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Sample records for additional important role

  1. Deciphering the roles of multiple additives in organocatalyzed Michael additions.

    PubMed

    Günler, Z Inci; Companyó, Xavier; Alfonso, Ignacio; Burés, Jordi; Jimeno, Ciril; Pericàs, Miquel A

    2016-05-21

    The synergistic effects of multiple additives (water and acetic acid) on the asymmetric Michael addition of acetone to nitrostyrene catalyzed by primary amine-thioureas (PAT) were precisely determined. Acetic acid facilitates hydrolysis of the imine intermediates, thus leading to catalytic behavior, and minimizes the formation of the double addition side product. In contrast, water slows down the reaction but minimizes catalyst deactivation, eventually leading to higher final yields. PMID:27128165

  2. The Importance of Carbon Fiber to Polymer Additive Manufacturing

    SciTech Connect

    Love, Lonnie J; Kunc, Vlastimil; Rios, Orlando; Duty, Chad E; Post, Brian K; Blue, Craig A

    2014-01-01

    Additive manufacturing holds tremendous promise in terms of revolutionizing manufacturing. However, fundamental hurdles limit mass adoption of the technology. First, production rates are extremely low. Second, the physical size of parts is generally small, less than a cubic foot. Third, while there is much excitement about metal additive manufacturing, the major growth area is in polymer additive manufacturing systems. Unfortunately, the mechanical properties of the polymer parts are poor, limiting the potential for direct part replacement. To address this issue, we describe three benefits of blending carbon fiber with polymer additive manufacturing. First, development of carbon fiber reinforced polymers for additive manufacturing achieves specific strengths approaching aerospace quality aluminum. Second, carbon fiber radically changes the behavior of the material during deposition, enabling large scale, out-of-the-oven, high deposition rate manufacturing. Finally, carbon fiber technology and additive manufacturing complement each other. Merging the two manufacturing processes enables the construction of complex components that would not be possible otherwise.

  3. Curriculum change: the importance of team role.

    PubMed

    Broomfield, D; Bligh, J

    1997-03-01

    This paper describes a study examining aspects of team role in the management of curriculum change. The Belbin Team Role Self-Perception Inventory was completed by 25 members (83%) of a faculty curriculum development team. Overall the group showed a preference for the implementer and shaper roles, whilst the completer-finisher role was relatively weakly represented, ranking fifth out of eight possible roles. Older and more senior team members favoured the co-ordinator role, whilst younger and more junior members favoured the team-worker and completer-finisher roles. Some implications of these findings are discussed in the light of the current trend for widespread change in undergraduate medical curricula and the challenges faced by medical schools in a resource constrained environment. PMID:9231114

  4. Roles for RNA in Telomerase Nucleotide and Repeat Addition Processivity

    PubMed Central

    Lai, Cary K.; Miller, Michael C.; Collins, Kathleen

    2010-01-01

    Summary Telomerase is a ribonucleoprotein reverse transcriptase with two subunits critical for catalytic activity, the protein telomerase reverse transcriptase (TERT) and telomerase RNA. In this study, we establish additional roles of the telomerase RNA subunit by demonstrating that RNA motifs stimulate the processivity of nucleotide and repeat addition. These functions are both functionally and physically separable from the roles of other RNA motifs in establishing a properly defined template. Binding of Tetrahymena telomerase RNA stem IV to TERT enhances nucleotide addition processivity, while a cooperation of the RNA pseudoknot and stem IV promotes repeat addition processivity. The low processivity of DNA synthesis by telomerase ribonucleoproteins lacking the pseudoknot and/or stem IV can be rescued by addition of the deleted region in trans. These findings demonstrate RNA elements with roles in telomerase elongation processivity that are distinct from RNA elements that specify the internal template. PMID:12820978

  5. Roles of additives and surface control in slurry atomization

    SciTech Connect

    Tsai, S.C.

    1992-01-01

    This project studies the rheology and airblast atomization of micronized coal slurries. Its major objectives are (1) to promote further understanding of the mechanisms and the roles of additives in airblast atomization of coal water slurry (CWS), and (2) to investigate the impacts of coal particle surface properties and interparticle forces on CWS rheology. We have found that the flow behavior index (n) of a suspension (or slurry) is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The interparticle attraction, measured by the Hamaker constant scaled to the thermal energy at 25[degrees]C (A/kT), causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior (n< 1). At a constant particle volume fraction and surface charge density (qualitatively measured by the zeta potential in deionized water), n decreases linearly as A/kT increases. The relative viscosity of the pseudoplastic suspension with respect to that of the suspending liquid is found to be independent of particle density and correlate well with the particle Peclet number which equals the particle diffusional relaxation time multiplied by shear rate. Specifically, the relative viscosities of the pseudoplastic glycerol/water coal slurry and the ethylene glycol/glycerol sand slurry, at same volume fractions as well as similar particle size distributions and liquid viscosities, as functions of the particle Peclet number fall along the same line.

  6. Macitentan: An important addition to the treatment of pulmonary arterial hypertension

    PubMed Central

    Khadka, Anjan; Singh Brashier, Dick B; Tejus, Anantharamu; Sharma, Ashok Kumar

    2015-01-01

    Macitentan is an orphan drug for the treatment of pulmonary arterial hypertension (PAH). Endothelin-1 (ET-1) plays a critical role of pathophysiology of PAH. Macitentan, a new dual endothelin receptor antagonist, has reportedly improved prognosis of PAH patients by delaying the progression of disease. It prevents the binding of ET-1 to both endothelin A (ETA) and endothelin B (ETB) receptors. Macitentan displays higher efficacy, lesser adverse effects and drug interactions. It has completed phase III trials in 2012 for treatment of PAH and has been tried for ischemic digital ulcers in systemic sclerosis, recurrent glioblastoma and combination with chemotherapeutic agents against various cancers. Safety data for macitentan were obtained primarily from a placebo-controlled clinical study in 742 patients with PAH. The Food and Drug Administration (FDA) approved the drug on 13 October 2013. It is an important addition to long-term treatment of PAH. PMID:25709357

  7. Coaching Teachers: An Important Principal Role. Research into Practice

    ERIC Educational Resources Information Center

    Williamson, Ronald

    2012-01-01

    A principal's most important role is instructional leader. There is a growing recognition of the importance of working with teachers, serving as a mentor and coach. Coaching has emerged as one of the more effective professional development options for adult learners. It is an important tool because it is an investment in human capital and in the…

  8. New and important roles for DMSP in marine microbial communities

    NASA Astrophysics Data System (ADS)

    Kiene, R. P.; Linn, L. J.; Bruton, J. A.

    2000-08-01

    The algal osmolyte dimethylsulfoniopropionate (DMSP) is recognised as the major precursor of marine dimethylsulfide (DMS), a volatile sulfur compound that affects atmospheric chemistry and global climate. Recent studies, using 35S-DMSP tracer techniques, suggest that DMSP may play additional very important roles in the microbial ecology and biogeochemistry of the surface ocean. DMSP may serve as an intracellular osmolyte in bacteria that take up phytoplankton-derived DMSP from seawater. In addition, DMSP appears to support from 1 to 13% of the bacterial carbon demand in surface waters, making it one of the most significant single substrates for bacterioplankton so far identified. Furthermore, the sulfur from DMSP is efficiently incorporated into bacterial proteins (mostly into methionine) and DMSP appears to be a major source of sulfur for marine bacterioplankton. Assimilatory metabolism of DMSP is via methanethiol (MeSH) that is produced by a demethylation/demethiolation pathway which dominates DMSP degradation in situ. Based on the linkage between assimilatory metabolism of DMSP and bacterial growth, we offer a hypothesis whereby DMSP availability to bacteria controls the production of DMS by the competing DMSP lyase pathway. Also linked with the assimilatory metabolism of DMSP is the production of excess MeSH which, if not assimilated into protein, reacts to form dissolved non-volatile compounds. These include sulfate and DOM-metal-MeSH complexes, both of which represent major short-term end-products of DMSP degradation. Because production rates of MeSH in seawater are high (3-90 nM d -1), reaction of MeSH with trace metals could affect metal availability and chemistry in seawater. Overall, results of recent studies provide evidence that DMSP plays important roles in the carbon, sulfur and perhaps metal and DOM cycles in marine microbial communities. These findings, coupled with the fact that the small fraction of DMSP converted to DMS may influence atmospheric

  9. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE...

