shannon M.; Matzuk, Martin M.

2010-01-01

257

SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth  

PubMed Central

An increasing number of genes predisposing to autism spectrum disorders (ASDs) has been identified, many of which are implicated in synaptic function. This ‘synaptic autism pathway’ notably includes disruption of SYN1 that is associated with epilepsy, autism and abnormal behavior in both human and mice models. Synapsins constitute a multigene family of neuron-specific phosphoproteins (SYN1-3) present in the majority of synapses where they are implicated in the regulation of neurotransmitter release and synaptogenesis. Synapsins I and II, the major Syn isoforms in the adult brain, display partially overlapping functions and defects in both isoforms are associated with epilepsy and autistic-like behavior in mice. In this study, we show that nonsense (A94fs199X) and missense (Y236S and G464R) mutations in SYN2 are associated with ASD in humans. The phenotype is apparent in males. Female carriers of SYN2 mutations are unaffected, suggesting that SYN2 is another example of autosomal sex-limited expression in ASD. When expressed in SYN2 ?knockout neurons, wild-type human Syn II fully rescues the SYN2 knockout phenotype, whereas the nonsense mutant is not expressed and the missense mutants are virtually unable to modify the SYN2 knockout phenotype. These results identify for the first time SYN2 ?as a novel predisposing gene for ASD and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies ASD.

Corradi, Anna; Fadda, Manuela; Piton, Amelie; Patry, Lysanne; Marte, Antonella; Rossi, Pia; Cadieux-Dion, Maxime; Gauthier, Julie; Lapointe, Line; Mottron, Laurent; Valtorta, Flavia; Rouleau, Guy A.; Fassio, Anna; Benfenati, Fabio; Cossette, Patrick

2014-01-01

258

SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic vesicle cycling and axon outgrowth.  

PubMed

An increasing number of genes predisposing to autism spectrum disorders (ASDs) has been identified, many of which are implicated in synaptic function. This 'synaptic autism pathway' notably includes disruption of SYN1 that is associated with epilepsy, autism and abnormal behavior in both human and mice models. Synapsins constitute a multigene family of neuron-specific phosphoproteins (SYN1-3) present in the majority of synapses where they are implicated in the regulation of neurotransmitter release and synaptogenesis. Synapsins I and II, the major Syn isoforms in the adult brain, display partially overlapping functions and defects in both isoforms are associated with epilepsy and autistic-like behavior in mice. In this study, we show that nonsense (A94fs199X) and missense (Y236S and G464R) mutations in SYN2 are associated with ASD in humans. The phenotype is apparent in males. Female carriers of SYN2 mutations are unaffected, suggesting that SYN2 is another example of autosomal sex-limited expression in ASD. When expressed in SYN2 ?knockout neurons, wild-type human Syn II fully rescues the SYN2 knockout phenotype, whereas the nonsense mutant is not expressed and the missense mutants are virtually unable to modify the SYN2 knockout phenotype. These results identify for the first time SYN2 ?as a novel predisposing gene for ASD and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies ASD. PMID:23956174

Corradi, Anna; Fadda, Manuela; Piton, Amélie; Patry, Lysanne; Marte, Antonella; Rossi, Pia; Cadieux-Dion, Maxime; Gauthier, Julie; Lapointe, Line; Mottron, Laurent; Valtorta, Flavia; Rouleau, Guy A; Fassio, Anna; Benfenati, Fabio; Cossette, Patrick

2014-01-01

259

Methanol to olefin Conversion on HSAPO-34 zeolite from periodic density functional theory calculations: a complete cycle of side chain hydrocarbon pool mechanism  

SciTech Connect

For its unique position in the coal chemical industry, the methanol to olefin (MTO) reaction has been a hot topic in zeolite catalysis. Due to the complexities of catalyst structure and reaction networks, many questions such as how the olefin chain is built from methanol remain elusive. On the basis of periodic density functional theory calculations, this work establishes the first complete catalytic cycle for MTO reaction via hexamethylbenzene (HMB) trapped in HSAPO-34 zeolite based on the so-called side chain hydrocarbon pool mechanism. The cycle starts from the methylation of HMB that leads to heptamethylbenzenium ion (heptaMB{sup +}) intermediate. This is then followed by the growth of side chain via repeated deprotonation of benzenium ions and methylation of the exocyclic double bond. Ethene and propene can finally be released from the side ethyl and isopropyl groups of benzenium ions by deprotonation and subsequent protonation steps. We demonstrate that (i) HMB/HSAPO-34 only yields propene as the primary product based on the side chain hydrocarbon pool mechanism and (ii) an indirect proton-shift step mediated by water that is always available in the system is energetically more favorable than the traditionally regarded internal hydrogen-shift step. Finally, the implications of our results toward understanding the effect of acidity of zeolite on MTO activity are also discussed.

Wang, C.M.; Wang, Y.D.; Xie, Z.K.; Liu, Z.P. [SINOPEC, Shanghai (China)

2009-03-15

260

The trophic biology of the holothurian Molpadia musculus: implications for organic matter cycling and ecosystem functioning in a deep submarine canyon  

NASA Astrophysics Data System (ADS)

Megafaunal organisms play a key role in ecosystem functioning in the deep-sea through bioturbation, bioirrigation and organic matter cycling. At 3500 m water depth in the Nazaré Canyon, NE Atlantic, very high abundances of the infaunal holothurian Molpadia musculus were observed. To quantify the role of M. musculus in sediment cycling, sediment samples and holothurians were collected using an ROV and in situ experiments were conducted with incubation chambers. The biochemical composition of the sediment (in terms of proteins, carbohydrates and lipids), the holothurians' gut contents and holothurians' faecal material were analysed. In the sediments, proteins were the dominant organic compound, followed by carbohydrates and lipids. In the holothurian's gut contents, protein concentrations were higher than the other compounds, decreasing significantly as the material passed through the digestive tract. Approximately 33±1% of the proteins were digested by the time sediment reached the mid gut, with a total digestion rate equal to 67±1%. Carbohydrates and lipids were ingested in smaller amounts and digested with lower efficiencies (23±11% and 50±11%, respectively). As a result, the biopolymeric C digestion rate was on average 62±3%. We estimated that the population of M. musculus could remove approximately 0.49±0.13 g biopolymeric C and 0.13±0.03 g N m-2 d-1 from the sediments. These results suggest that M. musculus plays a key role in the benthic tropho-dynamics and biogeochemical processes in the Nazaré Canyon.

Amaro, T.; Bianchelli, S.; Billett, D. S. M.; Cunha, M. R.; Pusceddu, A.; Danovaro, R.

2010-08-01

261

Discover the Solar Cycle  

NSDL National Science Digital Library

This is an activity about the periodicity of the solar cycle. Learners will calculate the number of M-class solar flares as a percentage of the total number of X-ray solar flares and graph these results as a function of time. When compared to a graph of the number of sunspots as a function of time, learners make conclusions about the period of the solar cycle. This activity uses data from the Geostationary Operational Environmental Satellite (GOES).

262

Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes  

PubMed Central

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted LC/MS/MS to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Leprdb; db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve and DRG from diabetic mice. Utilizing LC/ESI/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids, HODEs) in db/db tissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerve to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

Hinder, Lucy M.; Vivekanandan-Giri, Anuradha; McLean, Lisa L.; Pennathur, Subramaniam; Feldman, Eva L.

2013-01-01

263

Mice Deficient for the Wild-Type p53-Induced Phosphatase Gene (Wip1) Exhibit Defects in Reproductive Organs, Immune Function, and Cell Cycle Control  

PubMed Central

The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNA-damaging agents. We show here that Wip1 message is expressed in moderate levels in all organs, but is present at very high levels in the testes, particularly in the postmeiotic round spermatid compartment of the seminiferous tubules. We have confirmed that Wip1 mRNA is induced by ionizing radiation in mouse tissues in a p53-dependent manner. To further determine the normal biological function of Wip1 in mammalian organisms, we have generated Wip1-deficient mice. Wip1 null mice are viable but show a variety of postnatal abnormalities, including variable male runting, male reproductive organ atrophy, reduced male fertility, and reduced male longevity. Mice lacking Wip1 show increased susceptibility to pathogens and diminished T- and B-cell function. Fibroblasts derived from Wip1 null embryos have decreased proliferation rates and appear to be compromised in entering mitosis. The data are consistent with an important role for Wip1 in spermatogenesis, lymphoid cell function, and cell cycle regulation.

Choi, Jene; Nannenga, Bonnie; Demidov, Oleg N.; Bulavin, Dmitry V.; Cooney, Austin; Brayton, Cory; Zhang, Yongxin; Mbawuike, Innocent N.; Bradley, Allan; Appella, Ettore; Donehower, Lawrence A.

2002-01-01

264

Rock Cycle  

NSDL National Science Digital Library

This interactive Flash animation about the rock cycle is suitable for a review or overview in an introductory level Physical Geology class. It includes animations, photos, and descriptions involving rock types and processes in the rock cycle.

Smoothstone; Company, Houghton M.

265

Menstrual Cycle  

MedlinePLUS

... This information in Spanish ( en español ) The menstrual cycle Day 1 starts with the first day of ... levels drop at the end of the previous cycle, signaling blood and tissues lining the uterus (womb) ...

266

Biogeochemical Cycling  

NASA Technical Reports Server (NTRS)

This lecture will introduce the concept of biogeochemical cycling. The roles of microbes in the cycling of nutrients, production and consumption of trace gases, and mineralization will be briefly introduced.

Bebout, Brad; Fonda, Mark (Technical Monitor)

2002-01-01

267

Restoration of Mechanical and Energetic Function in Failing Aortic-Banded Rat Hearts by Gene Transfer of Calcium Cycling Proteins  

PubMed Central

The aim of this study was to examine whether short- and long-term gene transfer of Ca2+ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) (Banding+SERCA), parvalbumin (Banding+Parv) or ?-galactosidase (Banding+?gal), or an adeno-associated virus carrying SERCA2a (Banding+AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. “Banding”, “Banding+?gal” and “Banding+saline” groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) and slower LV relaxation rate, compared with “Normal” and “Sham”. However, “Banding+SERCA” and “Banding+Parv” showed high ESP0.1, low EDP0.1, and fast LV relaxation rate. In “Banding”, “Banding+?gal” and “Banding+saline”, slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O2 cost of total mechanical energy, was twice higher than normal value, whereas slope in “Baning+SERCA” and “Banding+Parv” was similar to normal value. Furthermore, O2 cost of LV contractility in the 3 control banding groups was ?3 times higher than normal value, whereas O2 cost of contractility in “Banding+SERCA”, “Banding+AAV.SERCA” and “Banding+Parv” was as low as normal value. Thus, high O2 osts of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.

Sakata, Susumu; Lebeche, Djamel; Sakata, Naoya; Sakata, Yuri; Chemaly, Elie R.; Liang, Li Fan; Tsuji, Tsuyoshi; Takewa, Yoshiaki; del Monte, Federica; Peluso, Richard; Zsebo, Krisztina; Jeong, Dongtak; Park, Woo Jin; Kawase, Yoshiaki; Hajjar, Roger J.

2007-01-01

268

A novel function of RNAs arising from the long terminal repeat of human endogenous retrovirus 9 in cell cycle arrest.  

PubMed

The human genome contains approximately 50 copies of the replication-defective human endogenous retrovirus 9 (ERV-9) and thousands of copies of its solitary long term repeat (sLTR) element. While some sLTRs are located upstream of critical genes and have enhancer activity, other sLTRs are located within introns and may be transcribed as RNAs. We found that intronic RNAs arising from U3 sLTRs of ERV-9 were expressed as both sense (S) and antisense (AS) transcripts in all human cells tested but that expression levels differed in malignant versus nonmalignant cells. In nonmalignant cells, AS was expressed at higher levels than S and at higher levels than in malignant cells; in malignant cells, AS was expressed at amounts equivalent to those of S RNA. Critically, U3 AS RNA was found to physically bind to key transcription factors for cellular proliferation, including NF-Y, p53, and sp1, indicating that such RNA transcripts may function as decoy targets or traps for NF-Y and thus inhibit the growth of human cancer cells. Indeed, short U3 oligodeoxynucleotides (ODNs) based on these RNA sequences ably inhibited proliferation of cancer cell lines driven by cyclins B1/B2, the gene targets of NF-Y. PMID:23097441

Xu, Lai; Elkahloun, Abdel G; Candotti, Fabio; Grajkowski, Andrzej; Beaucage, Serge L; Petricoin, Emanuel F; Calvert, Valerie; Juhl, Hartmut; Mills, Frederick; Mason, Karen; Shastri, Neal; Chik, Josh; Xu, Cynthia; Rosenberg, Amy S

2013-01-01

269

Cloning of the amphibolic Calvin cycle\\/OPPP enzyme d-ribulose-5-phosphate 3-epimerase (EC 5.1.3.1) from spinach chloroplasts: functional and evolutionary aspects  

Microsoft Academic Search

Exploiting the differential expression of genes for Calvin cycle enzymes in bundle-sheath and mesophyll cells of the C4 plant Sorghum bicolor L., we isolated via subtractive hybridization a molecular probe for the Calvin cycle enzyme d-ribulose-5-phosphate 3-epimerase (R5P3E) (EC 5.1.3.1), with the help of which several full-size cDNAs were isolated from spinach. Functional identity of the encoded mature subunit was

Ulrich Nowitzki; Ralf Wyrich; Peter Westhoff; Katrin Henze; Claus Schnarrenberger; William Martin

1995-01-01

270

Characterization of tomato Cycling Dof Factors reveals conserved and new functions in the control of flowering time and abiotic stress responses.  

PubMed

DNA binding with One Finger (DOF) transcription factors are involved in multiple aspects of plant growth and development but their precise roles in abiotic stress tolerance are largely unknown. Here we report a group of five tomato DOF genes, homologous to Arabidopsis Cycling DOF Factors (CDFs), that function as transcriptional regulators involved in responses to drought and salt stress and flowering-time control in a gene-specific manner. SlCDF1-5 are nuclear proteins that display specific binding with different affinities to canonical DNA target sequences and present diverse transcriptional activation capacities in vivo. SlCDF1-5 genes exhibited distinct diurnal expression patterns and were differentially induced in response to osmotic, salt, heat, and low-temperature stresses. Arabidopsis plants overexpressing SlCDF1 or SlCDF3 showed increased drought and salt tolerance. In addition, the expression of various stress-responsive genes, such as COR15, RD29A, and RD10, were differentially activated in the overexpressing lines. Interestingly, overexpression in Arabidopsis of SlCDF3 but not SlCDF1 promotes late flowering through modulation of the expression of flowering control genes such as CO and FT. Overall, our data connect SlCDFs to undescribed functions related to abiotic stress tolerance and flowering time through the regulation of specific target genes and an increase in particular metabolites. PMID:24399177

Corrales, Alba-Rocío; Nebauer, Sergio G; Carrillo, Laura; Fernández-Nohales, Pedro; Marqués, Jorge; Renau-Morata, Begoña; Granell, Antonio; Pollmann, Stephan; Vicente-Carbajosa, Jesús; Molina, Rosa-Victoria; Medina, Joaquín

2014-03-01

271

Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes  

PubMed Central

Proline metabolism in mammals involves two other amino acids, glutamate and ornithine, and five enzymatic activities, ?1-pyrroline-5-carboxylate (P5C) reductase (P5CR), proline oxidase, P5C dehydrogenase, P5C synthase and ornithine-?-aminotransferase (OAT). With the exception of OAT, which catalyzes a reversible reaction, the other 4 enzymes are unidirectional, suggesting that proline metabolism is purpose-driven, tightly regulated, and compartmentalized. In addition, this tri-amino-acid system also links with three other pivotal metabolic systems, namely the TCA cycle, urea cycle, and pentose phosphate pathway. Abnormalities in proline metabolism are relevant in several diseases: six monogenic inborn errors involving metabolism and/or transport of proline and its immediate metabolites have been described. Recent advances in the Human Genome Project, in silico database mining techniques, and research in dissecting the molecular basis of proline metabolism prompted us to utilize functional genomic approaches to analyze human genes which encode proline metabolic enzymes in the context of gene structure, regulation of gene expression, mRNA variants, protein isoforms, and single nucleotide polymorphisms.

Williams, D. Bart; Zhaorigetu, Siqin; Khalil, Shadi; Wan, Guanghua; Valle, David

2009-01-01

272

Metaproteomics Provides Functional Insight into Activated Sludge Wastewater Treatment  

PubMed Central

Background Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR). Methodology/Principal Findings A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism “Candidatus Accumulibacter phosphatis”. When EBPR failed, the sludge was dominated by tetrad-forming ?-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from “Candidatus Accumulibacter phosphatis” and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid ? oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. Conclusions/Significance Importantly, this study provides direct evidence linking the metabolic activities of “Accumulibacter” to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models.

Wilmes, Paul; Wexler, Margaret; Bond, Philip L.

2008-01-01

273

Linking N2O emissions from biochar-amended soil to the structure and function of the N-cycling microbial community.  

PubMed

Nitrous oxide (N2O) contributes 8% to global greenhouse gas emissions. Agricultural sources represent about 60% of anthropogenic N2O emissions. Most agricultural N2O emissions are due to increased fertilizer application. A considerable fraction of nitrogen fertilizers are converted to N2O by microbiological processes (that is, nitrification and denitrification). Soil amended with biochar (charcoal created by pyrolysis of biomass) has been demonstrated to increase crop yield, improve soil quality and affect greenhouse gas emissions, for example, reduce N2O emissions. Despite several studies on variations in the general microbial community structure due to soil biochar amendment, hitherto the specific role of the nitrogen cycling microbial community in mitigating soil N2O emissions has not been subject of systematic investigation. We performed a microcosm study with a water-saturated soil amended with different amounts (0%, 2% and 10% (w/w)) of high-temperature biochar. By quantifying the abundance and activity of functional marker genes of microbial nitrogen fixation (nifH), nitrification (amoA) and denitrification (nirK, nirS and nosZ) using quantitative PCR we found that biochar addition enhanced microbial nitrous oxide reduction and increased the abundance of microorganisms capable of N2-fixation. Soil biochar amendment increased the relative gene and transcript copy numbers of the nosZ-encoded bacterial N2O reductase, suggesting a mechanistic link to the observed reduction in N2O emissions. Our findings contribute to a better understanding of the impact of biochar on the nitrogen cycling microbial community and the consequences of soil biochar amendment for microbial nitrogen transformation processes and N2O emissions from soil. PMID:24067258

Harter, Johannes; Krause, Hans-Martin; Schuettler, Stefanie; Ruser, Reiner; Fromme, Markus; Scholten, Thomas; Kappler, Andreas; Behrens, Sebastian

2014-03-01

274

Linking N2O emissions from biochar-amended soil to the structure and function of the N-cycling microbial community  

NASA Astrophysics Data System (ADS)

Nitrous oxide (N2O) contributes 8% to global greenhouse gas emissions. Agricultural sources represent about 60% of anthropogenic N2O emissions. Most agricultural N2O emissions are due to increased fertilizer application. A considerable fraction of nitrogen fertilizers are converted to N2O by microbially-mediated processes. Soil amended with biochar has been demonstrated to reduce N2O emissions in the field and in laboratory experiments. Although N2O emission mitigation following soil biochar amendment has been reported frequently the underlying processes and specific role of the nitrogen cycling microbial community in decreasing soil N2O emissions has not been subject of systematic investigation. To investigate the impact of biochar on the microbial community of nitrogen-transforming microorganisms we performed a microcosm study with arable soil amended with different amounts (0%, 2% and 10% (w/w)) of high-temperature wood derived biochar. By quantifying the abundance and activity of functional marker genes of microbial nitrogen fixation (nifH), nitrification (amoA) and denitrification (nirK, nirS and nosZ) using quantitative real-time PCR we found that biochar addition enhanced microbial nitrous oxide reduction and increased the abundance of microorganisms capable of N2-fixation. Soil biochar amendment increased the relative gene and transcript copy numbers of the nosZ-encoded bacterial N2O reductase, suggesting a mechanistic link to the observed reduction in N2O emissions. Our findings contribute to a better understanding of the impact of biochar on the nitrogen cycling microbial community and the consequences of soil biochar amendment for microbial nitrogen transformation processes and N2O emissions from soil.

Harter, Johannes; Krause, Hans-Martin; Schuettler, Stefanie; Ruser, Reiner; Fromme, Markus; Scholten, Thomas; Kappler, Andreas; Behrens, Sebastian

2014-05-01

275

In vitro mimicking of estrous cycle stages in porcine oviduct epithelium cells: estradiol and progesterone regulate differentiation, gene expression, and cellular function.  

PubMed

Throughout the estrous cycle the oviduct epithelium undergoes dramatic morphological and functional changes. To elucidate cyclic cellular events and associated regulation mechanisms of 17beta estradiol (E2) and progesterone (P4), we mimicked estrous cycle stages in vitro using a culture system of primary porcine oviduct epithelium cells (POEC). Cells were polarized in an air/liquid interface and then treated with E2 and P4 for physiological time periods: In experiment 1, high concentration of P4 with low concentration of E2 for 10 days resembled diestrus; in experiment 2, following the previous diestrus, sequential high E2 with low P4 for 2.5 days represented estrus. Histomorphometry and electron microscopy showed cyclic changes in cellular height, cell population, and cilia density under the influence of hormone stimulation. Transepithelial electrical resistance was high in simulated diestrus but reduced in estrus. Thus, E2 and P4 affect cellular polarity, transformation of ciliated and secretory cells, as well as electrical conductivity of oviduct epithelium. Simulation of diestrus led to significant decrease in expression of hormone receptors (PGR and ESR1) and other epithelial markers (MUC16, OVGP1, and HSP90B1), while sequential simulated estrus caused an increase in these markers. The hormonal regulation of some marker genes was clearly time-dependent. Furthermore, POEC showed increased sperm-binding capacity in simulated estrus. In this study, we also present a novel approach based on the AndroVision software, which can be routinely utilized as a parameter for ciliary activity, and for the first time, we showed fluid movement patterns along the epithelium lining in vitro. PMID:23904510

Chen, Shuai; Einspanier, Ralf; Schoen, Jennifer

2013-09-01

276

Effect of post-exercise protein-leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling.  

PubMed

Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h(-1), respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h(-1)) beverages for 1-3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 (-)) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15-17 mmol O2 (-) cell(-1) ± 90 % confidence limits 20 mmol O2 (-) cell(-1)). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 (-) (33 ± 20 mmol O2 (-) cell(-1)), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein-leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on day 6, which could impact neutrophil-dependent processes during recovery from intense training. PMID:23624785

Nelson, Andre R; Jackson, Lara; Clarke, Jim; Stellingwerff, Trent; Broadbent, Suzanne; Rowlands, David S

2013-09-01

277

In silico assessment of the metabolic capabilities of an engineered functional reversal of the ?-oxidation cycle for the synthesis of longer-chain (C?4) products.  

PubMed

The modularity and versatility of an engineered functional reversal of the ?-oxidation cycle make it a promising platform for the synthesis of longer-chain (C?4) products. While the pathway has recently been exploited for the production of n-alcohols and carboxylic acids, fully capitalizing on its potential for the synthesis of a diverse set of product families requires a system-level assessment of its biosynthetic capabilities. To this end, we utilized a genome scale model of Escherichia coli, in combination with Flux Balance Analysis and Flux Variability Analysis, to determine the key characteristics and constraints of this pathway for the production of a variety of product families under fermentative conditions. This analysis revealed that the production of n-alcohols, alkanes, and fatty acids of lengths C3-C18 could be coupled to cell growth in a strain lacking native fermentative pathways, a characteristic enabling product synthesis at maximum rates, titers, and yields. While energetic and redox constraints limit the production of target compounds from alternative platforms such as the fatty acid biosynthesis and ?-ketoacid pathways, the metabolic efficiency of a ?-oxidation reversal allows the production of a wide range of products of varying length and functionality. The versatility of this platform was investigated through the simulation of various termination pathways for product synthesis along with the use of different priming molecules, demonstrating its potential for the efficient synthesis of a wide variety of functionalized compounds. Overall, specific metabolic manipulations suggested by this systems-level analysis include deletion of native fermentation pathways, the choice of priming molecules and specific routes for their synthesis, proper choice of termination enzymes, control of flux partitioning at the pyruvate node and the pentose phosphate pathway, and the use of an NADH-dependent trans-enoyl-CoA reductase instead of a ferredoxin-dependent enzyme. PMID:24569100

Cintolesi, Angela; Clomburg, James M; Gonzalez, Ramon

2014-05-01

278

TRIIODOTHYRONINE INCREASES MYOCARDIAL FUNCTION AND PYRUVATE ENTRY INTO THE CITRIC ACID CYCLE AFTER REPERFUSION IN A MODEL OF INFANT CARDIOPULMONARY BYPASS  

SciTech Connect

We utilized a translational model of infant CPB to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC) thereby providing the energy support for improved cardiac function after ischemia-reperfusion. Methods and Results: Neonatal piglets received intracoronary [2-13Carbon(13C)]-pyruvate for 40 minutes (8 mM) during control aerobic conditions (Cont) or immediately after reperfusion (IR) from global hypothermic ischemia. A third group (IR-Tr) received T3 (1.2 ug/kg) during reperfusion. We assessed absolute CAC intermediate levels (aCAC) and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC ) and anaplerotic carboxylation (PC; ) using 13C-labeled pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C NMR. Neither IR nor IR-Tr modified aCAC. However, compared to IR, T3 (group IR-Tr) increased cardiac power and oxygen consumption after CPB while elevating both PDC and PC (~ four-fold). T3 inhibited IR induced reductions in CAC intermediate molar percent enrichment (MPE) and oxaloacetate(citrate)/malate MPE ratio; an index of aspartate entry into the CAC. Conclusions: T3 markedly enhances PC and PDC thereby providing substrate for elevated cardiac function and work after reperfusion. The increases in pyruvate flux occur with preservation of the CAC intermediate pool. Additionally, T3 inhibition of reductions in CAC intermediate MPEs indicates that T3 reduces the reliance on amino acids (AA) for anaplerosis after reperfusion. Thus, AA should be more available for other functions such as protein synthesis.

Olson, Aaron; Bouchard, Bertrand; Ning, Xue-Han; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

2012-03-01

279

Physiological pineal effects on female reproductive function of laboratory rats: prenatal development of pups, litter size and estrous cycle in middle age.  

PubMed

The present study investigates whether and how the pineal or its hormone melatonin influences female reproductive functions, namely the litter size, prenatal development of offsprings, and estrous cyclicity, especially its age-related cessation in a non-seasonal breeder, the laboratory rat. Wistar rats were maintained under a 24 h light-dark (12Lratio12D) cycle. Female rats were divided into 3 groups: non-operated (NO), sham-operated (SX), and pinealectomized (PX). Surgeries were performed in 35-40 day-old females. Starting at an age between 70 days and 7 months, female rats of all 3 groups were repeatedly mated with intact males. PX mothers more frequently delivered pups with malformations (e.g., taillessness, hydronephrosis, 7 out of 1263 pups) than control rats (0/1323; p<0.007). In the first delivery at 3 months of age, but not at later ages, PX mothers delivered more pups of lower body weight than control animals (p<0.001). Examination of vaginal smears showed that almost all female rats of the NO, SX, and PX groups had 4-day estrous cyclicity when they were young-between 60 days and 5 months of age. At an age of 17 to 18 months, most female rats of the NO and SX groups showed irregular, continuously diestrous or pseudopregnancy-like patterns, and 4-day estrous cyclicity was found in only 10% of the NO or SX animals. In contrast, about 50% of the PX rats showed 4-day estrous cyclicity at this older age (p< 0.001). Melatonin, when added to drinking water (0.4 mg/L) for 16 days during the dark phase increased the frequency of diestrous phase, except in continuously diestrous rats and very few others. This melatonin effect was strong in PX rats but relatively weak in SX rats. In conclusion, the pineal hormone appears to influence various reproductive functions and developmental processes, especially pregnancy and the timing of reproductive aging in rats. The effects of pinealectomy are more prominent at an age of 60 to 80 days (i.e., shortly after puberty) and at the beginning of the cessation of cycles in middle-aged females. PMID:16687302

Kachi, Takashi; Tanaka, Dai; Watanabe, Seiji; Suzuki, Reiko; Tonosaki, Yoshikazu; Fujieda, Hiroki

2006-01-01

280

Water Cycle  

NSDL National Science Digital Library

Students will use this short interactive activity to check their understanding on what they learned about the water cycle Do you drink the same water as your great grandparents did? Check this website then answer the following questions. COLLECTION 1. How many times does water go through the cycle? 2. Explain each part of the cycle and why it is important. 3. Construct a model or diagram based off the information from this ...

Peterson, Lori

2009-09-28

281

carbon cycle  

NSDL National Science Digital Library

Life on earth is based on carbon. Living things acquire carbon from their environment - from air, water, soil, and rock and from other living things - through processes such as photosynthesis, respiration and decomposition. The carbon cycle model is a representation of the movement of carbon from sources to sinks through chemical and physical transfers. The carbon cycle activity allows students to see the effect of fossil fuel burning on the carbon cycle.

School, Maryland V.

282

Functional genomic analysis of commercial baker's yeast during initial stages of model dough-fermentation  

Microsoft Academic Search

Gene expression profiles of baker's yeast during initial dough-fermentation were investigated using liquid fermentation (LF) media to obtain insights at the molecular level into rapid adaptation mechanisms of baker's yeast. Results showed that onset of fermentation caused drastic changes in gene expression profiles within 15min. Genes involved in the tricarboxylic acid (TCA) cycle were down-regulated and genes involved in glycolysis

Fumiko Tanaka; Akira Ando; Toshihide Nakamura; Hiroshi Takagi; Jun Shima

2006-01-01

283

A Conserved Cyclin-Binding Domain Determines Functional Interplay between Anaphase-Promoting Complex-Cdh1 and Cyclin A-Cdk2 during Cell Cycle Progression  

Microsoft Academic Search

Periodic activity of the anaphase-promoting complex (APC) ubiquitin ligase determines progression through multiple cell cycle transitions by targeting cell cycle regulators for destruction. At the G1\\/S transition, phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits the APC, allowing stabiliza- tion of proteins required for subsequent cell cycle progression. Cyclin-dependent kinases (CDKs) that initiate and maintain Cdh1 phosphorylation have been identified. However,

C. S. Sorensen; CLAUDIA LUKAS; EDGAR R. KRAMER; JAN-MICHAEL PETERS; JIRI BARTEK; JIRI LUKAS

2001-01-01

284

function  

Microsoft Academic Search

Integral equations for the spin-weighted spheroidal wave functions is given . For the prolate spheroidal wave function with m = 0, there exists the integral equation whose kernel is sin x x , and the sinc function kernel sin x x is of great mathematical significance. In the paper, we also extend the similar sinc function kernel sin x x

Guihua Tian

285

The Association of Cell Cycle Checkpoint 2 Variants and Kidney Function: Findings of the Family Blood Pressure Program and the Atherosclerosis Risk in Communities Study  

PubMed Central

BACKGROUND Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease. METHODS We used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. We performed replication analyses in the Genetic Epidemiology Network of Arteriopathy (GENOA) participants (1,746 African Americans and 1,418 whites), GenNet participants (706 whites), and Atherosclerosis Risk in Communities (ARIC) study participants (3,783 African Americans and 10,936 whites). All analyses were race-stratified and used additive genetic models with adjustments for covariates and for family structure, if needed. RESULTS One tag-SNP, rs5762764, was associated with eGFR in HyperGEN P = (0.003) and GENOA white participants (P = 0.009), and it was significantly associated with eGFR in meta-analyses (P = 0.002). The associations were independent of type 2 diabetes. CONCLUSIONS These results suggest that CHEK2 variants may influence eGFR in the context of hypertension.

Franceschini, Nora; North, Kari E.; Arnett, Donna; Pankow, James S.; Chung, Jay H.; Baird, Lisa; Leppert, Mark F.; Eckfeldt, John H.; Boerwinkle, Eric; Gu, C. Charles; Lewis, Cora E.; Myers, Richard H.; Turner, Stephen T.; Weder, Alan; Kao, W.H. Linda; Mosley, Thomas H.; Chakravarti, Aravinda; Kramer, Holly; Zhang, Jinghui; Hunt, Steven C.

2009-01-01

286

Role for a region of helically unstable DNA within the Epstein-Barr virus latent cycle origin of DNA replication oriP in origin function  

SciTech Connect

The minimal replicator of the Epstein-Barr virus (EBV) latent cycle origin of DNA replication oriP is composed of two binding sites for the Epstein-Barr virus nuclear antigen-1 (EBNA-1) and flanking inverted repeats that bind the telomere repeat binding factor TRF2. Although not required for minimal replicator activity, additional binding sites for EBNA-1 and TRF2 and one or more auxiliary elements located to the right of the EBNA-1/TRF2 sites are required for the efficient replication of oriP plasmids. Another region of oriP that is predicted to be destabilized by DNA supercoiling is shown here to be an important functional component of oriP. The ability of DNA fragments of unrelated sequence and possessing supercoiled-induced DNA duplex destabilized (SIDD) structures, but not fragments characterized by helically stable DNA, to substitute for this component of oriP demonstrates a role for the SIDD region in the initiation of oriP-plasmid DNA replication.

Polonskaya, Zhanna [Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794 (United States); Benham, Craig J. [Department of Mathematics, University of California at Davis, Davis, CA 95616 (United States); Hearing, Janet [Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794 (United States)]. E-mail: jhearing@ms.cc.sunysb.edu

2004-10-25

287

Complementation of the Function of Glycoprotein H of Human Herpesvirus 6 Variant A by Glycoprotein H of Variant B in the Virus Life Cycle  

PubMed Central

Human herpesvirus 6 (HHV-6) is a T-cell-tropic betaherpesvirus. HHV-6 can be classified into two variants, HHV-6 variant A (HHV-6A) and HHV-6B, based on genetic, antigenic, and cell tropisms, although the homology of their entire genomic sequences is nearly 90%. The HHV-6A glycoprotein complex gH/gL/gQ1/gQ2 is a viral ligand that binds to the cellular receptor human CD46. Because gH has 94.3% amino acid identity between the variants, here we examined whether gH from one variant could complement its loss in the other. Recently, we successfully reconstituted HHV-6A from its cloned genome in a bacterial artificial chromosome (BAC) (rHHV-6ABAC). Using this system, we constructed HHV-6ABAC DNA containing the HHV-6B gH (BgH) gene instead of the HHV-6A gH (AgH) gene in Escherichia coli. Recombinant HHV-6ABAC expressing BgH (rHHV-6ABAC-BgH) was successfully reconstituted. In addition, a monoclonal antibody that blocks HHV-6B but not HHV-6A infection neutralized rHHV-6ABAC-BgH but not rHHV-6ABAC. These results indicate that HHV-6B gH can complement the function of HHV-6A gH in the viral infectious cycle.