  10. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS,...

  11. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS,...

  12. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS,...

  13. 27 CFR 479.83 - Transfer tax in addition to import duty.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Transfer tax in addition to import duty. 479.83 Section 479.83 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE...

  14. Understanding composite explosive energetics: I, The role of metallic additives

    SciTech Connect

    Tao, W.C.; Tarver, C.M.; Breithaupt, D.R.; McGuire, R.R.; Ornellas, D.L.

    1990-01-01

    Composite explosives (CE) have found major applications in air blast, cratering, fragmentation, underwater applications, and other commercial and military systems in which prompt delivery of the available energy is not a primary requirement. In direct metal acceleration applications, composite explosives have not generally been effective because their potential energy is transformed to kinetic energy over time periods extending to tens of microseconds. We are interested in defining the rate determining steps and understanding the chemical interactions between different components in the composite explosive formulation in order to determine the partitioning of the available energy. In this study, we investigate the role of the metallic additive in a bicomponent composite explosive consisting of PETN and aluminum. Of specific interests are the early time performance of and the extent of aluminum reaction in the composite formulation. For formulations loaded with 5 wt% and 10 wt% of 5 micron spherical aluminum, we found that 100% of the aluminum reacted within the first microsecond of volume expansion. The extent of aluminum reaction with the PETN detonation products is reduced to about 65% for composite formulations loaded with 20 wt% aluminum. It is evident from the results of a series of scaling experiments that the detonation behavior of the PETN-aluminum bicomponent composite explosive is nonideal. 6 refs., 11 figs., 2 tabs.

  15. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  16. The Role of Additional Pulses in Electropermeabilization Protocols

    PubMed Central

    Suárez, Cecilia; Soba, Alejandro; Maglietti, Felipe; Olaiz, Nahuel; Marshall, Guillermo

    2014-01-01

    Electropermeabilization (EP) based protocols such as those applied in medicine, food processing or environmental management, are well established and widely used. The applied voltage, as well as tissue electric conductivity, are of utmost importance for assessing final electropermeabilized area and thus EP effectiveness. Experimental results from literature report that, under certain EP protocols, consecutive pulses increase tissue electric conductivity and even the permeabilization amount. Here we introduce a theoretical model that takes into account this effect in the application of an EP-based protocol, and its validation with experimental measurements. The theoretical model describes the electric field distribution by a nonlinear Laplace equation with a variable conductivity coefficient depending on the electric field, the temperature and the quantity of pulses, and the Penne's Bioheat equation for temperature variations. In the experiments, a vegetable tissue model (potato slice) is used for measuring electric currents and tissue electropermeabilized area in different EP protocols. Experimental measurements show that, during sequential pulses and keeping constant the applied voltage, the electric current density and the blackened (electropermeabilized) area increase. This behavior can only be attributed to a rise in the electric conductivity due to a higher number of pulses. Accordingly, we present a theoretical modeling of an EP protocol that predicts correctly the increment in the electric current density observed experimentally during the addition of pulses. The model also demonstrates that the electric current increase is due to a rise in the electric conductivity, in turn induced by temperature and pulse number, with no significant changes in the electric field distribution. The EP model introduced, based on a novel formulation of the electric conductivity, leads to a more realistic description of the EP phenomenon, hopefully providing more accurate

  17. The role of additional pulses in electropermeabilization protocols.

    PubMed

    Suárez, Cecilia; Soba, Alejandro; Maglietti, Felipe; Olaiz, Nahuel; Marshall, Guillermo

    2014-01-01

    Electropermeabilization (EP) based protocols such as those applied in medicine, food processing or environmental management, are well established and widely used. The applied voltage, as well as tissue electric conductivity, are of utmost importance for assessing final electropermeabilized area and thus EP effectiveness. Experimental results from literature report that, under certain EP protocols, consecutive pulses increase tissue electric conductivity and even the permeabilization amount. Here we introduce a theoretical model that takes into account this effect in the application of an EP-based protocol, and its validation with experimental measurements. The theoretical model describes the electric field distribution by a nonlinear Laplace equation with a variable conductivity coefficient depending on the electric field, the temperature and the quantity of pulses, and the Penne's Bioheat equation for temperature variations. In the experiments, a vegetable tissue model (potato slice) is used for measuring electric currents and tissue electropermeabilized area in different EP protocols. Experimental measurements show that, during sequential pulses and keeping constant the applied voltage, the electric current density and the blackened (electropermeabilized) area increase. This behavior can only be attributed to a rise in the electric conductivity due to a higher number of pulses. Accordingly, we present a theoretical modeling of an EP protocol that predicts correctly the increment in the electric current density observed experimentally during the addition of pulses. The model also demonstrates that the electric current increase is due to a rise in the electric conductivity, in turn induced by temperature and pulse number, with no significant changes in the electric field distribution. The EP model introduced, based on a novel formulation of the electric conductivity, leads to a more realistic description of the EP phenomenon, hopefully providing more accurate

  18. Role of membrane contact sites in protein import into mitochondria

    PubMed Central

    Horvath, Susanne E; Rampelt, Heike; Oeljeklaus, Silke; Warscheid, Bettina; van der Laan, Martin; Pfanner, Nikolaus

    2015-01-01

    Mitochondria import more than 1,000 different proteins from the cytosol. The proteins are synthesized as precursors on cytosolic ribosomes and are translocated by protein transport machineries of the mitochondrial membranes. Five main pathways for protein import into mitochondria have been identified. Most pathways use the translocase of the outer mitochondrial membrane (TOM) as the entry gate into mitochondria. Depending on specific signals contained in the precursors, the proteins are subsequently transferred to different intramitochondrial translocases. In this article, we discuss the connection between protein import and mitochondrial membrane architecture. Mitochondria possess two membranes. It is a long-standing question how contact sites between outer and inner membranes are formed and which role the contact sites play in the translocation of precursor proteins. A major translocation contact site is formed between the TOM complex and the presequence translocase of the inner membrane (TIM23 complex), promoting transfer of presequence-carrying preproteins to the mitochondrial inner membrane and matrix. Recent findings led to the identification of contact sites that involve the mitochondrial contact site and cristae organizing system (MICOS) of the inner membrane. MICOS plays a dual role. It is crucial for maintaining the inner membrane cristae architecture and forms contacts sites to the outer membrane that promote translocation of precursor proteins into the intermembrane space and outer membrane of mitochondria. The view is emerging that the mitochondrial protein translocases do not function as independent units, but are embedded in a network of interactions with machineries that control mitochondrial activity and architecture. PMID:25514890

  19. Perceived Role Legitimacy and Role Importance of Australian School Staff in Addressing Student Cannabis Use

    ERIC Educational Resources Information Center

    Gates, Peter J.; Norberg, Melissa M.; Dillon, Paul; Manocha, Ramesh

    2013-01-01

    The high prevalence of cannabis use by Australian secondary school students makes schools an ideal setting for the delivery of substance use prevention programs. Although efficacious school-based cannabis prevention programs exist, there is scant research investigating the perceived role legitimacy and role importance of school staff. As such,…

  20. The Role of Drugs, Diet, and Food Additives in Hyperactivity.

    ERIC Educational Resources Information Center

    Harshbarger, Mary E.

    A variety of causes have been suggested for hyperactivity: anoxia and other adverse birth conditions, genetic factors, delayed maturation, maternal smoking and drinking during pregnancy, interaction of temperament and environment, lead poisoning, radiation stress, allergy and food additives, and deprivation of required stimulation. Treatments…

  1. Children's Additive Concepts: Promoting Understanding and the Role of Inhibition

    ERIC Educational Resources Information Center

    Robinson, Katherine M.; Dube, Adam K.

    2013-01-01

    This study investigated the promotion of children's understanding and acquisition of arithmetic concepts and the effects of inhibitory skills. Children in Grades 3, 4, and 5 solved two sets of three-term addition and subtraction problems (e.g., 3 + 24 - 24, 3 + 24 - 22) and completed an inhibition task. Half of the participants received a…

  2. Recognition of additional roles for immunoglobulin domains in immune function

    PubMed Central

    Cannon, John P.; Dishaw, Larry J.; Haire, Robert N.; Litman, Ronda T.; Ostrov, David A.; Litman, Gary W.

    2010-01-01

    Characterization of immune receptors found in phylogenetically disparate species at the genetic, structural and functional levels has provided unique insight into the evolutionary acquisition of immune function. The roles of variable- and intermediate-type immunoglobulin (Ig) domains in direct recognition of ligands and other functions are far wider than previously anticipated. Common mechanisms of multigene family diversification and expansion as well as unique adaptations that relate to function continue to provide unique insight into the numerous patterns, processes and complex interactions that regulate the host response to infectious challenge. PMID:20004115

  3. [Roles of additives and surface control in slurry atomization

    SciTech Connect

    Tsai, S.C.

    1992-06-01

    As reported in the quarterly report of March of 1992, the relative viscosity of a Newtonian Coal Water Slurry (CWS) in the presence of an anionic polymeric dispersant is an order of magnitude higher than the prediction of the well established Krieger-Dougherty Equation which describes the relative viscosity of a non-aggregated Newtonian suspension as a function of particle volume fraction. Note that the anionic dispersant is used in such a quantity that the resulting interparticle electrostatic repulsion counter-balances the interparticle van der Waals attraction. Investigation continues to determine the mechanisms of such excess energy dissipation under shear. New experimental results are presented in this report to verify the role of the anionic polymeric dispersant in such excess energy dissipation of CWS.

  4. Hyponatraemia in imported malaria: the pathophysiological role of vasopressin

    PubMed Central

    2012-01-01

    Background In the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP) release is unknown; the trigger for inappropriate AVP release is also unknown. Methods Serum copeptin, a stable and sensitive marker for AVP release, was analysed in a large cohort of patients with imported malaria (204 patients) and in a small prospective substudy (23 patients) in which urine sodium and osmolality were also available. Hyponatraemia was classified as mild (serum sodium 131-134 mmol/l) and moderate-to-severe (< 131 mmol/l). Results Serum copeptin on admission was higher in patients with moderate-to-severe hyponatraemia (median 18.5 pmol/L) compared with normonatraemic patients (12.7 pmol/L, p < 0.05). Despite prompt fluid resuscitation, the time to normalization of serum sodium was longer in patients with moderate-to-severe hyponatraemia (median 2.9 days) than in patients with mild hyponatraemia (median 1.7 days, p < 0.001). A poor correlation was found between serum sodium and copeptin levels on admission (rs = -0.17, p = 0.017). Stronger correlations were identified between serum C-reactive protein and copeptin (rs = -0.36, p < 0.0001) and between serum C-reactive protein and sodium (rs = 0.33, p < 0.0001). Data from the sub-study suggested inappropriate AVP release in seven of 13 hyponatraemic malaria patients; these patients had significantly higher body temperatures on admission. Conclusions In hyponatraemic patients with imported malaria, AVP release was uniformly increased and was either appropriate or inappropriate. Although the exact trigger for inappropriate AVP release remains unknown, the higher body temperatures, correlations with C-reactive protein and long normalization times of serum sodium, suggest an important role of the host inflammatory response to the invading malaria parasite. PMID:22280539

  5. Copy number variation plays an important role in clinical epilepsy

    PubMed Central

    Olson, Heather; Shen, Yiping; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Schonwald, Alison; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Wu, Bai-Lin; Miller, David T.; Poduri, Annapurna

    2015-01-01

    Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. PMID:24811917

  6. Skin innervation: important roles during normal and pathological cutaneous repair.

    PubMed

    Laverdet, Betty; Danigo, Aurore; Girard, Dorothée; Magy, Laurent; Demiot, Claire; Desmoulière, Alexis

    2015-08-01

    The skin is a highly sensitive organ. It is densely innervated with different types of sensory nerve endings, which discriminate between pain, temperature and touch. Autonomic nerve fibres which completely derive from sympathetic (cholinergic) neurons are also present. During all the phases of skin wound healing (inflammatory, proliferative and remodelling phases), neuromediators are involved. Several clinical observations indicate that damage to the peripheral nervous system influences wound healing, resulting in chronic wounds within the affected area. Patients with cutaneous sensory defects due to lepromatous leprosy, spinal cord injury and diabetic neuropathy develop ulcers that fail to heal. In addition, numerous experimental observations suggest that neurogenic stimuli profoundly affect wound repair after injury and that delayed wound healing is observed in animal models after surgical resection of cutaneous nerves. All these observations clearly suggest that innervation and neuromediators play a major role in wound healing. Interactions between neuromediators and different skin cells are certainly crucial in the healing process and ultimately the restoration of pain, temperature, and touch perceptions is a major challenge to solve in order to improve patients' quality of life. PMID:25799052

  7. Roles of additives and surface control in slurry atomization

    SciTech Connect

    Tsai, S.C.

    1990-01-01

    This report focuses on the effects of interparticle forces on the rheology and airblast atomization of micronized coal water slurry (CWS). We found that the CWS flow behavior index is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The former intensifies as the Hamaker constant increases and the interparticle distance reduces while the latter increases as the particle surface charge density increases. The interparticle attraction causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior. In contrast, the interparticle repulsion prevents particle aggregation and thus leads to Newtonian behavior. Both atomized at low atomizing air pressures (less than 270 kPa) using twin-fluid jet atomizers of various distributor designs. We found that the atomized drop sizes of micronized coal water slurries substantially decrease as the atomizing air pressure exceeds a threshold value. The effects of coal volume fraction, coal particle surface charge, liquid composition and liquid viscosity on slurry atomization can be accounted for by their effects on slurry rheology. 26 refs.

  8. Role and Importance of IGF-1 in Traumatic Brain Injuries

    PubMed Central

    Mangiola, Annunziato; Vigo, Vera; Anile, Carmelo; De Bonis, Pasquale; Marziali, Giammaria; Lofrese, Giorgio

    2015-01-01

    It is increasingly affirmed that most of the long-term consequences of TBI are due to molecular and cellular changes occurring during the acute phase of the injury and which may, afterwards, persist or progress. Understanding how to prevent secondary damage and improve outcome in trauma patients, has been always a target of scientific interest. Plans of studies focused their attention on the posttraumatic neuroendocrine dysfunction in order to achieve a correlation between hormone blood level and TBI outcomes. The somatotropic axis (GH and IGF-1) seems to be the most affected, with different alterations between the acute and late phases. IGF-1 plays an important role in brain growth and development, and it is related to repair responses to damage for both the central and peripheral nervous system. The IGF-1 blood levels result prone to decrease during both the early and late phases after TBI. Despite this, experimental studies on animals have shown that the CNS responds to the injury upregulating the expression of IGF-1; thus it appears to be related to the secondary mechanisms of response to posttraumatic damage. We review the mechanisms involving IGF-1 in TBI, analyzing how its expression and metabolism may affect prognosis and outcome in head trauma patients. PMID:26417600

  9. Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma

    PubMed Central

    Rosas-Salazar, Christian; James, Kristina; Escobar, Gabriel; Gebretsadik, Tebeb; Li, Sherian Xu; Carroll, Kecia N.; Walsh, Eileen; Mitchel, Edward; Das, Suman; Kumar, Rajesh; Yu, Chang; Dupont, William D.; Hartert, Tina V.