Oyaizu, Hiroko; Tang, Huamin; Ota, Megumi; Takenaka, Nobuyuki; Ozono, Keiichi; Yamanishi, Koichi

2012-01-01

288

Triiodothyronine increases myocardial function and pyruvate entry into the citric acid cycle after reperfusion in a model of infant cardiopulmonary bypass.  

PubMed

Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC), thereby providing the energy support for improved cardiac function after ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-(13)Carbon((13)C)]pyruvate for 40 min (8 mM) during control aerobic conditions (control) or immediately after reperfusion (I/R) from global hypothermic ischemia. A third group (I/R-Tr) received T3 (1.2 ?g/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-(13)C]pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and (13)C-nuclear magnetic resonance spectroscopy. When compared with I/R, T3 (group I/R-Tr) increased cardiac power and oxygen consumption after I/R while elevating flux of both PDC and PC (?4-fold). Although neither I/R nor I/R-Tr modified absolute CAC levels, T3 inhibited I/R-induced reductions in their molar percent enrichment. Furthermore, (13)C-labeling of CAC intermediates suggests that T3 may decrease entry of unlabeled carbons at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. T3 markedly enhances PC and PDC fluxes, thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occurs with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion. PMID:22180654

Olson, Aaron K; Bouchard, Bertrand; Ning, Xue-Han; Isern, Nancy; Rosiers, Christine Des; Portman, Michael A

2012-03-01

289

Effect of In Situ Thermal Cycle Annealing on GaN Film Properties Grown on (001) and (111) GaAs, and Sapphire Substrates  

NASA Astrophysics Data System (ADS)

The effect of in-situ thermal cycle annealing (TCA) has been investigated for GaN growth on GaAs(lOO), GaAs(111) and sapphire substrates. X-ray diffractometry (XRD) and surface morphology studies were performed for this purpose. Enhanced cubic phase characteristics were observed by employing annealingfor GaN layers grown on (001) GaAs. The thickness of the layer subject to annealing is critical in determining the phase of the subsequently grown layer. Thin initial layers appear to permit maintenance of the cubic phase characteristics shown by the substrate, while hexagonal phase characteristics are manifested for thick initial layers. Higher temperature of annealing of thick pre-annealed layers results in changes from mixed cubic/hexagonal phase to pure hexagonal phase. Growth on GaAs(111) substrates showed single cubic phase characteristics and similar enhancement of crystal quality by using TCA as for layers on GaAs(OOl). Micro-cracks were found to be present after TCA on GaAs(lll) substrates. Thermal cycling also appears to be beneficial for layers grown on sapphire substrates.

Wang, Kun; Pavlidis, Dimitris; Cao, Jun

1997-12-01

290

Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells  

PubMed Central

Glutamine metabolism is crucial for cancer cell growth via the generation of intermediate molecules in the tricarboxylic acid (TCA) cycle, antioxidants and ammonia. The goal of the current study was to evaluate the effects of glutamine on metabolism in the breast cancer tumor microenvironment, with a focus on autophagy and cell death in both epithelial and stromal compartments. For this purpose, MCF7 breast cancer cells were cultured alone or co-cultured with nontransformed fibroblasts in media containing high glutamine and low glucose (glutamine +) or under control conditions, with no glutamine and high glucose (glutamine ?). Here, we show that MCF7 cells maintained in co-culture with glutamine display increased mitochondrial mass, as compared with control conditions. Importantly, treatment with the autophagy inhibitor chloroquine abolishes the glutamine-induced augmentation of mitochondrial mass. It is known that loss of caveolin-1 (Cav-1) expression in fibroblasts is associated with increased autophagy and an aggressive tumor microenvironment. Here, we show that Cav-1 downregulation which occurs in fibroblasts maintained in co-culture specifically requires glutamine. Interestingly, glutamine increases the expression of autophagy markers in fibroblasts, but decreases expression of autophagy markers in MCF7 cells, indicating that glutamine regulates the autophagy program in a compartment-specific manner. Functionally, glutamine protects MCF7 cells against apoptosis, via the upregulation of the anti-apoptotic and anti-autophagic protein TIGAR. Also, we show that glutamine cooperates with stromal fibroblasts to confer tamoxifen-resistance in MCF7 cancer cells. Finally, we provide evidence that co-culture with fibroblasts (1) promotes glutamine catabolism, and (2) decreases glutamine synthesis in MCF7 cancer cells. Taken together, our findings suggest that autophagic fibroblasts may serve as a key source of energy-rich glutamine to fuel cancer cell mitochondrial activity, driving a vicious cycle of catabolism in the tumor stroma and anabolic tumor cell expansion.

Ko, Ying-Hui; Lin, Zhao; Flomenberg, Neal; Pestell, Richard G; Howell, Anthony; Sotgia, Federica

2011-01-01

291

Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins.  

PubMed

Experimental models for esophageal epithelium in vitro either suffer from poor differentiation or complicated culture systems. An air-liquid interface system with normal human bronchial epithelial cells can serve as a model of esophageal-like squamous epithelial cell layers. Here, we explore the influence of bile acids on barrier function and tight junction (TJ) proteins. The cells were treated with taurocholic acid (TCA), glycocholic acid (GCA), or deoxycholic acid (DCA) at different pH values, or with pepsin. Barrier function was measured by transepithelial electrical resistance (TEER) and the diffusion of paracellular tracers (permeability). The expression of TJ proteins, including claudin-1 and claudin-4, was examined by Western blotting of 1% Nonidet P-40-soluble and -insoluble fractions. TCA and GCA dose-dependently decreased TEER and increased paracellular permeability at pH 3 after 1 h. TCA (4 mM) or GCA (4 mM) did not change TEER and permeability at pH 7.4 or pH 4. The combination of TCA and GCA at pH 3 significantly decreased TEER and increased permeability at lower concentrations (2 mM). Pepsin (4 mg/ml, pH 3) did not have any effect on barrier function. DCA significantly decreased the TEER and increased permeability at pH 6, a weakly acidic condition. TCA (4 mM) and GCA (4 mM) significantly decreased the insoluble fractions of claudin-1 and claudin-4 at pH 3. In conclusion, acidic bile salts disrupted the squamous epithelial barrier function partly by modulating the amounts of claudin-1 and claudin-4. These results provide new insights for understanding the role of TJ proteins in esophagitis. PMID:21617116

Chen, Xin; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Matsumoto, Takayuki; Miwa, Hiroto

2011-08-01

292

Determining novel functions of Arabidopsis 14-3-3 proteins in central metabolic processes  

PubMed Central

Background 14-3-3 proteins are considered master regulators of many signal transduction cascades in eukaryotes. In plants, 14-3-3 proteins have major roles as regulators of nitrogen and carbon metabolism, conclusions based on the studies of a few specific 14-3-3 targets. Results In this study, extensive novel roles of 14-3-3 proteins in plant metabolism were determined through combining the parallel analyses of metabolites and enzyme activities in 14-3-3 overexpression and knockout plants with studies of protein-protein interactions. Decreases in the levels of sugars and nitrogen-containing-compounds and in the activities of known 14-3-3-interacting-enzymes were observed in 14-3-3 overexpression plants. Plants overexpressing 14-3-3 proteins also contained decreased levels of malate and citrate, which are intermediate compounds of the tricarboxylic acid (TCA) cycle. These modifications were related to the reduced activities of isocitrate dehydrogenase and malate dehydrogenase, which are key enzymes of TCA cycle. In addition, we demonstrated that 14-3-3 proteins interacted with one isocitrate dehydrogenase and two malate dehydrogenases. There were also changes in the levels of aromatic compounds and the activities of shikimate dehydrogenase, which participates in the biosynthesis of aromatic compounds. Conclusion Taken together, our findings indicate that 14-3-3 proteins play roles as crucial tuners of multiple primary metabolic processes including TCA cycle and the shikimate pathway.

2011-01-01

293

A decay function model for the integrity loss of rock when subjected to recurrent cycles of freezing–thawing and heating–cooling  

Microsoft Academic Search

Rocks are used in engineering works as monument or building stone and as architectural covering stone. As a result, they can be subjected to recurrent cycles of freezing and thawing and will be subjected to heating and cooling. They loose some of their integrity under these cyclic temperature variations and the more frequent and severe these cycles, the higher the

M Mutlutürk; R Altindag; G Türk

2004-01-01

294

Simulation of Marine Nitrogen Cycling as Function of Atmospheric Oxygen: Results of a Coupled C,N,P,O,S Biogeochemical Model Including d15N  

NASA Astrophysics Data System (ADS)

Bioavailable nitrogen is a critical limiting nutrient in the modern marine biosphere. We expect that the rate of denitrification may have been higher in the geologic past due to decreased atmospheric O2 and expanded ocean anoxia. To examine the consequences of this idea, we present numerical simulations of coupled carbon, nitrogen, phosphorus, oxygen, and sulfur cycling as a function of atmospheric oxygen in an ocean with circulation similar to modern conditions. The model has been specifically developed to function over a wide range of ocean redox conditions and has been successfully tested in simulations of both the modern global ocean and Black Sea. Global rates of nitrogen fixation and pelagic denitrification, which are strongly coupled in our default model, reach maximum rates between 25% and 50% of the present atmospheric level of O2 (PAL O2). At 40% PAL O2, the simulated steady-state pelagic denitrification rate is 82.1 Tmol/yr, and the N- fixation rate is 85.7 Tmol/yr. These rates are 8-15× greater than modern estimates. The maximum simulated rate of N-fixation is determined by the N flux required to entirely support export production. At mid- levels of atmospheric oxygen, large areas of the oceans are characterized by a suboxic to anoxic "oxygen minimum zone" between 100m and 1000m depth which is over- and underlain by oxic water. Under these conditions, denitrification in the upper water column is nearly complete, suppressing the ?15N isotopic signal for this process. To test the impact of limitation of N-fixation (e.g. by trace metals, light, temperature) we imposed a cap on the global N-fixation rate. In these simulations, limitation of N-fixation below 50% PAL O2 results in severe N limitation of primary production and low mean oceanic N:P. Our results imply that N limitation may have been chronic at intermediate levels of atmospheric O2. At the same time, low N:P conditions would create evolutionary pressure for efficient N-fixation pathways and high N use efficiency in non-fixing marine phytoplankton, testing the limits of plasticity in the Redfield ratio. If N-fixation were unable to keep up with high rates of denitrification at intermediate levels of atmospheric O2, intense N limitation of Proterozoic marine primary production may have strongly inhibited any further rise of atmospheric O2, thus stabilizing atmospheric O2 at <25% PAL.

Romaniello, S. J.; Derry, L. A.

2008-12-01

295

Vapor Compression Cycle Design Program (CYCLE_D)  

National Institute of Standards and Technology Data Gateway

SRD 49 NIST Vapor Compression Cycle Design Program (CYCLE_D) (PC database for purchase)   The CYCLE_D database package simulates the vapor compression refrigeration cycles. It is fully compatible with REFPROP 9.0 and covers the 62 single-compound refrigerants . Fluids can be used in mixtures comprising up to five components.

296

Preferences for foods with varying levels of salt and fat differ as a function of dietary restraint and exercise but not menstrual cycle  

Microsoft Academic Search

Women commonly report increased cravings for foods high in sugar, fat, and\\/or salt premenstrually relative to other times during the menstrual cycle. To determine if elevated cravings for foods high in salt and\\/or fat were related to alterations in food preferences across the menstrual cycle, preference and sensory ratings for air-popped popcorn with varying levels of salt (0.0, 1.5, and

Robin B. Kanarek; Michelle Ryu; Jeanne Przypek

1995-01-01

297

function  

Microsoft Academic Search

The large complex zeros of the Jost function (poles of the S matrix) in the complex wave number-plane for s-wave scattering by truncated potentials are associated to the distribution of large prime numbers {pn} as well as to the asymptotic behavior of the imaginary parts {tn} of the zeros of the Riemann zeta function on the critical line. A variant

Sergio Joffily

298

Cycle Sequencing  

NSDL National Science Digital Library

This animation from Cold Spring Harbor Laboratory's Dolan DNA Learning Center presents the cycle sequencing. The animation contains instructions on how to sequence a piece of DNA beginning with the raw materials needed, and details on the process: "Fluorescent dyes are added to the reactions, and a laser within an automated DNA sequencing machine is used to analyze the DNA fragments produced."

2011-11-23

299

Menu Cycles.  

ERIC Educational Resources Information Center

The curriculum guide for commercial foods instruction is designed to aid the teacher in communicating the importance of menu cycles in commercial food production. It also provides information about the necessary steps in getting food from the raw form to the finished product, and then to the consumer. In addition to providing information on how to…

Clayton, Alfred; Almony, John

300

Cycles determination  

Microsoft Academic Search

Cycle determination, i.e. research and detection of quasi monochromatic signals, is certainly not an easy task. Indeed, there are numerous mathematical, or less mathematical, methods proposed for this purpose. However, pitfalls in applications are nearly as numerous as the proposed methods. This is due to the fact that the main procedures require mathematical properties which are not fulfilled in reality

J. De Prins; C. Bovy; G. Cornélissen; R. Gillard

1972-01-01

301

A Functional Calvin Cycle Is Not Indispensable for the Light Activation of C4 Phosphoenolpyruvate Carboxylase Kinase and Its Target Enzyme in the Maize Mutant bundle sheath defective2-mutable1  

Microsoft Academic Search

We used a pale-green maize (Zea mays L.) mutant that fails to accumulate ribulose-1,5-bisphosphate carboxylase\\/oxygenase (Rubisco) to test the working hypothesis that the regulatory phos- phorylation of C4 phosphoenolpyruvate carboxylase (PEPC) by its Ca21-insensitive protein-serine\\/threonine kinase (PEPC kinase) in the C4 mesophyll cytosol depends on cross-talk with a functional Calvin cycle in the bundle sheath. Wild-type (W22) and bundle sheath

Lucy H. Smith; Jane A. Langdale; Raymond Chollet

1998-01-01

302

Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance.  

PubMed

Glutamine metabolism is crucial for cancer cell growth via the generation of intermediate molecules in the tricarboxylic acid (TCA) cycle, antioxidants and ammonia. The goal of the current study was to evaluate the effects of glutamine on metabolism in the breast cancer tumor microenvironment, with a focus on autophagy and cell death in both epithelial and stromal compartments. For this purpose, MCF7 breast cancer cells were cultured alone or co-cultured with non-transformed fibroblasts in media containing high glutamine and low glucose (glutamine +) or under control conditions, with no glutamine and high glucose (glutamine -). Here, we show that MCF7 cells maintained in co-culture with glutamine display increased mitochondrial mass, as compared with control conditions. Importantly, treatment with the autophagy inhibitor chloroquine abolishes the glutamine-induced augmentation of mitochondrial mass. It is known that loss of caveolin-1 (Cav-1) expression in fibroblasts is associated with increased autophagy and an aggressive tumor microenvironment. Here, we show that Cav-1 downregulation which occurs in fibroblasts maintained in co-culture specifically requires glutamine. Interestingly, glutamine increases the expression of autophagy markers in fibroblasts, but decreases expression of autophagy markers in MCF7 cells, indicating that glutamine regulates the autophagy program in a compartment-specific manner. Functionally, glutamine protects MCF7 cells against apoptosis, via the upregulation of the anti-apoptotic and anti-autophagic protein TIGAR. Also, we show that glutamine cooperates with stromal fibroblasts to confer tamoxifen-resistance in MCF7 cancer cells. Finally, we provide evidence that co-culture with fibroblasts (1) promotes glutamine catabolism, and (2) decreases glutamine synthesis in MCF7 cancer cells. Taken together, our findings suggest that autophagic fibroblasts may serve as a key source of energy-rich glutamine to fuel cancer cell mitochondrial activity, driving a vicious cycle of catabolism in the tumor stroma and anabolic tumor cell expansion. PMID:22236876

Ko, Ying-Hui; Lin, Zhao; Flomenberg, Neal; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

2011-12-15

303

The Life Cycle of Centrioles  

PubMed Central

Centrioles organize the centrosome and nucleate the ciliary axoneme, and the centriole life cycle has many parallels to the chromosome cycle. The centriole cycle in animals begins at fertilization with the contribution of two centrioles by the male gamete. In the ensuing cell cycles, the duplication of centrioles is controlled temporally, spatially, and numerically. As a consequence of the duplication mechanism, the two centrioles in a typical interphase cell are of different ages and have different functions. Here, we discuss how new centrioles are assembled, what mechanisms limit centriole number, and the consequences of the inherent asymmetry of centriole duplication and segregation.

Hatch, E.

2013-01-01

304

Technology Life Cycle.  

National Technical Information Service (NTIS)

OUTLINE: DoD Life Cycle - NASA Life Cycle - Generic Life Cycle - Technology Readiness Levels - Exceptions - Product Life Cycle - Product and Technology Life Cycles Together. CONCLUSION: Technology Maturity Measures Where You are in the Technology Life Cyc...