    2016-01-01

    Background Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. Methods We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. Results Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal

  10. The Importance of Role Perceptions in the Student Teaching Triad

    ERIC Educational Resources Information Center

    Johnson, Ingrid L.; Napper-Owen, Gloria

    2011-01-01

    The purpose of this study was to examine the roles and role perceptions held by members of physical education student teaching triads while engaged in a seven-week elementary student teaching experience. It is believed that knowledge is created through group interactions (i.e., triad) in the environment, and therefore a social constructivist…

  11. Characteristics Students View as Important in Nurse Faculty Role Models.

    ERIC Educational Resources Information Center

    Cooper, Geneva

    Nursing students' views concerning the behavior of faculty role models were studied. The sample consisted of 75 senior-level baccalaureate nursing students, 69 females and 6 males. The theoretical framework for the research was role theory and Bandura's social learning and modeling theory. The Clinical Instructor Characteristics Ranking Scale…

  12. Learning to Solve Addition and Subtraction Word Problems in English as an Imported Language

    ERIC Educational Resources Information Center

    Verzosa, Debbie Bautista; Mulligan, Joanne

    2013-01-01

    This paper reports an intervention phase of a design study aimed to assist second-grade Filipino children in solving addition word problems in English, a language they primarily encounter only in school. With Filipino as the medium of instruction, an out-of-school pedagogical intervention providing linguistic and representational scaffolds was…

  13. 75 FR 29680 - Importation of Mexican Hass Avocados; Additional Shipping Options

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... specify that the boxes, bins, or crates would have to be safeguarded from insects by covering with a lid, insect-proof mesh, or by some other barrier that prevents insects from entering the boxes or bins. Those... provide an additional layer of protection against insects of concern. The regulations also contain...

  14. ASXL1 plays an important role in erythropoiesis

    PubMed Central

    Shi, Hui; Yamamoto, Shohei; Sheng, Mengyao; Bai, Jie; Zhang, Peng; Chen, Runze; Chen, Shi; Shi, Lihong; Abdel-Wahab, Omar; Xu, Mingjiang; Zhou, Yuan; Yang, Feng-Chun

    2016-01-01

    ASXL1 mutations are found in a spectrum of myeloid malignancies with poor prognosis. Recently, we reported that Asxl1+/− mice develop myelodysplastic syndrome (MDS) or MDS and myeloproliferative neoplasms (MPN) overlapping diseases (MDS/MPN). Although defective erythroid maturation and anemia are associated with the prognosis of patients with MDS or MDS/MPN, the role of ASXL1 in erythropoiesis remains unclear. Here, we showed that chronic myelomonocytic leukemia (CMML) patients with ASXL1 mutations exhibited more severe anemia with a significantly increased proportion of bone marrow (BM) early stage erythroblasts and reduced enucleated erythrocytes compared to CMML patients with WT ASXL1. Knockdown of ASXL1 in cord blood CD34+ cells reduced erythropoiesis and impaired erythrocyte enucleation. Consistently, the BM and spleens of VavCre+;Asxl1f/f (Asxl1∆/∆) mice had less numbers of erythroid progenitors than Asxl1f/f controls. Asxl1∆/∆ mice also had an increased percentage of erythroblasts and a reduced erythrocyte enucleation in their BM compared to littermate controls. Furthermore, Asxl1∆/∆ erythroblasts revealed altered expression of genes involved in erythroid development and homeostasis, which was associated with lower levels of H3K27me3 and H3K4me3. Our study unveils a key role for ASXL1 in erythropoiesis and indicates that ASXL1 loss hinders erythroid development/maturation, which could be of prognostic value for MDS/MPN patients. PMID:27352931

  15. ASXL1 plays an important role in erythropoiesis.

    PubMed

    Shi, Hui; Yamamoto, Shohei; Sheng, Mengyao; Bai, Jie; Zhang, Peng; Chen, Runze; Chen, Shi; Shi, Lihong; Abdel-Wahab, Omar; Xu, Mingjiang; Zhou, Yuan; Yang, Feng-Chun

    2016-01-01

    ASXL1 mutations are found in a spectrum of myeloid malignancies with poor prognosis. Recently, we reported that Asxl1(+/-) mice develop myelodysplastic syndrome (MDS) or MDS and myeloproliferative neoplasms (MPN) overlapping diseases (MDS/MPN). Although defective erythroid maturation and anemia are associated with the prognosis of patients with MDS or MDS/MPN, the role of ASXL1 in erythropoiesis remains unclear. Here, we showed that chronic myelomonocytic leukemia (CMML) patients with ASXL1 mutations exhibited more severe anemia with a significantly increased proportion of bone marrow (BM) early stage erythroblasts and reduced enucleated erythrocytes compared to CMML patients with WT ASXL1. Knockdown of ASXL1 in cord blood CD34(+) cells reduced erythropoiesis and impaired erythrocyte enucleation. Consistently, the BM and spleens of VavCre(+);Asxl1(f/f) (Asxl1(∆/∆)) mice had less numbers of erythroid progenitors than Asxl1(f/f) controls. Asxl1(∆/∆) mice also had an increased percentage of erythroblasts and a reduced erythrocyte enucleation in their BM compared to littermate controls. Furthermore, Asxl1(∆/∆) erythroblasts revealed altered expression of genes involved in erythroid development and homeostasis, which was associated with lower levels of H3K27me3 and H3K4me3. Our study unveils a key role for ASXL1 in erythropoiesis and indicates that ASXL1 loss hinders erythroid development/maturation, which could be of prognostic value for MDS/MPN patients. PMID:27352931

  16. Implications of Export/Import Reporting Requirements in the United States - International Atomic Energy Agency Safeguards Additional Protocol

    SciTech Connect

    Killinger, Mark H.; Benjamin, Eugene L.; McNair, Gary W.

    2001-02-20

    The United States has signed but not ratified the US/IAEA Safeguards Additional Protocol. If ratified, the Additional Protocol will require the US to report to the IAEA certain nuclear-related exports and imports to the IAEA. This document identifies and assesses the issues associated with the US making those reports. For example, some regulatory changes appear to be necessary. The document also attempts to predict the impact on the DOE Complex by assessing the historical flow of exports and imports that would be reportable if the Additional Protocol were in force.

  17. Medication Safety Systems and the Important Role of Pharmacists.

    PubMed

    Mansur, Jeannell M

    2016-03-01

    Preventable medication-related adverse events continue to occur in the healthcare setting. While the Institute of Medicine's To Err is Human, published in 2000, highlighted the prevalence of medical and medication-related errors in patient morbidity and mortality, there has not been significant documented progress in addressing system contributors to medication errors. The lack of progress may be related to the myriad of pharmaceutical options now available and the nuances of optimizing drug therapy to achieve desired outcomes and prevent undesirable outcomes. However, on a broader scale, there may be opportunities to focus on the design and performance of the many processes that are part of the medication system. Errors may occur in the storage, prescribing, transcription, preparation and dispensing, or administration and monitoring of medications. Each of these nodes of the medication system, with its many components, is prone to failure, resulting in harm to patients. The pharmacist is uniquely trained to be able to impact medication safety at the individual patient level through medication management skills that are part of the clinical pharmacist's role, but also to analyze the performance of medication processes and to lead redesign efforts to mitigate drug-related outcomes that may cause harm. One population that can benefit from a focus on medication safety through clinical pharmacy services and medication safety programs is the elderly, who are at risk for adverse drug events due to their many co-morbidities and the number of medications often used. This article describes the medication safety systems and provides a blueprint for creating a foundation for medication safety programs within healthcare organizations. The specific role of pharmacists and clinical pharmacy services in medication safety is also discussed here and in other articles in this Theme Issue. PMID:26932714

  18. The Important Role of Physics in Industry and Economic Development

    NASA Astrophysics Data System (ADS)

    Alvarado, Igor

    2012-10-01

    Good Physics requires good education. Good education translates into good Physics professionals. The process starts early with Science, Technology, Engineering and Mathematics (STEM) education programs for Middle and High-School students. Then it continues with competitive higher education programs (2 years and 4 years) at colleges and universities designed to satisfy the needs of industry and academia. The research work conducted by graduate students in Physics (and Engineering Physics) frequently translates into new discoveries and innovations that have direct impact in society (e.g. Proton Cancer Therapy). Some of the major and largest scientific experiments in the world today are physics-centered (e.g. Large Hadron Collider-LHC) that generate employment and business opportunities for thousands of scientists, academic research groups and companies from around the world. New superconducting magnets and advanced materials that have resulted from previous research in physics are commonly used in these extreme experiments. But not all physicists will end up working at these large high-energy physics experiments, universities or National Laboratories (e.g. Fermilab); industry requires new generations of (industrial) physicists in such sectors as semiconductor, energy, space, life sciences, defense and advanced manufacturing. This work presents an industry perspective about the role of Physics in economic development and the need for a collaborative Academic-Industry approach for a more effective translational research. A series of examples will be presented with emphasis in the measurement, control, diagnostics and computing capabilities needed to translate the science (physics) into innovations and practical solutions that can benefit society as a whole.

  19. PRKX, a Novel cAMP-Dependent Protein Kinase Member, Plays an Important Role in Development.

    PubMed

    Huang, Sizhou; Li, Qian; Alberts, Ian; Li, Xiaohong

    2016-03-01

    The human protein kinase X gene (PRKX) and cAMP-dependent protein kinase (PKA) are both c-AMP-dependent serine/threonine protein kinases within the protein kinase AGC subgroup. Of all the protein kinases in this group, PRKX is the least studied. PRKX has been isolated from patients with chondrodysplasia punctate and is involved in numerous processes, including sexual differentiation and fertilization, normal kidney development and autosomal dominant polycystic kidney disease (ADPKD), blood maturation, neural development, and angiogenesis in vitro. Although the role of PRKX in development and disease has been reported recently, the underlying mechanism of PRKX activity is largely unknown. In addition, based on the expression pattern of PRKX and the extensive role of PKA in disease and development, PRKX might have additional crucial functions that have not been addressed in the literature. In this review, we summarize the characteristics and developmental functions of PRKX that have been reported by recent studies. In particular, we elucidate the structural and functional differences between PRKX and PKA, as well as the possible roles of PRKX in development and related diseases. Finally, we propose future studies that could lead to important discoveries of more PRKX functions and the underlying mechanisms involved. PMID:26252946

  20. The role of imported water on urban water budgets in southern California

    NASA Astrophysics Data System (ADS)

    Manago, K. F.; Hogue, T. S.; Pataki, D. E.; Pincetl, S.

    2013-12-01

    The current study focuses on the development of historical water balances for urban watersheds in the southern California region. We undertake comparison for a range of development levels to provide insight on the role of imported water on spatial and temporal hydrologic cycling and regional change caused by increasing urbanization. Three adjacent watersheds were selected in the Los Angeles area for variability in land cover types (and data availability): Ballona Creek, a highly urbanized watershed (1938-2009), the Los Angeles River, a semi-urban watershed (1930-2009), and Malibu Creek, one of the more undeveloped watersheds in the area (1932-2009). The urban water balance is a modification of the original water balance where additional terms and alternative methods are used to account for anthropogenic inputs and effects such as imported water, irrigation, treated wastewater, and leaky pipes. A combination of USGS National Land Cover Database and population data are used as a proxy for long-term land cover, which is essential in estimating outdoor water use and evapotranspiration. Precipitation and temperature data are estimated from PRISM data and long-term discharge records are obtained from the Los Angeles Department of Public Works. Preliminary results show a trend of increasing evapotranspiration and imported outdoor water use for all three watersheds. Additionally, evapotranspiration and runoff increase with development intensity, where Ballona Creek has the highest rates and Malibu Creek has the lowest. Ballona Creek's runoff ratio shows the largest increase over time, frequently exceeding the theoretical limit during the most recent decade (2000-2009) which included several dry periods and extensive imported water use. Ongoing work includes future climate scenarios and the availability of local water resources in regional watersheds that are heavily dependent on imported water.

  1. Roles of additives and surface control in slurry atomization. Final project report

    SciTech Connect

    Tsai, S.C.

    1992-12-31

    This project studies the rheology and airblast atomization of micronized coal slurries. Its major objectives are (1) to promote further understanding of the mechanisms and the roles of additives in airblast atomization of coal water slurry (CWS), and (2) to investigate the impacts of coal particle surface properties and interparticle forces on CWS rheology. We have found that the flow behavior index (n) of a suspension (or slurry) is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The interparticle attraction, measured by the Hamaker constant scaled to the thermal energy at 25{degrees}C (A/kT), causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior (n< 1). At a constant particle volume fraction and surface charge density (qualitatively measured by the zeta potential in deionized water), n decreases linearly as A/kT increases. The relative viscosity of the pseudoplastic suspension with respect to that of the suspending liquid is found to be independent of particle density and correlate well with the particle Peclet number which equals the particle diffusional relaxation time multiplied by shear rate. Specifically, the relative viscosities of the pseudoplastic glycerol/water coal slurry and the ethylene glycol/glycerol sand slurry, at same volume fractions as well as similar particle size distributions and liquid viscosities, as functions of the particle Peclet number fall along the same line.

  2. TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts

    PubMed Central

    Woo, Jin Seok; Cho, Chung-Hyun; Kim, Do Han

    2010-01-01

    During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without α1SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in α1SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or α1SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca2+ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes. PMID:20644344

  3. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies

    PubMed Central

    Vally, H; Thompson, P

    2001-01-01

    flow (FEF25-75)) between wine sensitive and normal asthmatic subjects.
CONCLUSIONS—Only a small number of wine sensitive asthmatic patients responded to a single dose challenge with sulfited wine under laboratory conditions. This may suggest that the role of sulfites and/or wine in triggering asthmatic responses has been overestimated. Alternatively, cofactors or other components in wine may play an important role in wine induced asthma. Cumulative sulfite dose challenges did not detect an increased sensitivity to sulfite in wine sensitive asthmatics and an alternative approach to identifying sulfite/wine sensitive asthma may be required.

 PMID:11562514

  4. The Role of Imported Cases and Favorable Meteorological Conditions in the Onset of Dengue Epidemics

    PubMed Central

    Shang, Chuin-Shee; Wen, Tzai-Hung; Tsai, Kun-Hsien

    2010-01-01

    Background Travelers who acquire dengue infection are often routes for virus transmission to other regions. Nevertheless, the interplay between infected travelers, climate, vectors, and indigenous dengue incidence remains unclear. The role of foreign-origin cases on local dengue epidemics thus has been largely neglected by research. This study investigated the effect of both imported dengue and local meteorological factors on the occurrence of indigenous dengue in Taiwan. Methods and Principal Findings Using logistic and Poisson regression models, we analyzed bi-weekly, laboratory-confirmed dengue cases at their onset dates of illness from 1998 to 2007 to identify correlations between indigenous dengue and imported dengue cases (in the context of local meteorological factors) across different time lags. Our results revealed that the occurrence of indigenous dengue was significantly correlated with temporally-lagged cases of imported dengue (2–14 weeks), higher temperatures (6–14 weeks), and lower relative humidity (6–20 weeks). In addition, imported and indigenous dengue cases had a significant quantitative relationship in the onset of local epidemics. However, this relationship became less significant once indigenous epidemics progressed past the initial stage. Conclusions These findings imply that imported dengue cases are able to initiate indigenous epidemics when appropriate weather conditions are present. Early detection and case management of imported cases through rapid diagnosis may avert large-scale epidemics of dengue/dengue hemorrhagic fever. The deployment of an early-warning surveillance system, with the capacity to integrate meteorological data, will be an invaluable tool for successful prevention and control of dengue, particularly in non-endemic countries. PMID:20689820

  5. Versatile Role of Solvent Additive for Tailoring Morphology in Polymer Solar Cells for Efficient Charge Transport.

    PubMed

    Khatiwada, Devendra; Venkatesan, Swaminathan; Ngo, Evan C; Qiao, Qiquan

    2015-09-01

    In this work role of solvent additive namely 1,8 diiodoctane (DIO) on the nanoscale morphology and its relation with the charge transport of poly(diketopyrrolopyrrole-terthiophene) (PDPP3T):PCBM solar cells has been investigated. Addition of DIO led to enhanced structural ordering as observed from optical measurements. Photovoltaic devices processed with DIO additive showed improved efficiencies due to significant enhancement in short circuit current density. Atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM) images showed that DIO led to finer phase segregation that gave rise to better photovoltaic performance in additive processed active layers. Photoinduced current extraction by linearly increasing voltage (P-CELIV) measurements on PDPP3T:PCBM solar cells revealed higher mobility and extracted charge carrier density for DIO processed devices. PMID:26716280

  6. Role of additives in wood plastic composite of water soluble monomer

    NASA Astrophysics Data System (ADS)

    Ali, K. M. Idriss; Khan, Mubarak A.; Husain, M. M.