B. Nolte

2006-01-01

305

Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum  

PubMed Central

Background The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved. Results We reassessed the central carbon metabolism of P. falciparum asexual and sexual blood stages, by metabolically labeling each stage with 13C-glucose and 13C-glutamine, and analyzing isotopic enrichment in key pathways using mass spectrometry. In contrast to previous findings, we found that carbon skeletons derived from both glucose and glutamine are catabolized in a canonical oxidative TCA cycle in both the asexual and sexual blood stages. Flux of glucose carbon skeletons into the TCA cycle is low in the asexual blood stages, with glutamine providing most of the carbon skeletons, but increases dramatically in the gametocyte stages. Increased glucose catabolism in the gametocyte TCA cycle was associated with increased glucose uptake, suggesting that the energy requirements of this stage are high. Significantly, whereas chemical inhibition of the TCA cycle had little effect on the growth or viability of asexual stages, inhibition of the gametocyte TCA cycle led to arrested development and death. Conclusions Our metabolomics approach has allowed us to revise current models of P. falciparum carbon metabolism. In particular, we found that both asexual and sexual blood stages utilize a conventional TCA cycle to catabolize glucose and glutamine. Gametocyte differentiation is associated with a programmed remodeling of central carbon metabolism that may be required for parasite survival either before or after uptake by the mosquito vector. The increased sensitivity of gametocyte stages to TCA-cycle inhibitors provides a potential target for transmission-blocking drugs.

2013-01-01

306

Carbon Cycle  

NSDL National Science Digital Library

Elementary students often successfully memorize and repeat back the stages in cycles, with no deep conceptual understanding of the complexities of the processes involved. Their ability to synthesize knowledge of the cycles with a wider breadth of information related to real-world, unresolved environmental issues such as global warming, greenhouse gas emissions or the burning of biomass for fuel is probably less well developed. In order to engage in meaningful discussions of carbon-related environmental issues, students also need an understanding of the changing nature of the earth s atmosphere. The relative proportion of nitrogen, carbon dioxide, oxygen, ozone and other gases is neither consistent around the world nor constant over time. What factors contribute to the variability in atmospheric content? Which of the factors should be controlled? What are the possible approaches to controlling them? What are the possible and probable outcomes of such controlling measures?

Lefever, Mary

2007-01-01

307

Rock Cycle  

NSDL National Science Digital Library

Through five lessons, students are introduced to all facets of the rock cycle. Topics include rock and mineral types, material stresses and weathering, geologic time and fossil formation, the Earth's crust and tectonic plates, and soil formation and composition. Lessons are presented in the context of the related impact on humans in the form of roadway and tunnel design and construction, natural disasters, environmental site assessment for building structures, and measurement instrumentation and tools. Hands-on activities include experiencing tensional, compressional and shear material stress by using only hand force to break bars of soap; preparing Jeopardy-type trivia questions/answers for a class game that reinforces students' understanding of rocks and the rock cycle; creating "fossils" using melted chocolate; working within design constraints to design and build a model tunnel through a clay mountain; and soil sampling by creating tools, obtaining soil cores, documenting a soil profile log, and analyzing the findings to make engineering predictions.

Integrated Teaching And Learning Program

308

Limit cycles in four dimensions  

NASA Astrophysics Data System (ADS)

We present an example of a limit cycle, i.e., a recurrent flow-line of the beta-function vector field, in a unitary four-dimensional gauge theory. We thus prove that beta functions of four-dimensional gauge theories do not produce gradient flows. The limit cycle is established in perturbation theory with a three-loop calculation which we describe in detail.

Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

2012-12-01

309

FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate.  

PubMed

Pyruvate dehydrogenase kinase (PDK) is activated in right ventricular hypertrophy (RVH), causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. The stimulus for PDK upregulation, its isoform specificity, and the long-term effects of PDK inhibition are unknown. We hypothesize that FOXO1-mediated PDK4 upregulation causes bioenergetic impairment and RV dysfunction, which can be reversed by dichloroacetate. Adult male Fawn-Hooded rats (FHR) with pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH; age 6-12 months) were compared to age-matched controls. Glucose oxidation (GO) and fatty acid oxidation (FAO) were measured at baseline and after acute dichloroacetate (1 mM × 40 min) in isolated working hearts and in freshly dispersed RV myocytes. The effects of chronic dichloroacetate (0.75 g/L drinking water for 6 months) on cardiac output (CO) and exercise capacity were measured in vivo. Expression of PDK4 and its regulatory transcription factor, FOXO1, were also measured in FHR and RV specimens from PAH patients (n = 10). Microarray analysis of 168 genes related to glucose or FA metabolism showed >4-fold upregulation of PDK4, aldolase B, and acyl-coenzyme A oxidase. FOXO1 was increased in FHR RV, whereas HIF-1 ? was unaltered. PDK4 expression was increased, and the inactivated form of FOXO1 decreased in human PAH RV (P < 0.01). Pyruvate dehydrogenase (PDH) inhibition in RVH increased proton production and reduced GO's contribution to the tricarboxylic acid (TCA) cycle. Acutely, dichloroacetate reduced RV proton production and increased GO's contribution (relative to FAO) to the TCA cycle and ATP production in FHR (P < 0.01). Chronically dichloroacetate decreased PDK4 and FOXO1, thereby activating PDH and increasing GO in FHR. These metabolic changes increased CO (84 ± 14 vs. 69 ± 14 ml/min, P < 0.05) and treadmill-walking distance (239 ± 20 vs. 171 ± 22 m, P < 0.05). Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores GO, leading to improved bioenergetics and RV function in RVH. PMID:23247844

Piao, Lin; Sidhu, Vaninder K; Fang, Yong-Hu; Ryan, John J; Parikh, Kishan S; Hong, Zhigang; Toth, Peter T; Morrow, Erik; Kutty, Shelby; Lopaschuk, Gary D; Archer, Stephen L

2013-03-01

310

Metabolite and isotopomer balancing in the analysis of metabolic cycles. 1: Theory  

SciTech Connect

Proper analysis of label distribution in metabolic pathway intermediates is critical for correct interpretation of experimental data and strategic experimental design. While, for example, {sup 13}C nuclear magnetic resonance (NMR) spectroscopy is usually limited to the measurement of degrees of {sup 13}C enrichment, more information about metabolic fluxes can be extracted from the fine structure of NMR spectra, or molecular weight distributions of isotopomers of metabolic intermediates (measured by gas chromatography-mass spectrometry). For this purpose, rigorous accounting for the contribution of all pathways to label distribution is required, especially contributions resulting from multiple turns of metabolic cycles. In this paper the authors present a mathematical model developed to analyze isotopomer distributions of tricarboxylic acid cycle (TCA) intermediates following the administration of {sup 13}C (or {sup 14}C) labeled substrates. The theory presented provides the basis to analyze {sup 13}C NMR spectra and molecular weight distributions of metabolites.

Klapa, M.I.; Park, S.M.; Sinskey, A.J.; Stephanopoulos, G. [Massachusetts Inst. of Tech., Cambridge, MA (United States)] [Massachusetts Inst. of Tech., Cambridge, MA (United States)

1999-02-20

311

Evidence for DNA-PK-Dependent and Independent DNA Double-Strand Break Repair Pathways in Mammalian Cells as a Function of the Cell Cycle  

Microsoft Academic Search

Mice homozygous for thescid(severe combined immune deficiency) mutation are defective in the repair of DNA double-strand breaks (DSBs) and are consequently very X-ray sensitive and defective in the lymphoid V(D)Jrecombinationprocess.Recently,astrongcandidateforthescidgenehasbeenidentifiedasthecatalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex. Here, we show that the activity of the DNA-PK complex is regulated in a cell cycle-dependent manner, with peaks of activity found

SANG EUN LEE; RACHEL A. MITCHELL; ANTHONY CHENG; ANDERIC A. HENDRICKSON

1997-01-01

312

Characteristics of photosynthesis and functions of the water-water cycle in rice (Oryza sativa) leaves in response to potassium deficiency.  

PubMed

The mechanisms of photoprotection of photosynthesis and dissipation of excitation energy in rice leaves in response to potassium (K) deficiency were investigated. Net photosynthetic rate and the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase decreased under K deficiency. Compared with the control, non-photochemical quenching of Chl fluorescence increased in K-deficient plant, whereas the efficiency of excitation transfer (F'(v)/F'(m)) and the photochemical quenching coefficient (q(P)) decreased. Thus, thermal dissipation of excitation energy increased as more excess electrons were accumulated in the photosynthetic chain. The electron transport rate through PSII (J(f)) was more sensitive to O2 concentration, and the fraction of electron transport rate required to sustain CO2 assimilation and photorespiration (J(g)/J(f)) was significantly decreased under K deficiency compared with the control. Furthermore, the alternative electron transport (J(a)/J(f)) was increased, indicating that a considerable amount of electrons had been transported to O2 during the water-water cycle in the K-deficient leaves. Although the fraction of electron transport to photorespiration (J(o)/J(f)) was also increased in the K-deficient leaves, it was less sensitive than that of the water-water cycle. With the generation of reactive oxygen species level, the activities of superoxide dismutase and ascorbate peroxidase, two of the key enzymes involved in scavenging of active oxygen species in the water-water cycle, also increased in K-deficient rice. Therefore, it is likely that a series of photoprotective mechanisms were initiated in rice plants in response to K deficiency and the water-water cycle might be critical for protecting photosynthetic apparatus under K deficiency in rice. PMID:18251852

Weng, Xiao-Yan; Zheng, Chen-Juan; Xu, Hong-Xia; Sun, Jian-Yi

2007-12-01

313

Influence of organic loading on an anaerobic sequencing biofilm batch reactor (ASBBR) as a function of cycle period and wastewater concentration.  

PubMed

The effect of organic loading on the performance of a mechanically stirred anaerobic sequencing biofilm batch reactor (ASBBR) has been investigated, by varying influent concentration and cycle period. For microbial immobilization 1-cm polyurethane foam cubes were used. An agitation rate of 500 rpm and temperature of 30+/-2 degrees C were employed. Organic loading rates (OLR) of 1.5-6.0gCODl(-1)d(-1) were applied to the 6.3-l reactor treating 2.0 l synthetic wastewater in 8 and 12-h batches and at concentrations of 500-2000mgCODl(-1), making it possible to analyze the effect of these two operation variables for the same organic loading range. Microbial immobilization on inert support maintained approximately 60 gTVS in the reactor. Filtered sample organic COD removal efficiencies ranged from 73 to 88% for organic loading up to 5.4gCODl(-1)d(-1). For higher organic loading (influent concentration of 2000mgCODl(-1) and 8-h cycle) the system presented total volatile acids accumulation, which reduced organics removal efficiency down to 55%. In this way, ASBBR with immobilized biomass was shown to be efficient for organic removal at organic loading rates of up to 5.4gCODl(-1)d(-1) and to be more stable to organic loading variations for 12-h cycles. This reactor might be an alternative to intermittent systems as it possesses greater operational flexibility. It might also be an alternative to batch systems suspended with microorganisms since it eliminates both the uncertainties regarding granulation and the time necessary for biomass sedimentation, hence reducing the total cycle period. PMID:15294356

Siman, Renato R; Borges, Alisson C; Ratusznei, Suzana M; Rodrigues, José A D; Zaiat, Marcelo; Foresti, Eugenio; Borzani, Walter

2004-09-01

314

X–ray structural analysis of the yeast cell cycle regulator Swi6 reveals variations of the ankyrin fold and has implications for Swi6 function  

Microsoft Academic Search

Swi6 is a 92,000 Mr protein common to two distinct transcriptional activation complexes (SBF and MBF) that coordinate gene expression at the G1–S boundary of the yeast cell cycle. The X–ray structure of a central 36,000 Mr fragment has been determined and refined at 2.1 Å resolution. The structure reveals a basic framework of five ankyrin repeat modules that is

Rachel Foord; Ian A. Taylor; Steven G. Sedgwick; Stephen J. Smerdon

1999-01-01

315

Interactive Effects of HDAC Inhibitors and TRAIL on Apoptosis Are Associated with Changes in Mitochondrial Functions and Expressions of Cell Cycle Regulatory Genes in Multiple Myeloma  

Microsoft Academic Search

In this study, we have evaluated the cytotoxic effect of combining two HDAC inhibitors, SAHA and TSA, with TRAIL in human multiple myeloma cell lines. Low doses of SAHA or TSA enhanced the cytotoxic and apoptotic effects of TRAIL and upregulated the surface expression of TRAIL death receptors (DR4 and\\/or DR5). SAHA and TSA induced G1 phase cell cycle growth

Tamer E. Fandy; Sharmila Shankar; Douglas D. Ross; Edward Sausville; Rakesh K. Srivastava

2005-01-01

316

Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle – structure\\/function study of Xenopus IRBP  

Microsoft Academic Search

BACKGROUND: Interphotoreceptor retinoid-binding protein's (IRBP) remarkable module structure may be critical to its role in mediating the transport of all-trans and 11-cis retinol, and 11-cis retinal between rods, cones, RPE and Müller cells during the visual cycle. We isolated cDNAs for Xenopus IRBP, and expressed and purified its individual modules, module combinations, and the full-length polypeptide. Binding of all-trans retinol,

Federico Gonzalez-Fernandez; Claxton A Baer; Debashis Ghosh

2007-01-01

317

Alcohol Consumption as a Function of Dietary Restraint and the Menstrual Cycle in Moderate/Heavy ("at-risk") Female Drinkers  

PubMed Central

Previous research suggests that women who report dietary restraint tend to consume alcohol in greater quantities, however most studies use retrospective data collection, which are often unreliable, and no studies have accounted for this relationship with respect to potential changes in alcohol consumption across the menstrual cycle. Therefore, the present study investigated the relationship between prospectively monitored drinking patterns and dietary restraint across the menstrual cycle among females from the general population whose drinking level (7 – 20 drinks/week) places them at-risk for developing alcohol use disorders. Restrained eaters (RES; N = 51) and unrestrained eaters (UN-RES; N = 55), per the cognitive restraint scale scores from the Three-Factor Eating Questionnaire, provided prospective ratings measuring mood, alcohol consumption, and consequences of alcohol use across one full menstrual cycle. Dysphoric mood increased during the late luteal and menstrual phases in both groups. Although overall the RES group did not drink more than the UN-RES group, the RES group drank less than the UN-RES group during the follicular phase, suggesting that among RES women alcohol consumption may be modulated by hormonal fluctuations across the menstrual cycle. The differences between the present findings and previous research may be due to the cohorts sampled; the majority of previous studies sampled college students, where binge drinking and dietary restraint are more common, whereas this study sampled the general population. Future research should replicate prior studies in a college-aged population using the current design of prospective data collection for greater accuracy of self-reported alcohol consumption.

DiMatteo, Julie; Reed, Stephanie Collins; Evans, Suzette M.

2012-01-01

318

Molecular Identification and Function of cis- and trans-Acting Determinants for petA Transcript Stability in Chlamydomonas reinhardtii Chloroplasts? †  

PubMed Central

In organelles, the posttranscriptional steps of gene expression are tightly controlled by nucleus-encoded factors, most often acting in a gene-specific manner. Despite the molecular identification of a growing number of factors, their mode of action remains largely unknown. In the green alga Chlamydomonas reinhardtii, expression of the chloroplast petA gene, which codes for cytochrome f, depends on two specific nucleus-encoded factors. MCA1 controls the accumulation of the transcript, while TCA1 is required for its translation. We report here the cloning of MCA1, the first pentatricopeptide repeat protein functionally identified in this organism. By chloroplast transformation with modified petA genes, we investigated the function of MCA1 in vivo. We demonstrate that MCA1 acts on the very first 21 nucleotides of the petA 5? untranslated region to protect the whole transcript from 5??3? degradation but does not process the 5? end of the petA mRNA. MCA1 and TCA1 recognize adjacent targets and probably interact together for efficient expression of petA mRNA. MCA1, although not strictly required for translation, shows features of a translational enhancer, presumably by assisting the binding of TCA1 to its own target. Conversely, TCA1 participates to the full stabilization of the transcript through its interaction with MCA1.

Loiselay, Christelle; Gumpel, Nicola J.; Girard-Bascou, Jacqueline; Watson, Adam T.; Purton, Saul; Wollman, Francis-Andre; Choquet, Yves

2008-01-01

319

Life cycle management of radioactive materials packaging  

Microsoft Academic Search

The objective of life cycle management of radioactive materials packaging is to ensure the safety functions (i.e. containment of radioactivity, protection against radiation, and criticality safety for fissile contents) during the entire life cycle of the packaging in storage, transportation and disposal. A framework has been developed for life cycle management regarding type B radioactive and fissile materials packaging, drawing

Y. Liu; S. Bellamy; J. Shuler

2007-01-01

320

Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity.  

PubMed

Cyclin D1 and its binding partners CDK4/6 are essential regulators of cell cycle progression and are implicated in cancer progression. Our aim was to investigate a potential regulatory role of these proteins in other essential tumor biological characteristics. Using a panel of breast cancer cell lines and primary human breast cancer samples, we have demonstrated the importance of these cell cycle regulators in both migration and stem-like cell activity. siRNA was used to target cyclin D1 and CDK4/6 expression, having opposing effects on both migration and stem-like cell activity dependent upon estrogen receptor (ER) expression. Inhibition of cyclin D1 or CDK4/6 increases or decreases migration and stem-like cell activity in ER-ve (ER-negative) and ER+ve (ER-positive) breast cancer, respectively. Furthermore, overexpressed cyclin D1 caused decreased migration and stem-like cell activity in ER-ve cells while increasing activity in ER+ve breast cancer cells. Treatment of breast cancer cells with inhibitors of cyclin D1 and CDK4/6 (Flavopiridol/PD0332991), currently in clinical trials, mimicked the effects observed with siRNA treatment. Re-expression of ER in two ER-ve cell lines was sufficient to overcome the effects of either siRNA or clinical inhibitors of cyclin D1 and CDK4/6.   In conclusion, cyclin D1 and CDK4/6 have alternate roles in regulation of migration and stem-like cell activity. Furthermore, these effects are highly dependent upon expression of ER. The significance of these results adds to our general understanding of cancer biology but, most importantly, could be used diagnostically to predict treatment response to cell cycle inhibition in breast cancer. PMID:23839043

Lamb, Rebecca; Lehn, Sophie; Rogerson, Lynsey; Clarke, Robert B; Landberg, Göran

2013-08-01

321

Tissue persistence and vaccine efficacy of tricarboxylic acid cycle and one-carbon metabolism mutant strains of Edwardsiella ictaluri.  

PubMed

Edwardsiella ictaluri causes enteric septicemia in fish. Recently, we reported construction of E. ictaluri mutants with single and double gene deletions in tricarboxylic acid cycle (TCA) and one-carbon (C-1) metabolism. Here, we report the tissue persistence, virulence, and vaccine efficacy of TCA cycle (Ei?sdhC, Ei?frdA, and Ei?mdh), C-1 metabolism (Ei?gcvP and Ei?glyA), and combination mutants (Ei?frdA?sdhC, Ei?gcvP?sdhC, Ei?mdh?sdhC, and Ei?gcvP?glyA) in channel catfish. The tissue persistence study showed that Ei?sdhC, Ei?frdA, Ei?frdA?sdhC, and Ei?gcvP?sdhC were able to invade catfish and persist until 11 days post-infection. Vaccination of catfish fingerlings with all nine mutants provided significant (P<0.05) protection against subsequent challenge with the virulent parental strain. Vaccinated catfish fingerlings had 100% survival when subsequently challenged by immersion with wild-type E. ictaluri except for Ei?gcvP?glyA and Ei?gcvP. Mutant Ei?gcvP?sdhC was found to be very good at protecting catfish fry, as evidenced by 10-fold higher survival compared to non-vaccinated fish. PMID:24837777

Dahal, Neeti; Abdelhamed, Hossam; Karsi, Attila; Lawrence, Mark L

2014-06-30

322

Functional Interactions between BM88/Cend1, Ran-Binding Protein M and Dyrk1B Kinase Affect Cyclin D1 Levels and Cell Cycle Progression/Exit in Mouse Neuroblastoma Cells  

PubMed Central

BM88/Cend1 is a neuronal-lineage specific modulator with a pivotal role in coordination of cell cycle exit and differentiation of neuronal precursors. In the current study we identified the signal transduction scaffolding protein Ran-binding protein M (RanBPM) as a BM88/Cend1 binding partner and showed that BM88/Cend1, RanBPM and the dual specificity tyrosine-phosphorylation regulated kinase 1B (Dyrk1B) are expressed in mouse brain as well as in cultured embryonic cortical neurons while RanBPM can form complexes with either of the two other proteins. To elucidate a potential mechanism involving BM88/Cend1, RanBPM and Dyrk1B in cell cycle progression/exit, we transiently co-expressed these proteins in mouse neuroblastoma Neuro 2a cells. We found that the BM88/Cend1-dependent or Dyrk1B-dependent down-regulation of cyclin D1 is reversed following their functional interaction with RanBPM. More specifically, functional interaction of RanBPM with either BM88/Cend1 or Dyrk1B stabilizes cyclin D1 in the nucleus and promotes 5-bromo-2'-deoxyuridine (BrdU) incorporation as a measure of enhanced cell proliferation. However, the RanBPM-dependent Dyrk1B cytosolic retention and degradation is reverted in the presence of Cend1 resulting in cyclin D1 destabilization. Co-expression of RanBPM with either BM88/Cend1 or Dyrk1B also had a negative effect on Neuro 2a cell differentiation. Our results suggest that functional interactions between BM88/Cend1, RanBPM and Dyrk1B affect the balance between cellular proliferation and differentiation in Neuro 2a cells and indicate that a potentially similar mechanism may influence cell cycle progression/exit and differentiation of neuronal precursors.

Tsioras, Konstantinos; Papastefanaki, Florentia; Politis, Panagiotis K.; Matsas, Rebecca; Gaitanou, Maria

2013-01-01

323

Advanced regenerative absorption refrigeration cycles  

DOEpatents

Multi-effect regenerative absorption cycles which provide a high coefficient of performance (COP) at relatively high input temperatures. An absorber-coupled double-effect regenerative cycle (ADR cycle) (10) is provided having a single-effect absorption cycle (SEA cycle) (11) as a topping subcycle and a single-effect regenerative absorption cycle (1R cycle) (12) as a bottoming subcycle. The SEA cycle (11) includes a boiler (13), a condenser (21), an expansion device (28), an evaporator (31), and an absorber (40), all operatively connected together. The 1R cycle (12) includes a multistage boiler (48), a multi-stage resorber (51), a multisection regenerator (49) and also uses the condenser (21), expansion device (28) and evaporator (31) of the SEA topping subcycle (11), all operatively connected together. External heat is applied to the SEA boiler (13) for operation up to about 500 degrees F., with most of the high pressure vapor going to the condenser (21) and evaporator (31) being generated by the regenerator (49). The substantially adiabatic and isothermal functioning of the SER subcycle (12) provides a high COP. For higher input temperatures of up to 700 degrees F., another SEA cycle (111) is used as a topping subcycle, with the absorber (140) of the topping subcycle being heat coupled to the boiler (13) of an ADR cycle (10). The 1R cycle (12) itself is an improvement in that all resorber stages (50b-f) have a portion of their output pumped to boiling conduits (71a-f) through the regenerator (49), which conduits are connected to and at the same pressure as the highest pressure stage (48a) of the 1R multistage boiler (48).

Dao, Kim (14 Nace Ave., Piedmont, CA 94611) [14 Nace Ave., Piedmont, CA 94611

1990-01-01

324

Functional HSF1 Requires Aromatic-Participant Interactions in Protecting Mouse Embryonic Fibroblasts against Apoptosis Via G2 Cell Cycle Arrest  

PubMed Central

The present study highlighted the aromatic-participant interactions in in vivo trimerization of HSF1 and got an insight into the process of HSF1 protecting against apoptosis. In mouse embryonic fibroblasts (MEFs), mutations of mouse HSF1 (W37A, Y60A and F104A) resulted in a loss of trimerization activity, impaired binding of the heat shock element (HSE) and lack of heat shock protein 70 (HSP70) expression after a heat shock. Under UV irradiation, wild-type mouse HSF1 protected the MEFs from UV-induced apoptosis, but none of the mutants offered protection. We found that normal expression of HSF1 was essential to the cell arrest in G2 phase, assisting with the cell cycle checkpoint. The cells that lack normal HSF1 failed to arrest in the G2 phase, resulting in the process of cell apoptosis. We conclude that the treatment with UV or heat shock stresses appears to induce the approach of HSF1 monomers directly via aromatic-participant interactions, followed by the formation of a HSF1 trimer. HSF1 protects the MEFs from the stresses through the expression of HSPs and a G2 cell cycle arrest.

Chang, Ziwei; Lu, Ming; Park, Sung-Min; Park, Hyun-Kyung; Kang, Ho Sung; Pak, Youngshang; Park, Jang-Su

2012-01-01

325

The photochemical cycle of bacteriorhodopsin  

NASA Technical Reports Server (NTRS)

The reaction cycle of bacteriorhodopsin in the purple membrane isolated from Halobacterium halobium has been studied by optical absorption spectroscopy using low-temperature and flash kinetic techniques. After absorption of light, bacteriorhodopsin passes through at least five distinct intermediates. The temperature and pH dependence of the absorbance changes suggests that branch points and/or reversible steps exist in this cycle. Flash spectroscopy in the presence of a pH-indicating dye shows that the transient release of a proton accompanies the photoreaction cycle. The proton release occurs from the exterior and the uptake is on the cytoplasmic side of the membrane, as required by the function of bacteriorhodopsin as a light-driven proton pump. Proton translocating steps connecting release and uptake are indicated by deuterium isotope effects on the kinetics of the cycle. The rapid decay of a light-induced linear dichroism shows that a chromophore orientation change occurs during the reaction cycle.

Lozier, R. H.; Niederberger, W.

1977-01-01

326

Large-scale brain functional modularity is reflected in slow electroencephalographic rhythms across the human non-rapid eye movement sleep cycle.  

PubMed

Large-scale brain functional networks (measured with functional magnetic resonance imaging, fMRI) are organized into separated but interacting modules, an architecture supporting the integration of distinct dynamical processes. In this work we study how the aforementioned modular architecture changes with the progressive loss of vigilance occurring in the descent to deep sleep and we examine the relationship between the ensuing slow electroencephalographic rhythms and large-scale network modularity as measured with fMRI. Graph theoretical methods are used to analyze functional connectivity graphs obtained from fifty-five participants at wakefulness, light and deep sleep. Network modularity (a measure of functional segregation) was found to increase during deeper sleep stages but not in light sleep. By endowing functional networks with dynamical properties, we found a direct link between increased electroencephalographic (EEG) delta power (1-4 Hz) and a breakdown of inter-modular connectivity. Both EEG slowing and increased network modularity were found to quickly decrease during awakenings from deep sleep to wakefulness, in a highly coordinated fashion. Studying the modular structure itself by means of a permutation test, we revealed different module memberships when deep sleep was compared to wakefulness. Analysis of node roles in the modular structure revealed an increase in the number of locally well-connected nodes and a decrease in the number of globally well-connected hubs, which hinders interactions between separated functional modules. Our results reveal a well-defined sequence of changes in brain modular organization occurring during the descent to sleep and establish a close parallel between modularity alterations in large-scale functional networks (accessible through whole brain fMRI recordings) and the slowing of scalp oscillations (visible on EEG). The observed re-arrangement of connectivity might play an important role in the processes underlying loss of vigilance and sensory awareness during deep sleep. PMID:23313420

Tagliazucchi, Enzo; von Wegner, Frederic; Morzelewski, Astrid; Brodbeck, Verena; Borisov, Sergey; Jahnke, Kolja; Laufs, Helmut

2013-04-15

327

Bioremediation of chlorimuron-ethyl-contaminated soil by Hansschlegelia sp. strain CHL1 and the changes of indigenous microbial population and N-cycling function genes during the bioremediation process.  

PubMed

Long-term and excessive application of the herbicide chlorimuron-ethyl has led to soil degradation and crop rotation barriers. In the current study, we isolated bacterial strain Hansschlegelia sp. CHL1, which can utilize chlorimuron-ethyl as its sole carbon and energy source, and investigated its application in soil bioremediation. Indigenous microbial populations and N-cycling function in the soil were also investigated during the bioremediation process by monitoring the copy numbers of bacterial and fungal marker genes, as well as N-cycling functional genes (nifH, amoA, nirS, and nirK). Results showed that >95% of chlorimuron-ethyl could be degraded within 45 days in soils inoculated with CHL1. Inoculation at two time points resulted in a higher remediation efficiency and longer survival time than a single inoculation. At the end of the 60-day incubation, the copy numbers of most indicator genes were recovered to the level of the control, even in the single-inoculation soils. A double inoculation was necessary for recovery of nifH. However, the abundance of nirK and ammonia-oxidizing bacterial genes were significantly inhibited regardless of inoculum. The results suggested that CHL1 is effective for the remediation of chlorimuron-ethyl-contaminated soil, and could partially reduce the toxic effects of chlorimuron-ethyl on soil microorganisms. PMID:24794985

Yang, Liqiang; Li, Xinyu; Li, Xu; Su, Zhencheng; Zhang, Chenggang; Zhang, Huiwen

2014-06-15

328

Reformulation, as a Function of Only Working Temperatures, of Performance Parameters of a Solar Driven Ejector-Absorption Cycle Using Artificial Neural Networks  

Microsoft Academic Search

Theoretical thermodynamic analysis of the absorption thermal systems is too complex because of analytic functions calculating the thermodynamic properties of fluid couples involving the solution of complex differential equations and simulations programs. This article proposes a new approach to performance analysis of solar driven ejector-absorption refrigeration system (EARS) operated aqua\\/ammonia. Use of artificial neural networks (ANNs) has been proposed to

Adnan Sözen; M. Ali Akçayol

2005-01-01

329

Sensitivity of C3H 10T1/2 cells to radiation-induced killing and neoplastic transformation as a function of cell cycle.  

PubMed

Cell-age sensitivity to both cell killing and neoplastic transformation induced by radiation was investigated using synchronized populations of C3H10T1/2 cells. Mitotic-cell suspensions, collected using a mitotic shake-off procedure, were irradiated with 4Gy 250 kVp X-rays or 0.5 Gy fission neutrons from the RSV-TAPIRO reactor at CR-Casaccia. For study of cell killing the mitotic-cell suspensions were either irradiated immediately after collection, or plated for subsequent irradiation, which was performed every hour, covering an interval of 17 h. The response pattern observed was similar after X-rays and neutron irradiation, but the magnitude of the variation through the cell cycle was smaller in the case of neutrons (1.3- compared with 5-fold). For study of neoplastic transformation induction the irradiation was performed immediately after collection, i.e. in M phase, or at later times corresponding to mid-G1, G1/S and G2 phases. The sensitivity of the G2/M phase was examined by irradiating the cells with 4Gy X-rays while still attached to the flask bottom, and dislodging them after 25 min. SimilarLy to cell survival, the transformation frequency showed a small variation after neutron irradiation (1.4- compared with 3.1-fold) for the phases examined. PMID:8601756

Pazzaglia, S; Saran, A; Pariset, L; Rebessi, S; Di Majo, V; Coppola, M; Covelli, V

1996-01-01

330

Evidence for DNA-PK-dependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle.  

PubMed Central

Mice homozygous for the scid (severe combined immune deficiency) mutation are defective in the repair of DNA double-strand breaks (DSBs) and are consequently very X-ray sensitive and defective in the lymphoid V(D)J recombination process. Recently, a strong candidate for the scid gene has been identified as the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex. Here, we show that the activity of the DNA-PK complex is regulated in a cell cycle-dependent manner, with peaks of activity found at the G1/early S phase and again at the G2 phase in wild-type cells. Interestingly, only the deficit of the G1/early S phase DNA-PK activity correlated with an increased hypersensitivity to X-irradiation and a DNA DSB repair deficit in synchronized scid pre-B cells. Finally, we demonstrate that the DNA-PK activity found at the G2 phase may be required for exit from a DNA damage-induced G2 checkpoint arrest. These observations suggest the presence of two pathways (DNA-PK-dependent and -independent) of illegitimate mammalian DNA DSB repair and two distinct roles (DNA DSB repair and G2 checkpoint traversal) for DNA-PK in the cellular response to ionizing radiation.

Lee, S E; Mitchell, R A; Cheng, A; Hendrickson, E A

1997-01-01

331

Photoperiodic induction in quail as a function of the period of the light-dark cycle: implications for models of time measurement.  

PubMed

The earliest detectable event in the photoperiodic response of quail is a rise in luteinizing hormone (LH) secretion beginning at about hour 20 on the first long day. The timing of this rise was measured in castrated quail after entrainment to short daylengths which cause significant phase angle differences in the circadian system: (1) LD 2:22 and LD 10:14, and (2) LD 3:21 (T = 24 hr) and LD 3:24 (T = 27 hr). The quail were then exposed to 24 hr of light (by delaying lights-off), and the time of the first LH rise was measured; it was similar in all schedules. Quail were also entrained to LD 3:21 or LD 3:24 and then given a single 6-hr nightbreak 6-12, 7-13, or 13-19 hr after dawn. The earlier pulse was marginally more inductive in the 27-hr cycle. Thus the entrainment characteristics of the photoinducible rhythm (phi i) in quail appear very different from those of the locomotor circadian rhythm, and raise doubts as to whether phi i is a primary circadian oscillator. PMID:1773099

Follett, B K; Pearce-Kelly, A S

1991-01-01

332

Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo 31P nuclear magnetic resonance and electron paramagnetic resonance spectroscopy.  

PubMed

Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance ((31)P NMR) spectroscopy to noninvasively measure high-energy phosphate levels; mitochondrial aconitase activity measurements that directly correlate with TCA cycle flux, as measured by gas chromatography mass spectrometry (GC-MS); and electron paramagnetic resonance (EPR) to assess oxidative stress. At 6 h postburn, the oxidative ATP synthesis rate was increased 5-fold in burned mice given a single dose of SS-31 relative to untreated burned mice (P=0.002). Furthermore, SS-31 administration in burned animals decreased mitochondrial aconitase activity back to control levels. EPR revealed a recovery in redox status of the SS-31-treated burn group compared to the untreated burn group (P<0.05). Our multidisciplinary convergent results suggest that SS-31 promotes recovery of mitochondrial function after burn injury by increasing ATP synthesis rate, improving mitochondrial redox status, and restoring mitochondrial coupling. These findings suggest use of noninvasive in vivo NMR and complementary EPR offers an approach to monitor the effectiveness of mitochondrial protective agents in alleviating burn injury symptoms. PMID:23482635

Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Khan, Nadeem; Mupparaju, S P; Rahme, Laurence G; Swartz, Harold M; Szeto, Hazel H; Tompkins, Ronald G; Tzika, A Aria

2013-06-01

333

A Synthesis of Solar Cycle Prediction Techniques  

NASA Technical Reports Server (NTRS)

A number of techniques currently in use for predicting solar activity on a solar cycle timescale are tested with historical data. Some techniques, e.g., regression and curve fitting, work well as solar activity approaches maximum and provide a month-by-month description of future activity, while others, e.g., geomagnetic precursors, work well near solar minimum but only provide an estimate of the amplitude of the cycle. A synthesis of different techniques is shown to provide a more accurate and useful forecast of solar cycle activity levels. A combination of two uncorrelated geomagnetic precursor techniques provides a more accurate prediction for the amplitude of a solar activity cycle at a time well before activity minimum. This combined precursor method gives a smoothed sunspot number maximum of 154 plus or minus 21 at the 95% level of confidence for the next cycle maximum. A mathematical function dependent on the time of cycle initiation and the cycle amplitude is used to describe the level of solar activity month by month for the next cycle. As the time of cycle maximum approaches a better estimate of the cycle activity is obtained by including the fit between previous activity levels and this function. This Combined Solar Cycle Activity Forecast gives, as of January 1999, a smoothed sunspot maximum of 146 plus or minus 20 at the 95% level of confidence for the next cycle maximum.