    1994-10-01

    Wood plastic composites are prepared under radiation of 60Co gamma source with simul, a low grade wood of Bangladesh using a water soluble monomer acrylamide (AM) mixed with a swelling solvent methanol, water or methanol/water (1:1) at different compositions in the presence of a number of additives and co-additives such as NVP ( N-vinylpyrrolidone), TPGDA (tripropylene glycol diacrylate), TMPTA (trimethylol propane triacrylate), sulfuric acid, urea and copper sulfate. Polymer loading (PL) and tensile strength (TS) of the composites are measured. The role of these additives on the composites is also discussed. It is observed that nitrogen-atom containing-materials like urea, NVP and AM produce composites with the highest mechanical strength, and incorporation of copper into this system provides additional property of protection and preservation of the composites against attacks by insects and microbes.

  7. Tailoring magnetic properties in arrays of pulse-electrodeposited Co nanowires: The role of Cu additive

    NASA Astrophysics Data System (ADS)

    Esmaeili, A.; Almasi Kashi, M.; Ramazani, A.; Montazer, A. H.

    2016-01-01

    In this study, we aim to report the role of Cu additive in arrays of pulse-electrodeposited Co nanowires (NWs) with diameters from 30 to 75 nm, embedded in porous aluminum oxide templates. This features the role of Cu additive in composition and crystalline characteristics as well as in the magnetic properties of Co NWs. Increasing the duration of off-time between pulses during the electrodeposition of Co NWs made it possible to increase the amount of Cu content, so that Co-rich CoCu NWs were obtained. The parallel coercivity and squareness values increased up to 1500 Oe and 0.8 for 30 nm diameter Co94Cu6 NWs, starting from 500 Oe and 0.3 for pure Co NWs. On the other hand, although there was a substantial difference between the crystalline characteristics of 75 nm diameter pure Co and CoCu NWs, no considerable change in their magnetic properties was observed using hysteresis loop measurements. In this respect, the first-order reversal curve (FORC) analysis revealed strong inter-wire magnetostatic interactions for the CoCu NWs. Moreover, we studied the effect of thermal annealing, which resulted in an increase in the coercivity of CoCu NWs with different diameters up to 15%. As a result, the addition of small amount of Cu provides an alternative approach to tailoring the magnetic properties of Co NWs.

  8. Role Modeling in Medical Education: The Importance of a Reflective Imitation

    PubMed Central

    2014-01-01

    The medical literature almost uniformly addresses the positive aspects of role modeling. Still, some authors have questioned its educational value, a disagreement that is probably due to differing definitions of role modeling. If defined as demonstration of skills, provision of feedback, and emulation of specific professional behaviors, then role modeling is an important component of clinical training. However, if it is defined as a learner’s unselective imitation of role models and uncritical adoption of the messages of the learning environment, then the benefits of role modeling should be weighed against its unintended harm. In this Perspective, the author argues that imitation of role models may initially help students adapt to the clinical environment. However, if sustained, imitation may perpetuate undesirable practices, such as doctor-centered patient interviewing, and unintended institutional norms, such as discrimination between private and public patients. The author suggests that the value of role modeling can be advanced not only by targeting role models and improving faculty performance but also by enhancing students’ reflective assessment of their preceptors’ behaviors, especially so that they can better discern those that are worth imitating. This student-centered approach may be accomplished by first, warning students against uncritically imitating preceptors who are perceived as role models; second, showing students that their preceptors share their doubts and uncertainties; third, gaining an insight into possible undesirable messages of the learning environment; and finally, developing policies for faculty recruitment and promotion that consider whether a clinical preceptor is a role model. PMID:24556777

  9. From the Arctic to fetal life: physiological importance and structural basis of an 'additional' chloride-binding site in haemoglobin.

    PubMed Central

    De Rosa, M Cristina; Castagnola, Massimo; Bertonati, Claudia; Galtieri, Antonio; Giardina, Bruno

    2004-01-01

    Haemoglobins from mammals of sub-Arctic and Arctic species, as well as fetal human Hb, are all characterized by a significantly lower Delta H of oxygenation compared with the majority of mammalian haemoglobins from temperate species (exceptions are represented by some cold-resistant species, such as cow, horse and pig). This has been interpreted as an adaptive mechanism of great importance from a physiological point of view. To date, the molecular basis of this thermodynamic characteristic is still not known. In the present study, we show that binding of extra chloride (with respect to adult human Hb) ions to Hb would significantly contribute to lowering the overall heat of oxygenation, thus providing a molecular basis for the low effect of temperature on the oxygenation-deoxygenation cycle. To this aim, the oxygen binding properties of bovine Hb, bear (Ursus arctos) Hb and horse Hb, which are representative of this series of haemoglobins, have been studied with special regard to the effect of heterotropic ligands, such as organic phosphates (namely 2,3-diphosphoglycerate) and chloride. Functional results are consistent with a mechanism for ligand binding that involves an additional binding site for chloride ion. Analysis of computational chemistry results, obtained by the GRID program, further confirm the hypothesis that the reason for the lower Delta H of oxygenation is mainly due to an increase in the number of the oxygen-linked chloride-binding sites. PMID:14979874

  10. a Study on the Role of Sintering Additives for Fabrication of sic Ceramic

    NASA Astrophysics Data System (ADS)

    Yoon, Han Ki; Lee, Young Ju; Cho, Ho Jun; Kim, Tae Gyu

    Silicon carbide (SiC) materials have been extensively studied for high temperature components in advanced energy system and advanced gas turbine. The SiC ceramics have been fabricated by a NITE (Nano Infiltration Transient Eutectic Phase) Process, using Nano-SiC powder. The sintering additives used for forming liquid phase under sintering process, used the sintering additives ratios were an Al2O3-Y2O3 system or add SiO2 contents. A major R&D focus for the SiC ceramics is the production to obtain high purity SiC ceramics. In this study, we investigated roles of the sintering additives(Al2O3:Y2O3) to fabrication of the SiC ceramics. The effects of SiO2 contents and density properties of the SiC ceramics were also investigated. To investigate the effects of SiO2, Al2O3/Y2O3 composition were fixed and then SiO2 ratios were changed as several kinds, and to confirm the effects of sintering additives ratios (Al2O3:Y2O3) they were changed between 4:6 and 6:4 in x wt.%.

  11. Longevity and relationships with children: the importance of the parental role

    PubMed Central

    Zunzunegui, Maria-Victoria; Béland, François; Sanchez, Maria-Teresa; Otero, Angel

    2009-01-01

    Background Social networks predict longevity across societies but specific mechanisms are largely unknown. The aim of this work was to examine the role of children in the longevity of elderly men and women in a cohort of community dwelling elderly people in Spain. Methods The data were taken from the "Aging in Leganes" cohort study with 15 years of follow-up. The baseline population was an age- and sex-stratified random sample of community dwelling people over 65 living in Leganés (Madrid) in 1993. Poor relationship with at least one child, emotional support and the perceived roles elders play in the lives of their children, extended family, spouse and friends were assessed at baseline. Cox proportional hazards models were fit to investigate the effects of social roles variables on longevity, adjusting for a wide range of socioeconomic, behavioural and health covariates. Results In the fully adjusted model, having a poor relationship with at least one child increased mortality by 30%. Elderly persons who felt their role in their children's lives was important (HR = 0.70; 95% CI 0.54; 0.91) had a lower mortality risk than those who felt they played a small role. Feeling loved and listened to by one's children did not have an effect on survival. Maintaining an important role in the extended family was also significantly associated with survival. Conclusion In this Mediterranean population, maintaining an important role in the lives of one's children is associated with survival. Functions of social networks related to meaning of life and different forms of social support may have important effects on mortality, and these functions may vary across cultures according to family norms and values. PMID:19765301

  12. The Role of Cocoa as a Cigarette Additive: Opportunities for Product Regulation

    PubMed Central

    Kennedy, Ryan David; Connolly, Gregory N.