Hathaway, David H.; Wilson, Robert M.; Reichmann, Edwin J.

1999-01-01

334

Algae displaying the diadinoxanthin cycle also possess the violaxanthin cycle  

PubMed Central

According to general agreement, all photosynthetic organisms using xanthophyll cycling for photoprotection contain either the violaxanthin (Vx) cycle or the diadinoxanthin (Ddx) cycle instead. Here, we report the temporal accumulation of substantial amounts of pigments of the Vx cycle under prolonged high-light stress in several microalgae thought to possess only the Ddx cycle. In the diatom Phaeodactylum tricornutum, used as a model organism, these pigments also participate in xanthophyll cycling, and their accumulation depends on de novo synthesis of carotenoids and on deepoxidase activity. Furthermore, our data strongly suggest a biosynthetic sequence from Vx via Ddx to fucoxanthin in P. tricornutum. This gives experimental support to the long-stated hypothesis that Vx is a common precursor of all carotenoids with an allenic or acetylenic group, including the main light-harvesting carotenoids in most chlorophyll a/c-containing algae. Thus, another important function for xanthophyll cycling may be to optimize the biosynthesis of light-harvesting xanthophylls under fluctuating light conditions.

Lohr, Martin; Wilhelm, Christian

1999-01-01

335

Classification of a frameshift/extended and a stop mutation in WT1 as gain-of-function mutations that activate cell cycle genes and promote Wilms tumour cell proliferation.  

PubMed

The WT1 gene encodes a zinc finger transcription factor important for normal kidney development. WT1 is a suppressor for Wilms tumour development and an oncogene for diverse malignant tumours. We recently established cell lines from primary Wilms tumours with different WT1 mutations. To investigate the function of mutant WT1 proteins, we performed WT1 knockdown experiments in cell lines with a frameshift/extension (p.V432fsX87 = Wilms3) and a stop mutation (p.P362X = Wilms2) of WT1, followed by genome-wide gene expression analysis. We also expressed wild-type and mutant WT1 proteins in human mesenchymal stem cells and established gene expression profiles. A detailed analysis of gene expression data enabled us to classify the WT1 mutations as gain-of-function mutations. The mutant WT1(Wilms2) and WT1(Wilms3) proteins acquired an ability to modulate the expression of a highly significant number of genes from the G2/M phase of the cell cycle, and WT1 knockdown experiments showed that they are required for Wilms tumour cell proliferation. p53 negatively regulates the activity of a large number of these genes that are also part of a core proliferation cluster in diverse human cancers. Our data strongly suggest that mutant WT1 proteins facilitate expression of these cell cycle genes by antagonizing transcriptional repression mediated by p53. We show that mutant WT1 can physically interact with p53. Together the findings show for the first time that mutant WT1 proteins have a gain-of-function and act as oncogenes for Wilms tumour development by regulating Wilms tumour cell proliferation. PMID:24619359

Busch, Maike; Schwindt, Heinrich; Brandt, Artur; Beier, Manfred; Görldt, Nicole; Romaniuk, Paul; Toska, Eneda; Roberts, Stefan; Royer, Hans-Dieter; Royer-Pokora, Brigitte

2014-08-01

336

Classification of a frameshift/extended and a stop mutation in WT1 as gain-of-function mutations that activate cell cycle genes and promote Wilms tumour cell proliferation  

PubMed Central

The WT1 gene encodes a zinc finger transcription factor important for normal kidney development. WT1 is a suppressor for Wilms tumour development and an oncogene for diverse malignant tumours. We recently established cell lines from primary Wilms tumours with different WT1 mutations. To investigate the function of mutant WT1 proteins, we performed WT1 knockdown experiments in cell lines with a frameshift/extension (p.V432fsX87 = Wilms3) and a stop mutation (p.P362X = Wilms2) of WT1, followed by genome-wide gene expression analysis. We also expressed wild-type and mutant WT1 proteins in human mesenchymal stem cells and established gene expression profiles. A detailed analysis of gene expression data enabled us to classify the WT1 mutations as gain-of-function mutations. The mutant WT1Wilms2 and WT1Wilms3 proteins acquired an ability to modulate the expression of a highly significant number of genes from the G2/M phase of the cell cycle, and WT1 knockdown experiments showed that they are required for Wilms tumour cell proliferation. p53 negatively regulates the activity of a large number of these genes that are also part of a core proliferation cluster in diverse human cancers. Our data strongly suggest that mutant WT1 proteins facilitate expression of these cell cycle genes by antagonizing transcriptional repression mediated by p53. We show that mutant WT1 can physically interact with p53. Together the findings show for the first time that mutant WT1 proteins have a gain-of-function and act as oncogenes for Wilms tumour development by regulating Wilms tumour cell proliferation.

Busch, Maike; Schwindt, Heinrich; Brandt, Artur; Beier, Manfred; Gorldt, Nicole; Romaniuk, Paul; Toska, Eneda; Roberts, Stefan; Royer, Hans-Dieter; Royer-Pokora, Brigitte

2014-01-01

337

Functional expression of a biologically active fragment of soluble gp130 as an ELP-fusion protein in transgenic plants: purification via inverse transition cycling  

PubMed Central

In murine models of Crohn's disease, rheumatoid arthritis and colon cancer, IL-6 (interleukin-6) signalling via the sIL-6R (soluble IL-6 receptor; termed IL-6 trans-signalling) has been shown to promote the pathology associated with these conditions. These detrimental activities can, however, be selectively blocked by soluble forms of the gp130 (glycoprotein 130) receptor. Although sgp130 (soluble gp130) therefore represents a viable therapeutic modality for the treatment of these conditions, the mass manufacture of such biologics is often expensive. The advent of molecular farming has, however, provided an extremely cost-effective strategy for the engineering of recombinant proteins. Here, we describe the expression and production of a biologically active sgp130 variant that is expressed in transgenic tobacco plants as an ELP (elastin-like peptide)-fusion protein (mini-gp130–ELP). Mini-gp130–ELP consists of the first three domains of gp130 (Ig-like domain and cytokine binding module) fused to 100 repeats of ELP. Expression of mini-gp130–ELP did not affect the growth rate or morphology of the transgenic plants, and purification was achieved using inverse transition cycling. This approach led to an overall yield of 141 ?g of purified protein per g of fresh leaf weight. The purified mini-gp130–ELP specifically inhibited sIL-6R-mediated trans-signalling as measured by binding to the IL-6–sIL-6R complex and through its ability to block sIL-6R-mediated activation of STAT3 (signal transducer and activator of transcription 3) phosphorylation and proliferation in human hepatoma cells and murine pre-B-cells. Consequently, the present study validates the potential application of molecular farming in transgenic tobacco plants as a strategy for the expression and purification of therapeutically advantageous biologics such as sgp130.

Lin, Meng; Rose-John, Stefan; Grotzinger, Joachim; Conrad, Udo; Scheller, Jurgen

2006-01-01

338

Hypothalamic-pituitary-adrenal (HPA) axis function in the California mouse (Peromyscus californicus): Changes in baseline activity, reactivity, and fecal excretion of glucocorticoids across the diurnal cycle  

PubMed Central

The California mouse, Peromyscus californicus, is an increasingly popular animal model in behavioral, neural, and endocrine studies, but little is known about its baseline hypothalamicpituitary-adrenal (HPA) axis activity or HPA responses to stressors. We characterized plasma corticosterone (CORT) concentrations in P. californicus under baseline conditions across the diurnal cycle, in response to pharmacological manipulation of the HPA axis, and in response to a variety of stressors at different times of day. In addition, we explored the use of fecal samples to monitor adrenocortical activity non-invasively. California mice have very high baseline levels of circulating CORT that change markedly over 24 hours, but that do not differ between the sexes. This species may be somewhat glucocorticoid-resistant in comparison to other rodents as a relatively high dose of dexamethasone (5 mg/kg, s.c.) was required to suppress plasma CORT for 8 h post-injection. CORT responses to stressors and ACTH injection differed with time of day, as CORT concentrations were elevated more readily during the morning (inactive period) than in the evening (active period) when compared to time-matched control. Data from 3H-CORT injection studies show that the time course for excretion of fecal CORT, or glucocorticoid metabolites, differs with time of injection. Mice injected in the evening excreted the majority of fecal radioactivity 2–4 h post-injection whereas mice injected during the morning did so at 14–16 h post-injection. Unfortunately, the antibody we used does not adequately bind the most prevalent fecal glucocorticoid metabolites and therefore we could not validate its use for fecal assays.

Harris, Breanna N.; Saltzman, Wendy; de Jong, Trynke R.; Milnes, Matthew R.

2012-01-01

339

In vivo effects of the soluble fraction of light cycle oil on immune functions in the European sea bass, Dicentrarchus labrax (Linné).  

PubMed

Hydrocarbons are major contaminants that may affect biota at various trophic levels in estuaries and coastal ecosystems. The effects of accidental pollution by light cycle oil (LCO), a refined product of heavy fuel oil, on bioaccumulation, depuration processes and immune-related parameters in the European sea bass, Dicentrarchus labrax, were investigated in the laboratory after 7 days of exposure and a 2-week recovery period. Exposure of fish to the soluble fraction of LCO (1600ngL(-1)) for 7 days led to the bioaccumulation of some polycyclic aromatic hydrocarbons (PAHs) in muscles: naphthalene, acenaphthene, fluorene, phenanthrene and anthracene. After 7 days of recovery period, half-elimination of naphthalene was reported in fish muscles due to facilitated diffusive loss by the epithelium and a faster elimination rate proven by the presence of a high level of naphthalene biliary metabolites. The other bioaccumulated molecules displayed a slower depuration rate due to their elimination by the formation of hydrophobic metabolites excreted through bile or urine. Three days after the beginning of the recovery period, each contaminated fish showed severe external lesions (tissue necrosis, suppurative exudates, haemorrhagic area). The hypothesis of a possible link with inflammatory phenomenon was supported by (i) an inversion of the leucocyte sub-population percentage, (ii) a significant up-expression in the spleen of the tumour necrosis factor alpha gene, (iii) a significant increase in ACH(50). Moreover, the lack of C3 gene regulation in the spleen suggested a non-renewal of this component. The reduction of phagocytic activity and lysozyme concentration reflected immune suppression. Finally, LCO toxicity in this fish was clearly demonstrated to be related to inflammatory reaction and immune depletion. PMID:21764455

Bado-Nilles, Anne; Quentel, Claire; Mazurais, David; Zambonino-Infante, José Luis; Auffret, Michel; Thomas-Guyon, Hélène; Le Floch, Stéphane

2011-10-01

340

Research on the effect of life cycle gaps on life cycle cost of urban infrastructure engineering  

Microsoft Academic Search

Life Cycle Cost optimization has become a new focus of urban infrastructure engineering economic study. This paper shows the replacement reasons and preferences related to the different type of life cycle by studying literatures. It is clear by analyzing a basic LCC model that sensitivity of the LCC functions on life cycle gaps is less than the discount rate when

Weiyi He; Yilin Yin

2009-01-01

341

Genetic Evidence for Bacterial Chemolithoautotrophy Based on the Reductive Tricarboxylic Acid Cycle in Groundwater Systems  

PubMed Central

Geologically and chemically distinct aquifers were screened for the presence of two genes coding for key enzymes of the reverse tricarboxylic acid (rTCA) cycle in autotrophic bacteria, 2-oxoglutarate : ferredoxin oxidoreductase (oorA) and the beta subunit of ATP citrate lyase enzymes (aclB). From 42 samples investigated, aclB genes were detected in two and oorA genes in six samples retrieved from polluted and sulfidic aquifers. aclB genes were represented by a single phylotype of almost identical sequences closely affiliated with chemolithoautotrophic Sulfurimonas species. In contrast, sequences analysis of oorA genes revealed diverse phylotypes mainly related to sequences from cultivation-independent studies.

Alfreider, Albin; Vogt, Carsten

2012-01-01

342

Carbon cycling and carbon metabolism by soil fungi in a boreal forest: impacts of wildfire and permafrost on functional genes, isotope signatures, and ectomycorrhizae  

NASA Astrophysics Data System (ADS)

Understanding the mechanisms that control the stabilization and destabilization of soil carbon within boreal forest ecosystems is of great importance to the global carbon budget. Much is currently known about boreal soil carbon dynamics in relation to biophysical and landscape variables such as temperature, moisture, wildfire intensity, and stand age. We have less information regarding the controls on decomposition at the molecular scale, where interactions between microbial communities, their genetic `potential' for decomposition, functional genes, enzyme synthesis, and organic matter transformations occur. We have entered an age in which these connections can be made at the molecular scale, but what form do they take, and can they scale up to affect carbon dynamics at the level of the ecosystem? We examined these molecular scale processes in mature boreal forest soils and soils that had been impacted by wildfire near Delta Junction, Alaska. We also examined the interactive effect of permafrost presence, which reduces soil drainage, with wildfire. We focused on three themes: linking microbial communities and laccase functional genes to soil laccase enzyme activity and lignin decomposition, assessing substrate availability using the natural abundance ?13C isotope ratios of microbial biomass, and the influence of ectomycorrhizal mats on decomposition. Wildfire reduced fungal biomass, laccase functional gene abundance, laccase activity, and ?13C-lignin decomposition. Relationships between gene abundance and microbial activity were significant and logarithmic in form. Soil drainage, which is mediated by the presence of permafrost, had little effect on the abundance of fungi, functional genes, or potential process rates. Microbial biomass ?13C was always enriched relative to soil organic matter, and this difference was greater in control soils compared to wildfire-affected soils, indicating that Ä??13C MB-SOIL may indicate the level of bioavailability of soil carbon for microbial metabolism. Ectomycorrhizal mats occurred only in control soils and increased fungal biomass, functional gene abundance, enzyme activities and process rates compared to non-mat soils. Taken together these results indicate that linkages can be made between the distribution of soil microbial communities, molecular scale information, and soil carbon dynamics.

Waldrop, M. P.; Harden, J. W.

2006-12-01

343

Prebiotic metabolism: production by mineral photoelectrochemistry of alpha-ketocarboxylic acids in the reductive tricarboxylic acid cycle.  

PubMed

A reductive tricarboxylic acid (rTCA) cycle could have fixed carbon dioxide as biochemically useful energy-storage molecules on early Earth. Nonenzymatic chemical pathways for some steps of the rTCA cycle, however, such as the production of the alpha-ketocarboxylic acids pyruvate and alpha-ketoglutarate, remain a challenging problem for the viability of the proposed prebiotic cycle. As a class of compounds, alpha-ketocarboxylic acids have high free energies of formation that disfavor their production. We report herein the production of pyruvate from lactate and of alpha-ketoglutarate from pyruvate in the millimolar concentration range as promoted by ZnS mineral photoelectrochemistry. Pyruvate is produced from the photooxidation of lactate with 70% yield and a quantum efficiency of 0.009 at 15 degrees C across the wavelength range of 200-400 nm. The produced pyruvate undergoes photoreductive back reaction to lactate at a 30% yield and with a quantum efficiency of 0.0024. Pyruvate alternatively continues in photooxidative forward reaction to alpha-ketoglutarate with a 50% yield and a quantum efficiency of 0.0036. The remaining 20% of the carbon follows side reactions that produce isocitrate, glutarate, and succinate. Small amounts of acetate are also produced. The results of this study suggest that alpha-ketocarboxylic acids produced by mineral photoelectrochemistry could have participated in a viable enzyme-free cycle for carbon fixation in an environment where light, sulfide minerals, carbon dioxide, and other organic compounds interacted on prebiotic Earth. PMID:19968461

Guzman, Marcelo I; Martin, Scot T

2009-11-01

344

The Q-cycle reviewed: how well does a monomeric mechanism of the bc1 complex account for the function of a dimeric complex?  

PubMed Central

Recent progress in understanding the Q-cycle mechanism of the bc1 complex is reviewed. The data strongly support a mechanism in which the Qo-site operates through a reaction in which the first electron transfer from ubiquinol to the oxidized iron-sulfur protein is the rate determining step for the overall process. The reaction involves a proton-coupled electron transfer down a hydrogen bond between the ubiquinol and a histidine ligand of the [2Fe-2S] cluster, in which the unfavorable protonic configuration contributes a substantial part of the activation barrier. The reaction is endergonic, and the products are an unstable ubisemiquinone at the Qo-site, and the reduced iron-sulfur protein, the extrinsic mobile domain of which is now free to dissociate and move away from the site to deliver an electron to cyt c1 and liberate the H+. When oxidation of the semiquinone is prevented, it participates in bypass reactions, including superoxide generation if O2 is available. When the b-heme chain is available as acceptor, the semiquinone is oxidized in a process in which the proton is passed to the glutamate of the conserved –PEWY- sequence, and the semiquinone anion passes its electron to heme bL to form the product ubiquinone. The rate is rapid compared to the limiting reaction, and would require movement of the semiquinone closer to heme bL to enhance the rate constant. The acceptor reactions at the Qi-site are still controversial, but likely involve a “two-electron gate” in which a stable semiquinone stores an electron. Possible mechanisms to explain the cytb150 phenomenon are discussed, and the information from pulsed EPR studies about the structure of the intermediate state is reviewed. The mechanism discussed is applicable to a monomeric bc1 complex. We discuss evidence in the literature that has been interpreted as shown that the dimeric structure participates in a more complicated mechanism involving electron transfer across the dimer interface. We show from myxothiazol titrations and mutational analysis of Tyr-199, which is at the interface between monomers, that no such inter-monomer electron transfer is detected at the level of the bL hemes. We show from analysis of strains with mutations at Asn-221 that there are coulombic interactions between the b-hemes in a monomer. The data can also be interpreted as showing similar coulombic interaction across the dimer interface, and we discuss mechanistic implications.