    2014-01-01

    Introduction: The 2009 Family Smoking Prevention and Tobacco Control Act prohibited the use of characterizing flavors in cigarettes; however, some of these flavors are still used in cigarettes at varying levels. We reviewed tobacco industry internal documents to investigate the role of one of these flavors, cocoa, with the objective of understanding its relationship to sensory and risk perception, promotion of dependence, and enhancement of attractiveness and acceptability. Methods: We used the Legacy Tobacco Documents Library to identify documents relevant to our research questions. Initial search terms were generated following an examination of published literature on cocoa, other cigarette additives, and sensory and risk perception. Further research questions and search terms were generated based on review of documents generated from the initial search terms. Results: Cocoa is widely applied to cigarettes and has been used by the tobacco industry as an additive since the early 20th century. Cocoa can alter the sensory properties of cigarette smoke, including by providing a more appealing taste and decreasing its harshness. The tobacco industry has experimented with manipulating cocoa levels as a means of achieving sensory properties that appeal to women and youth. Conclusions: Although cocoa is identified as a flavor on tobacco industry Web sites, it may serve other sensory purposes in cigarettes as well. Eliminating cocoa as an additive from tobacco products may affect tobacco product abuse liability by altering smokers’ perceptions of product risk, and decreasing product appeal, especially among vulnerable populations. PMID:24610479

  13. The Importance of Positive Self-Concept for Islamic Education Teachers as a Role Model

    ERIC Educational Resources Information Center

    Muhamad, Nurul Asiah Fasehah; Hamzah, Mohd Isa; Tamuri, Ab. Halim; Ja'afar, Noornajihan; Ghazali, Norzulaili Mohd; Amat, Robiatul Adawiyah Mohd; Raus, Norakyairee Mohd; Hassan, Syed Najihuddin Syed

    2013-01-01

    This study embarks from the great and huge responsibility of teachers nowadays especially the IRT (Islamic religious teachers). As the role model of students, they play an important task especially in producing the good Muslim character. Therefore, their job not only focuses on the content of subject but becomes wider in scope, more than other…

  14. Redesigning and Transforming: A Case Study of the Role of Semiotic Import in Early Composing Processes

    ERIC Educational Resources Information Center

    Ranker, Jason

    2009-01-01

    In this article, I explore the role of semiotic import (Van Leeuwen, 2005) in the composing processes of three bilingual students (six to seven years old) emerging as writers of English. Using social semiotic (Van Leeuwen, 2005) and design (New London Group, 2000) frameworks, I trace a qualitative "micro-history" of how the students imported…

  15. Role of alloy additions on strengthening in 17-4 PH stainless steel

    NASA Astrophysics Data System (ADS)

    Murthy, Arpana Sudershan

    Alloy modifications by addition of niobium (Nb), vanadium (V), nitrogen (N) and cobalt (Co) to cast 17-4 PH steel were investigated to determine the effect on mechanical properties. Additions of Nb, V, and N increased the yield strength from 1120 MPa to 1310 MPa while decreased the room temperature charpy V notch (CVN) toughness from 20 J to four Joules. The addition of Co to cast 17-4 PH steel enhanced the yield strength and CVN toughness from 1140 MPa to 1290 MPa and from 3.7 J to 5.5 J, respectively. In the base 17-4 PH steel, an increase in block width from 2.27 ± 0.10 μm in the solution treated condition to 3.06 ± 0.17 μm upon aging at 755 K was measured using orientation image microscopy. Cobalt inhibited recrystallization and block boundary migration during aging resulting in a finer martensitic block structure. The influence of Co on copper (Cu) precipitation in steels was studied using atom probe tomography. A narrower precipitate size distribution was observed in the steels with Co addition. The concentration profile across the matrix / precipitate interface indicated rejection of Co atoms from the copper precipitates. This behavior was observed to be energetically favorable using first principle calculations. The activation energies for Cu precipitation increased from 205 kJ/ mol in the non-cobalt containing alloy, to 243 kJ/ mol, and 272 kJ/ mol in alloys with 3 wt. %Co, and 7 wt. % Co, respectively. The role of Co on Cu precipitation in cast 17-4 PH steel is proposed as follows: (i) Co is rejected out of the Cu precipitate and sets up a barrier to the growth of the Cu precipitate; (ii) results in Cu precipitates of smaller size and narrower distribution; (iii) the coarsening of Cu precipitates is inhibited; and (iv) the activation energy for Cu precipitation increases.

  16. Molecular Composition of Plant Vacuoles: Important but Less Understood Regulations and Roles of Tonoplast Lipids

    PubMed Central

    Zhang, Chunhua; Hicks, Glenn R.; Raikhel, Natasha V.

    2015-01-01

    The vacuole is an essential organelle for plant growth and development. It is the location for the storage of nutrients; such as sugars and proteins; and other metabolic products. Understanding the mechanisms of vacuolar trafficking and molecule transport across the vacuolar membrane is of great importance in understanding basic plant development and cell biology and for crop quality improvement. Proteins play important roles in vacuolar trafficking; such proteins include Rab GTPase signaling proteins; cargo recognition receptors; and SNAREs (Soluble NSF Attachment Protein Receptors) that are involved in membrane fusion. Some vacuole membrane proteins also serve as the transporters or channels for transport across the tonoplast. Less understood but critical are the roles of lipids in vacuolar trafficking. In this review, we will first summarize molecular composition of plant vacuoles and we will then discuss our latest understanding on the role of lipids in plant vacuolar trafficking and a surprising connection to ribosome function through the study of ribosomal mutants. PMID:27135331

  17. Molecular Composition of Plant Vacuoles: Important but Less Understood Regulations and Roles of Tonoplast Lipids.

    PubMed

    Zhang, Chunhua; Hicks, Glenn R; Raikhel, Natasha V

    2015-01-01

    The vacuole is an essential organelle for plant growth and development. It is the location for the storage of nutrients; such as sugars and proteins; and other metabolic products. Understanding the mechanisms of vacuolar trafficking and molecule transport across the vacuolar membrane is of great importance in understanding basic plant development and cell biology and for crop quality improvement. Proteins play important roles in vacuolar trafficking; such proteins include Rab GTPase signaling proteins; cargo recognition receptors; and SNAREs (Soluble NSF Attachment Protein Receptors) that are involved in membrane fusion. Some vacuole membrane proteins also serve as the transporters or channels for transport across the tonoplast. Less understood but critical are the roles of lipids in vacuolar trafficking. In this review, we will first summarize molecular composition of plant vacuoles and we will then discuss our latest understanding on the role of lipids in plant vacuolar trafficking and a surprising connection to ribosome function through the study of ribosomal mutants. PMID:27135331

  18. The mentor as a role model and the importance of belongingness.

    PubMed

    Vinales, James Jude

    Nursing staff are frontline workers and service users are constantly observing their behaviour and what, how and when they do things. Being professional at all times is essential for nurses and other health professionals. Student nurses in the learning environment will emulate staff nurses and mentors as role models for their future practice. This article will focus on the importance of role modelling and 'belongingness' in practice, and how mentors may influence the pre-registration student nurse while in the learning environment. This is the final article in a series of five articles on mentoring. PMID:26018020

  19. Role of Importance and Distinctiveness of Semantic Features in People with Aphasia: A Replication Study

    ERIC Educational Resources Information Center

    Mason-Baughman, Mary Beth; Wallace, Sarah E.