Crofts, Antony R.; Holland, J. Todd; Victoria, Doreen; Kolling, Derrick R.J.; Dikanov, Sergei A.; Gilbreth, Ryan; Lhee, Sangmoon; Kuras, Richard; Kuras, Mariana Guergova

2008-01-01

345

A Functional Calvin Cycle Is Not Indispensable for the Light Activation of C4 Phosphoenolpyruvate Carboxylase Kinase and Its Target Enzyme in the Maize Mutant bundle sheath defective2-mutable11  

PubMed Central

We used a pale-green maize (Zea mays L.) mutant that fails to accumulate ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to test the working hypothesis that the regulatory phosphorylation of C4 phosphoenolpyruvate carboxylase (PEPC) by its Ca2+-insensitive protein-serine/threonine kinase (PEPC kinase) in the C4 mesophyll cytosol depends on cross-talk with a functional Calvin cycle in the bundle sheath. Wild-type (W22) and bundle sheath defective2-mutable1 (bsd2-m1) seeds were grown in a controlled environment chamber at 100 to 130 ?mol m?2 s?1 photosynthetic photon flux density, and leaf tissue was harvested 11 d after sowing, following exposure to various light intensities. Immunoblot analysis showed no major difference in the amount of polypeptide present for several mesophyll- and bundle-sheath-specific photosynthetic enzymes apart from Rubisco, which was either completely absent or very much reduced in the mutant. Similarly, leaf net CO2-exchange analysis and in vitro radiometric Rubisco assays showed that no appreciable carbon fixation was occurring in the mutant. In contrast, the sensitivity of PEPC to malate inhibition in bsd2-m1 leaves decreased significantly with an increase in light intensity, and there was a concomitant increase in PEPC kinase activity, similar to that seen in wild-type leaf tissue. Thus, although bsd2-m1 mutant plants lack an operative Calvin cycle, light activation of PEPC kinase and its target enzyme are not grossly perturbed.

Smith, Lucy H.; Langdale, Jane A.; Chollet, Raymond

1998-01-01

346

Anti cancer effects of curcumin: cycle of life and death  

Microsoft Academic Search

Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter cell cycle regulatory molecules, in cancer therapy. Most human malignancies are driven by chromosomal translocations or other genetic alterations that directly affect the function of critical cell cycle proteins such as

Gaurisankar Sa; Tanya Das

2008-01-01

347

Thirstin's Water Cycle  

NSDL National Science Digital Library

The representation is an animation of the water cycle. The user can select individual parts, such as: rain, water vapor, water storage and clouds. The user can observe water as it cycles through the various parts of the water cycle.

348

Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection.  

PubMed Central

Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele of the chemokine coreceptor CCR-5 as efficiently as it infects macaque cells expressing human CD4, suggesting that SIV can function with either a simian or a human coreceptor in conjunction with human CD4. In the same macaque cells expressing human CD4, the replication of human immunodeficiency virus type 1 (HIV-1) is blocked at several stages of infection; some isolates are restricted prior to reverse transcription, while others, including some macrophage-tropic and primary isolates, are restricted at a step after reverse transcription but prior to migration of the preintegration complex to the nucleus. Both blocks in HIV-1 replication can be relieved by either expression of the appropriate human coreceptor (CCR-5 or CXCR-4) or expression of SIV gene products in cis with the HIV-1 envelope as a chimera between SIV and HIV-1 (SHIV). Thus, a virus with a SIV core and HIV-1 envelope can efficiently infect macaque cells expressing human CD4, presumably by interacting with the simian coreceptor, whereas a virus with an HIV-1 core and an HIV-1 envelope requires expression of the human allele of the coreceptor for productive infection of these cells. These studies suggest that there are interactions among the coreceptor, the viral envelope, and another viral gene product that govern postentry steps of virus replication. These data are consistent with the hypothesis that such interactions may be required for translocation of the virus core to the nucleus. Moreover, the differential abilities of SIV and HIV-1 to function in these processes with heterologous primate coreceptors may have implications for cross-species transmission.

Chackerian, B; Long, E M; Luciw, P A; Overbaugh, J

1997-01-01

349

5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis  

PubMed Central

The steroid androst-5-ene-3ß,17ß-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-?B (NF?B)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not well understood. The aim of this study was to investigate the mechanisms of action of 5-AED administered subcutaneously (s.c.) to mice 24 h before total body ?- or X-irradiation (TBI). We used neutralizing antibodies, flow cytometric functional assays of circulating innate immune cells, analysis of expression of genes related to cell cycle progression, DNA repair and apoptosis, and assessment of DNA strand breaks with halo-comet assays. Neutralization experiments indicated endogenous G-CSF but not IL-6 was involved in survival enhancement by 5-AED. In keeping with known effects of G-CSF on the innate immune system, s.c. 5-AED stimulated phagocytosis in circulating granulocytes and oxidative burst in monocytes. 5-AED induced expression of both bax and bcl-2 in irradiated animals. Cdkn1a and ddb1, but not gadd45a expression, were upregulated by 5-AED in irradiated mice. S.c. 5-AED administration caused decreased DNA strand breaks in splenocytes from irradiated mice. Our results suggest 5-AED survival enhancement is G-CSF-dependent, and that it stimulates innate immune cell function and reduces radiation-induced DNA damage via induction of genes that modulate cell cycle progression and apoptosis.

Grace, Marcy B.; Singh, Vijay K.; Rhee, Juong G.; Jackson, William E.; Kao, Tzu-Cheg; Whitnall, Mark H.

2012-01-01

350

Urinary loss of tricarboxylic Acid cycle intermediates as revealed by metabolomics studies: an underlying mechanism to reduce lipid accretion by whey protein ingestion?  

PubMed

Whey protein intake is associated with the modulation of energy metabolism and altered body composition both in human subjects and in animals, but the underlying mechanisms are not yet elucidated. We fed obesity-prone C57BL/6J mice high-fat diets with either casein (HF casein) or whey (HF whey) for 6 weeks. At equal energy intake and apparent fat and nitrogen digestibility, mice fed HF whey stored less energy as lipids, evident both as lower white adipose tissue mass and as reduced liver lipids, compared with HF-casein-fed mice. Explorative analyses of 48 h urine, both by (1)H NMR and LC-MS metabolomic platforms, demonstrated higher urinary excretion of tricarboxylic acid (TCA) cycle intermediates citric acid and succinic acid (identified by both platforms), and cis-aconitic acid and isocitric acid (identified by LC-MS platform) in the HF whey, relative to in the HF-casein-fed mice. Targeted LC-MS analyses revealed higher citric acid and cis-aconitic acid concentrations in fed state plasma, but not in liver of HF-whey-fed mice. We propose that enhanced urinary loss of TCA cycle metabolites drain available substrates for anabolic processes, such as lipogenesis, thereby leading to reduced lipid accretion in HF-whey-fed compared to HF-casein-fed mice. PMID:24702026

Lillefosse, Haldis H; Clausen, Morten R; Yde, Christian C; Ditlev, Ditte B; Zhang, Xumin; Du, Zhen-Yu; Bertram, Hanne C; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

2014-05-01

351

Seasonal Nitrogen Cycles on Pluto  

NASA Technical Reports Server (NTRS)

A thermal model, developed to predict seasonal nitrogen cycles on Triton, has been modified and applied to Pluto. The model is used to calculate the partitioning of nitrogen between surface frost deposits and the atmosphere, as a function of time for various sets of input parameters.

Hansen, C. J.; Paige, D. A.

1994-01-01

352

Proteomic analysis of the bacterial cell cycle  

PubMed Central

A global approach was used to analyze protein synthesis and stability during the cell cycle of the bacterium Caulobacter crescentus. Approximately one-fourth (979) of the estimated C. crescentus gene products were detected by two-dimensional gel electrophoresis, 144 of which showed differential cell cycle expression patterns. Eighty-one of these proteins were identified by mass spectrometry and were assigned to a wide variety of functional groups. Pattern analysis revealed that coexpression groups were functionally clustered. A total of 48 proteins were rapidly degraded in the course of one cell cycle. More than half of these unstable proteins were also found to be synthesized in a cell cycle-dependent manner, establishing a strong correlation between rapid protein turnover and the periodicity of the bacterial cell cycle. This is, to our knowledge, the first evidence for a global role of proteolysis in bacterial cell cycle control.

Grunenfelder, Bjorn; Rummel, Gabriele; Vohradsky, Jiri; Roder, Daniel; Langen, Hanno; Jenal, Urs

2001-01-01

353

Small central receiver Brayton cycle study  

NASA Astrophysics Data System (ADS)

The potential of small scale, central receiver Brayton cycle systems to provide simple, highly reliable, low-maintenance electrical generating systems was investigated. The objectives were to identify Brayton cycle configurations suited for high-reliability central receiver systems generating electricity in the 2- and 25-MW/sub e/ power ranges and to identify and recommend high-temperature receiver designs most appropriate to the preferred cycle configurations. The cycle configurations considered were open and closed cycles with and without regeneration and/or intercooling. The configurations were assessed in terms of required machine design modifications, component availability turbomachinery location, costs and performance. Design point performance was studied as a function of system pressure, turbine inlet temperature and receiver pressure loss. An open cycle regenerated and intercooled configuration was selected for the 25-MW/sub e/ plant size. At the 2-MW/sub e/ size, an open simple cycle was chosen.

1985-01-01

354

The Water Cycle  

NSDL National Science Digital Library

Students will understand and explain parts of the water cycle. First watch the video to get a background about the water cycle: water cycle video Draw and explain the water cycle in your own words (include the terms: evaporation, condensation, precipitation, at least 3 bodies of water, the sun). Before reading the experiment record your predictions: If you put a small amount of water ...

Amanda, Miss

2011-02-14

355

Using Phospholipids and Stable Carbon Isotopes to Assess Microbial Community Structures and Carbon Cycle Pathways in Kamchatka Hot Springs  

NASA Astrophysics Data System (ADS)

Phospholipid fatty acid (PLFA) and stable carbon isotopes were used to assess the microbial community structures in Kamchatka hot springs. Eighteen mats or surface sediments were collected from hot springs having temperatures of 31 to 91°C and pHs of 4.9 to 8.5. These samples were clearly separated into three groups according to the bacterial PLFA: 1) those dominated by terminally branched odd-numbered fatty acids, 2) those dominated by C18:1 and 3) those dominated by C20:1. With support from other minor PLFA components, group 2 may be used as biomarkers for Chloroflexales or other phototrophic bacteria and group 3 for Aquificales, respectively. Among the sampled hot springs, the Arkashin pool represents the simplest microbial structure with members of Aquificales being the dominant primary producers. On the other hand, the Zavarzin pool may represent the most heterogeneous pool that may include members of Chloroflexales and Aquificales as primary producers. Bacterial 16S rDNA clone libraries confirmed the presence of these microbial groups in the two pools. Results of stable carbon isotope fractionation between CO2 source, bulk biomass and total PLFA showed that primary producers in the Arkashin pool primarily used the reductive tricarboxylic acid (rTCA) cycle (e.g., members of Aquificales); whereas the Zavarzin pool may be a mixture of the 3-hydroxypropionate (3-HP) pathway (e.g. members of Chloroflexales) and the rTCA cycle. Bacterial contribution using the Calvin cycle was not significant and may be less important in Kamchatka hot springs.

Zhao, W.; Romanek, C. S.; Burgess, E. A.; Wiegel, J.; Mills, G.; Zhang, C. L.

2006-12-01

356

Disjoint Cycles from the de Bruijn Graph.  

National Technical Information Service (NTIS)

The purpose of this paper is to investigate the cycle sets of the deBruijn graph resulting from the output of a general feedback function. The distribution of possible cycle decompositions categorized by the weight of their truth tables and the number of ...

H. M. Fredricksen

1968-01-01

357

A functional calvin cycle is not indispensable for the light activation of C4 phosphoenolpyruvate carboxylase kinase and its target enzyme in the maize mutant bundle sheath defective2-mutable1  

PubMed

We used a pale-green maize (Zea mays L.) mutant that fails to accumulate ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) to test the working hypothesis that the regulatory phosphorylation of C4 phosphoenolpyruvate carboxylase (PEPC) by its Ca2+-insensitive protein-serine/threonine kinase (PEPC kinase) in the C4 mesophyll cytosol depends on cross-talk with a functional Calvin cycle in the bundle sheath. Wild-type (W22) and bundle sheath defective2-mutable1 (bsd2-m1) seeds were grown in a controlled environment chamber at 100 to 130 &mgr;mol m-2 s-1 photosynthetic photon flux density, and leaf tissue was harvested 11 d after sowing, following exposure to various light intensities. Immunoblot analysis showed no major difference in the amount of polypeptide present for several mesophyll- and bundle-sheath-specific photosynthetic enzymes apart from Rubisco, which was either completely absent or very much reduced in the mutant. Similarly, leaf net CO2-exchange analysis and in vitro radiometric Rubisco assays showed that no appreciable carbon fixation was occurring in the mutant. In contrast, the sensitivity of PEPC to malate inhibition in bsd2-m1 leaves decreased significantly with an increase in light intensity, and there was a concomitant increase in PEPC kinase activity, similar to that seen in wild-type leaf tissue. Thus, although bsd2-m1 mutant plants lack an operative Calvin cycle, light activation of PEPC kinase and its target enzyme are not grossly perturbed. PMID:9733538

Smith; Langdale; Chollet

1998-09-01

358

Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study.  

PubMed

The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells. PMID:24350892

Han, Sungwon; Auger, Christopher; Thomas, Sean C; Beites, Crestina L; Appanna, Vasu D

2014-02-01

359

Pain perception during menstrual cycle.  

PubMed

Sexual hormones influence complex brain function and pain perception. Many psychophysical studies attempted to establish pain perception changes across menstrual cycle in animal models and healthy women or those with chronic pain. General results are quite uncertain in regard to consistent menstrual-related fluctuations of pain perception. The few studies applying neurophysiological procedures to test pain-related changes during menstrual cycle suggested a fluctuation of central modulation of pain across phases, with a prevalence of excitatory versus inhibitory control in the premenstrual period, which may explain the cyclic worsening of many syndromes, such as migraine. Whatever is the relevance of menstrual cycle on individual painful symptoms, it should be accepted as one of the numerous factors influencing mechanisms of neuromodulation. PMID:21556710

de Tommaso, Marina

2011-10-01

360

Increased lysine production by flux coupling of the tricarboxylic acid cycle and the lysine biosynthetic pathway--metabolic engineering of the availability of succinyl-CoA in Corynebacterium glutamicum.  

PubMed

In this study, we demonstrate increased lysine production by flux coupling using the industrial work horse bacterium Corynebacterium glutamicum, which was mediated by the targeted interruption of the tricarboxylic acid (TCA) cycle at the level of succinyl-CoA synthetase. The succinylase branch of the lysine production pathway functions as the bridging reaction to convert succinyl-CoA to succinate in this aerobic bacterium. The mutant C. glutamicum ?sucCD showed a 60% increase in the yield of lysine when compared to the advanced lysine producer which was used as parent strain. This mutant was highly vital and exhibited only a slightly reduced specific growth rate. Metabolic flux analysis with (13)C isotope studies confirmed that the increase in lysine production was mediated by pathway coupling. The novel strain exhibited an exceptional flux profile, which was closer to the optimum performance predicted by in silico pathway analysis than to the large set of lysine-producing strains analyzed thus far. Fluxomics and transcriptomics were applied as further targets for next-level strain engineering to identify the back-up mechanisms that were activated upon deletion of the enzyme in the mutant strain. It seemed likely that the cells partly recruited the glyoxylate shunt as a by-pass route. Additionally, the ?-ketoglutarate decarboxylase pathway emerged as the potential compensation mechanism. This novel strategy appears equally promising for Escherichia coli, which is used in the industrial production of lysine, wherein this bacterium synthesizes lysine exclusively by succinyl-CoA activation of pathway intermediates. The channeling of a high flux pathway into a production pathway by pathway coupling is an interesting metabolic engineering strategy that can be explored to optimize bio-production in the future. PMID:22871505

Kind, Stefanie; Becker, Judith; Wittmann, Christoph

2013-01-01

361

Immunology and the menstrual cycle.  

PubMed

Sex and gender differences in disease prevalence, pathogenesis and modulation have been frequently reported. The menstrual cycle represents the opportunity to study the physiological effect of hormonal fluctuations in vivo on the immune function and chronic disease modulation. Reports on the effect of the cycle on immune cell numbers and activity fluctuations are scarce, but recent publications demonstrate an increasing interest in the subject. The menstrual cycle might affect immune cell numbers and modulate their activity throughout the 4-week cycle, as demonstrated in the case of regulatory T cells. The implications of these fluctuations are particularly relevant in the field of chronic diseases affecting women of reproductive age. In fact, baseline inflammation and immune cell activation in association with other mechanisms, such as regulation of receptor expression, modulation of muscular contraction and behavioral aspects might explain the menstrual-associated fluctuations described in chronic and acute diseases. In the following review the current knowledge about the modulatory effects of the menstrual cycle on both immune cells and systemic diseases, such as autoimmune diseases, asthma, diabetes, cardiac arrhythmia and schizophrenia, is reported. Most of these diseases display worsening of symptoms premenstrually or during menses due to physiologic effects on the target tissue mediated by progesterone and estrogen fluctuations and, thus, display paradigmatic changes potentially relevant to numerous other conditions. PMID:22155200

Oertelt-Prigione, Sabine

2012-05-01

362

What-a-cycle  

NSDL National Science Digital Library

In this activity, students act as water molecules and travel through parts of the water cycle (ocean, atmosphere, clouds, glaciers, snow, rivers, lakes, ground, aquifer), noting on a hydrological cycle diagram the pathway traveled.

Weather, Jetstream -.; Service, Noaa -.

363

Vuilleumier Cycle Cryogenic Refrigeration.  

National Technical Information Service (NTIS)

This report describes in detailed the Vuilleumier (V-M) refrigeration cycle and various ways it has been applied to produce cryogenic temperatures. It starts with the most theoretical model of the Vuilleumier cycle and gradually adds complicating factors ...

R. White

1976-01-01

364

Amazon Water Cycle Roleplay  

NSDL National Science Digital Library

In this creative roleplay activity, learners will explore the various processes of the water cycle using movement, sound, and props to aid in comprehension. Learners will understand that water changes forms throughout the water cycle, and that this cycle runs continuously throughout all the cycles at the same time. This standards-based lesson, which is great for the classroom, camps, or afterschool programs, includes roleplay cards and ideas for props.

Sciences, California A.

2008-01-01

365

Water Cycle Webquest  

NSDL National Science Digital Library

Students are introduced to the Global Precipitation Measurement (GPM) satellite mission and its role in studying the water cycle. This webquest provides links to eight websites, allowing middle school students to explore the water cycle and its impacts on Earth's weather and climate. Through online videos and articles, students follow a water molecule through the cycle, discover the connection between the water cycle and global water/heat distribution, examine the role of solar energy, and assess the importance of fresh water.

366

Discover the Water Cycle!  

NSDL National Science Digital Library

This interactive tour of the water cycle allows students to follow a water molecule from a home's plumbing system as it follows different routes through the hydrologic cycle. Students learn about how water is used, treated, and returned to the natural environment where it can cycle through liquid, solid, and gas phases.

367

Advanced thermochemical hydrogen cycles  

Microsoft Academic Search

The overall objective of this program is to contribute to the development of practical thermochemical cycles for the production of hydrogen from water. Specific goals are: investigate and evaluate the technical and economic viability of thermochemical cycles as an advanced technology for producing hydrogen from water; investigate and evaluate the engineering principles involved in interfacing individual thermochemical cycles with the

C. M. Hollabaugh; M. G. Bowman

1981-01-01

368

The Rock Cycle  

NSDL National Science Digital Library

Create a poster about the rock cycle! Directions: Make a poster about the rock cycle. (20 points) Include at least (1) large picture (15 points) on your poster complete with labels of every part (10 points). (15 points) Include at least three (3) facts about the rock cycle. (5 points each) (15 points) Write at least a three sentence summary of your poster ...

Walls, Mrs.

2011-01-30

369

Homomorphisms to oriented cycles  

Microsoft Academic Search

We discuss the existence of homomorphisms to oriented cycles and give, for a special class of cycles C, a characterization of those digraphs that admit a homomorphism to C. Our characterization can be used to prove the multiplicativity of these cycles, as well as the membership of the corresponding decision problem in the class NP\\\\coNP. We also mention a conjecture

Pavol Hell; Huishan Zhou; Xuding Zhu

1993-01-01

370

Flashlets: Carnot Cycle  

NSDL National Science Digital Library

This site shows the fundamentals of the Carnot Cycle through a Flash simulation. Using a Pressure vs Volume (PV) plot the user observes how the cycle is carried out by different types of compressions and expansions. The simulation also includes an engine, constituted of a piston and a rod, illustrating the various processes in a Carnot Cycle.

Fowler, Michael; Ching, Jacquie H.

2008-08-08

371

Why the Learning Cycle?  

ERIC Educational Resources Information Center

The learning cycle is a way to structure inquiry in school science and occurs in several sequential phases. A learning cycle moves children through a scientific investigation by having them first explore materials, then construct a concept, and finally apply or extend the concept to other situations. Why the learning cycle? Because it is a…

Marek, Edmund A.

2008-01-01

372

The microbial cell cycle  

SciTech Connect

This book concentrates on the major problems of cell cycle control in microorganisms. A wide variety of microorganisms, ranging from bacteria and yeasts to hyphal fungi, algae, and ciliates are analyzed, with emphasis on the basic similarities among the organisms. Different ways of looking at cell cycle control which emphasize aspects of the problem such as circadian rhythms, limit cycle oscillators, and cell size models, are considered. New approaches such as the study of cell cycle mutants, and cloning of cell cycle control genes are also presented.

Nurse, P.; Streiblova, E.

1984-01-01

373

Pravastatin improves function in hibernating myocardium by mobilizing CD133+ and cKit+ bone marrow progenitor cells and promoting myocytes to reenter the growth phase of the cardiac cell cycle.  

PubMed

3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors have been reported to increase circulating bone marrow progenitor cells and variably improve global function in heart failure. The potential role of improved perfusion versus direct effects of statins on cardiac myocytes has not been established. We chronically instrumented swine with a left anterior descending artery (LAD) stenosis to produce chronic hibernating myocardium with regional contractile dysfunction in the absence of heart failure. Hemodynamics, function, perfusion, and histopathology were assessed in pigs treated for 5 weeks with pravastatin (n=12) versus untreated controls (n=10). Regional LAD wall thickening was depressed under baseline conditions (LAD 3.7+/-0.3 versus 6.6+/-0.3 in remote regions, P<0.01). It remained unchanged in untreated animals but increased from 3.8+/-0.6 to 5.2+/-0.5 mm after pravastatin (P<0.01). There was no increase in myocardial perfusion at rest or during vasodilation. Pravastatin mobilized circulating CD133(+)/cKit(+) bone marrow progenitor cells and increased myocardial tissue levels (LAD CD133(+) cells from 140+/-33 to 884+/-167 cells/10(6) myocyte nuclei and cKit(+) cells from 223+/-49 to 953+/-123 cells/10(6) myocyte nuclei). Pravastatin increased myocytes in mitosis (phospho-histone-H3; 9+/-5 to 43+/-7 nuclei/10(6) myocyte nuclei, P<0.05) and the growth phase of the cell cycle (Ki67; 410+/-82 to 1261+/-235 nuclei/10(6) myocyte nuclei, P<0.05) in diseased but not normal hearts. As a result, pravastatin increased LAD myocyte nuclear density from 830+/-41 to 1027+/-55 nuclei/mm(2) (P<0.05). These data indicate that, in the absence of impaired endothelial function and heart failure, dysfunctional hibernating myocardium improves after pravastatin. This effect is independent of myocardial perfusion and related to mobilization of CD133(+)/cKit(+) bone marrow progenitor cells which stimulate myocyte proliferation resulting in quantitative increases in myocyte nuclear density. PMID:19096024

Suzuki, Gen; Iyer, Vijay; Cimato, Thomas; Canty, John M

2009-01-30

374

Limit cycles and conformal invariance  

NASA Astrophysics Data System (ADS)

There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cyclic" CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.

Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

2013-01-01

375

Web-o-Cycles  

NSDL National Science Digital Library

Called the "Web-o-Cycles," groups of students are each assigned a different matter cycle to become deeply familiar with not only the internal components and interactions, but also possible connections to other cycles. For example, volcanic activity in the rock cycle also discharges sulfur into the atmosphere, which turn interacts with the water cycle in cloud formation. Connections such as these are made between posters of the cycles using colored yard, hooked on the appropriate nodes on each cycle and labeled by the nature of the interaction with the note cards hung on the yarn. In a short period of time, the classroom is a web of yarn, connecting each cycle to the others. The next element of this activity attempts to capture elements of complex Earth systems, especially the concepts of equilibrium, hysteresis, power law relationships, and sensitive dependence. All lines connecting the cycles are held taut, representing an equilibrium condition. Small shifts in one cycle are compensated for by consequent shifts in other cycles. Selecting one of the interconnecting strands, tension is in introduced, first in small pulls which accumulate to imbalance and shift the cycles slightly. A single large pull in one strand, to the point of breaking the yarn, causes some lines to slacken, perhaps to the point that they cannot be easily restored to tautness without dramatic shifts in the connected cycles. Re-tightening the connections causes a shift in the cycles, which takes place quickly and assumes a slightly different but at least familiar pattern. Having students then share their observations of the process of pattern description-imbalances-shifts-new equilibrium allows them to recognize the dynamic nature of Earth systems interactions as well as to seek deeper understanding of hidden elements within the Earth system. Materials needed: At least four posters depicting detailed graphical representations of matter cycles, such as water, carbon, rock, nitrogen, sulfur, phosphorous, mounted on cardboard or another rigid material. Students should have available to them information on each cycle, depicting relative volumes of material in each cycle phase, residence times of the material in those phases, and the processes that drive changes from one phase to another; At least one ball of yarn, in a different color, for each poster; Note cards on which students will write a description of the individual processes used to link cycles; Paper clips to hang the note cards on these connective strands.

Pyle, Eric

376

Expression and localization of ghrelin and its functional receptor in corpus luteum during different stages of estrous cycle and the modulatory role of ghrelin on progesterone production in cultured luteal cells in buffalo.  

PubMed

Evidence obtained during recent years provided has insight into the regulation of corpus luteum (CL) development, function, and regression by locally produced ghrelin. The present study was carried out to evaluate the expression and localization of ghrelin and its receptor (GHS-R1a) in bubaline CL during different stages of the estrous cycle and investigate the role of ghrelin on progesterone (P4) production along with messenger RNA (mRNA) expression of P4 synthesis intermediates. The mRNA and protein expression of ghrelin and GHS-R1a was significantly greater in mid- and late luteal phases. Both factors were localized in luteal cells, exclusively in the cytoplasm. Immunoreactivity of ghrelin and GHS-R1a was greater during mid- and late luteal phases. Luteal cells were cultured in vitro and treated with ghrelin each at 1, 10, and 100 ng/mL concentrations for 48 h after obtaining 75% to 80% confluence. At a dose of 1 ng/mL, there was no significant difference in P4 secretion between control and treatment group. At 10 and 100 ng/mL, there was a decrease (P < 0.05) in P4 concentration, cytochrome P45011A1 (CYP11A1), and 3-beta-hydroxysteroid dehydrogenase mRNA expression and localization. There was no difference in mRNA expression of steroidogenic acute regulatory protein between control and treatment group. In summary, the present study provided evidence that ghrelin and its receptor are expressed in bubaline CL and are localized exclusively in the cell cytoplasm and ghrelin has an inhibitory effect on P4 production in buffalo. PMID:24906925

Gupta, M; Dangi, S S; Chouhan, V S; Hyder, I; Babitha, V; Yadav, V P; Khan, F A; Sonwane, A; Singh, G; Das, G K; Mitra, A; Bag, S; Sarkar, M

2014-07-01

377

Use of S-PolKa Particles IDentification and TMI and MADRAS brightness temperatures to characterize the ice microphysics in rain systems as a function of their life cycle.  

NASA Astrophysics Data System (ADS)

In the framework of the French-Indian Megha-Tropiques Mission, a specific campaign was dedicated to ice microphysics studies during the CYNDIE-DYNAMO experiment. This contribution consisted in deploying the French Falcon 20 from mid-November to mid-December in Gan and perform about 40 hours of microphysics flights. The Falcon was equipped with a up- and downward looking W-Band Doppler Radar (RASTA) and a series of microphysics probes in order to characterize the ice particles in terms of density. This information is of dramatic importance to the microwave-based rain retrieval algorithms and more specifically the operational algorithm used in Megha-Tropiques known as BRAIN (Viltard et al 2006, Viltard et al 2012). This algorithm uses a retrieval database to reduce the number of possible solutions to those actually physical. This requires the computation of microwave brightness temperatures through a radiative transfer model in which the ice microphysics properties are parameterized. This parametrization is key for all brightness temperature simulation above roughly 30 GHz and strongly affects the quality of the rain retrieval. For the limited number of cases when the Falcon flew, we have a rather detailed description of the ice microphysics properties but this happens to be insufficient to build a robust statistics of the ice as a function of rain system life cycle. Hence the use of particles identification (PID) obtained from the ground-based polarimetric data from NCAR SPol-Ka. This dataset covers almost 5 month within a 200 km radius centered on Gan. We will briefly present our contribution in the CYNDIE-DYNAMO campaign and interpret in terms of microphysical properties the comparisons between these PIDs and the brightness temperatures measured by two passive microwave radiometers: TMI on TRMM and MADRAS on Megha-Tropiques.

Martini, Audrey; Viltard, Nicolas

2013-04-01

378

VISION - Verifiable Fuel Cycle Simulation of Nuclear Fuel Cycle Dynamics  

SciTech Connect

The U.S. DOE Advanced Fuel Cycle Initiative’s (AFCI) fundamental objective is to provide technology options that - if implemented - would enable long-term growth of nuclear power while improving sustainability and energy security. The AFCI organization structure consists of four areas; Systems Analysis, Fuels, Separations and Transmutations. The Systems Analysis Working Group is tasked with bridging the program technical areas and providing the models, tools, and analyses required to assess the feasibility of design and deployment options and inform key decision makers. An integral part of the Systems Analysis tool set is the development of a system level model that can be used to examine the implications of the different mixes of reactors, implications of fuel reprocessing, impact of deployment technologies, as well as potential "exit" or "off ramp" approaches to phase out technologies, waste management issues and long-term repository needs. The Verifiable Fuel Cycle Simulation Model (VISION) is a computer-based simulation model that allows performing dynamic simulations of fuel cycles to quantify infrastructure requirements and identify key trade-offs between alternatives. It is based on the current AFCI system analysis tool "DYMOND-US" functionalities in addition to economics, isotopic decay, and other new functionalities. VISION is intended to serve as a broad systems analysis and study tool applicable to work conducted as part of the AFCI and Generation IV reactor development studies.

Steven J. Piet; A. M. Yacout; J. J. Jacobson; C. Laws; G. E. Matthern; D. E. Shropshire

2006-02-01

379

Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo 31P nuclear magnetic resonance and electron paramagnetic resonance spectroscopy  

PubMed Central

Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy to noninvasively measure high-energy phosphate levels; mitochondrial aconitase activity measurements that directly correlate with TCA cycle flux, as measured by gas chromatography mass spectrometry (GC-MS); and electron paramagnetic resonance (EPR) to assess oxidative stress. At 6 h postburn, the oxidative ATP synthesis rate was increased 5-fold in burned mice given a single dose of SS-31 relative to untreated burned mice (P=0.002). Furthermore, SS-31 administration in burned animals decreased mitochondrial aconitase activity back to control levels. EPR revealed a recovery in redox status of the SS-31-treated burn group compared to the untreated burn group (P<0.05). Our multidisciplinary convergent results suggest that SS-31 promotes recovery of mitochondrial function after burn injury by increasing ATP synthesis rate, improving mitochondrial redox status, and restoring mitochondrial coupling. These findings suggest use of noninvasive in vivo NMR and complementary EPR offers an approach to monitor the effectiveness of mitochondrial protective agents in alleviating burn injury symptoms.—Righi, V., Constantinou, C., Mintzopoulos, D., Khan, N., Mupparaju, S. P., Rahme, L. G., Swartz, H. M., Szeto, H. H., Tompkins, R. G., and Tzika, A. A. Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo 31P nuclear magnetic resonance and electron paramagnetic resonance spectroscopy.

Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Khan, Nadeem; Mupparaju, S. P.; Rahme, Laurence G.; Swartz, Harold M.; Szeto, Hazel H.; Tompkins, Ronald G.; Tzika, A. Aria

2013-01-01

380

The adipocyte life cycle hypothesis.  

PubMed

The adipocyte life cycle hypothesis states that the metabolic properties of an adipocyte vary predictably during its life cycle: that as an adipocyte matures, it accumulates triacylglycerol (triglyceride) and becomes larger; that the rates of triacylglycerol synthesis and lipolysis are matched within adipocytes and that larger adipocytes, in general, have greater rates of triacylglycerol synthesis and, concurrently, greater rates of lipolysis and, therefore, larger adipocytes have greater rates of transmembrane fatty acid flux; and that the secretion of cytokines can also be related to adipocyte size with larger adipocytes having a more unfavourable profile of cytokine secretion than smaller adipocytes. Adipocyte location is an important modifier of this relationship and the favoured sites of adipocyte proliferation are a function of gender and the position within the life cycle of the organism at which proliferation occurs. The adipocyte life cycle hypothesis posits that the metabolic consequences of obesity depend on whether expansion of adipose tissue is achieved primarily by an increase in adipocyte number or adipocyte size. This hypothesis may explain a variety of previously unanswered clinical puzzles such as the vulnerability of many peoples from South East Asia to the adverse metabolic consequences of obesity. PMID:16336200

Smith, Jessica; Al-Amri, Maha; Dorairaj, Prabhakaran; Sniderman, Allan

2006-01-01

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