    2014-01-01

    Previous studies suggest that people with aphasia have incomplete lexical-semantic representations with decreased low-importance distinctive (LID) feature knowledge. In addition, decreased LID feature knowledge correlates with ability to discriminate among semantically related words. The current study seeks to replicate and extend previous…

  20. Is culture important in the choice of role models? Experiences from a culturally diverse medical school.

    PubMed

    McLean, Michelle

    2004-03-01

    In a multicultural student population at a South African medical school, for over one-third of students (Years 1-5) undertaking a traditional curriculum, culture was an important consideration in their choice of a role model. This was particularly so for senior students, perhaps reflecting their relatively recent exposure to patients and their forthcoming internship. Some student comments might, however, be interpreted as reflecting a rigid perception of culture that could translate into a possible lack of respect for other cultures. It is therefore imperative that each institution provide appropriate early and continuous mainstream diversity training, as well as identify role models to match the student profile. With the increasing diversity of students globally, this issue of culture should assume even greater importance in medical education than it is currently afforded. PMID:15203523

  1. A study on the role and importance of irrigation management in integrated river basin management.

    PubMed

    Koç, Cengiz

    2015-08-01

    The purpose of this paper is to identify the role and the importance of irrigation management in integrated river basin management during arid and semi-arid conditions. The study has been conducted at Büyük Menderes Basin which is located in southwest of Turkey and where different sectors (irrigation, drinking and using, industry, tourism, ecology) related to the use and distribution of water sources compete with each other and also where the water demands for important ecological considerations is evaluated and where the river pollution has reached important magnitudes. Since, approximately 73% of the water resources of the basin are utilized for irrigation; as a result, irrigation management becomes important for basin management. Irrigation operations have an effect on basin soil resources, water users, and environmental and ecological conditions. Thus, the determination of the role and importance of irrigation management require an integrated and interdisciplinary approach. In the studies conducted in Turkey, usually the environmental reactions have been analyzed in the basin studies and so the other topics related to integrated river basin management have not been taken into account. Therefore, this study also is to address these existing gaps in the literature and practice. PMID:26148688

  2. The Perceived Importance of Role-Specific Competencies for Health Care Leaders Establishes the Need to Expand Role Theory.

    PubMed

    Babinski, Paul J

    2016-01-01

    This cross-sectional quantitative study was undertaken to determine the extent to which individuals who have differing health care leadership roles perceived the importance of selected leadership competencies in their specific roles based on their experience. A total of 313 participants responded to the health care questionnaire. Principal component analysis identified factor structure and Cronbach α at .96 supported the reliability of the factor analysis. Multivariate analysis of variance tested the 4 health care leadership roles to determine if an effect was present among the competencies. A subsequent analysis of variance test was conducted on the competencies to confirm an effect was present, and a Games-Howell post hoc test followed. These tests indicated that there was a significant difference in rating the perceived importance of specific leadership competencies by the health care leaders in each competency domain. The participants included in this study consisted of the chief executive officer (CEO), director of nursing (DON), operating room director (ORD), and director of radiology (DOR). Based on the Games-Howell post hoc test, a commonality existed between the leaders. The CEOs and DONs often indicated no significant difference in competency perception to one another in relation to the dependent variables, yet indicated a significant difference in competency perception when compared with the ORDs and DORs. Similarly, the ORD and DOR variables often indicated no significant difference in competency perception to one another in relation to the dependent variables, yet indicated a significant difference in competency perception compared with the CEO and DON variables. This study positively indicated that health care leadership's perception of competencies does differ between the various leadership roles. PMID:27111689

  3. The Importance of the Partner: Supporting Nurse Leaders' Journey to Executive Roles.

    PubMed

    Blouin, Ann Scott

    2015-01-01

    Having a fully committed partner is an asset some nurse executives celebrate. The life partner can play a critical role in the nurse executive's career from a personal perspective. The importance of being flexible and balancing "who does what" and how to manage through life's challenges is reported through three nurse executives' stories and one spouse. Having a partner enriches the life journey, according to these leaders. PMID:26477122

  4. Presidential Roles: A Comparative Analysis of Their Relative Importance as Perceived by College and University Presidents and Governing Board Chairpersons.

    ERIC Educational Resources Information Center

    Cote, Lawrence S.

    The extent of agreement expressed by college presidents and governing board chairpersons concerning the relative importance of 20 selected presidential roles was assessed. The variables of institution size and type were also examined as they related to perceived presidential role importance. Based on role theory, attention was directed to whether…

  5. An Important Role of Pumilio 1 in Regulating the Development of the Mammalian Female Germline.

    PubMed

    Mak, Winifred; Fang, Caodi; Holden, Tobias; Dratver, Milana Bockhur; Lin, Haifan

    2016-06-01

    Pumilio/FBF (PUF) proteins are a highly conserved family of translational regulators. The Drosophila PUF protein, Pumilio, is crucial for germline establishment and fertility. In mammals, primordial folliculogenesis is a key process that establishes the initial cohort of female mammalian germ cells prior to birth, and this primordial follicle pool is a prerequisite for female reproductive competence. We sought to understand whether PUF proteins have a conserved role in mammals during primordial folliculogenesis and female reproductive competency. In mammals, two homologs of Pumilio exist: Pumilio 1 (Pum1) and Pum2. Here, we report that PUMILIO (PUM) 1 plays an important role in the establishment of the primordial follicle pool, meiosis, and female reproductive competency, whereas PUM2 does not have a detectable function in these processes. Furthermore, we show that PUM1 facilitates the transition of the late meiotic prophase I oocyte from pachytene to diplotene stage by regulating SYCP1 protein. Our study reveals an important role of translational regulation in mammalian female germ cell development. PMID:27170441

  6. Number line estimation and mental addition: examining the potential roles of language and education.

    PubMed

    Laski, Elida V; Yu, Qingyi

    2014-01-01

    This study investigated the relative importance of language and education to the development of numerical knowledge. Consistent with previous research suggesting that counting systems that transparently reflect the base-10 system facilitate an understanding of numerical concepts, Chinese and Chinese American kindergartners' and second graders' number line estimation (0-100 and 0-1000) was 1 to 2 years more advanced than that of American children tested in previous studies. However, Chinese children performed better than their Chinese American peers, who were fluent in Chinese but had been educated in America, at kindergarten on 0-100 number lines, at second grade on 0-1000 number lines, and at both time points on complex addition problems. Overall, the pattern of findings suggests that educational approach may have a greater influence on numerical development than the linguistic structure of the counting system. The findings also demonstrate that, despite generating accurate estimates of numerical magnitude on 0-100 number lines earlier, it still takes Chinese children approximately 2 years to demonstrate accurate estimates on 0-1000 number lines, which raises questions about how to promote the mapping of knowledge across numerical scales. PMID:24135313

  7. AtTMEM18 plays important roles in pollen tube and vegetative growth in Arabidopsis.

    PubMed

    Dou, Xiao-Ying; Yang, Ke-Zhen; Ma, Zhao-Xia; Chen, Li-Qun; Zhang, Xue-Qin; Bai, Jin-Rong; Ye, De

    2016-07-01

    In flowering plants, pollen tube growth is essential for delivery of male gametes into the female gametophyte or embryo sac for double fertilization. Although many genes have been identified as being involved in the process, the molecular mechanisms of pollen tube growth remains poorly understood. In this study, we identified that the Arabidopsis Transmembrane Protein 18 (AtTMEM18) gene played important roles in pollen tube growth. The AtTMEM18 shares a high similarity with the Transmembrane 18 proteins (TMEM18s) that are conserved in most eukaryotes and may play important roles in obesity in humans. Mutation in the AtTMEM18 by a Ds insertion caused abnormal callose deposition in the pollen grains and had a significant impact on pollen germination and pollen tube growth. AtTMEM18 is expressed in pollen grains, pollen tubes, root tips and other vegetative tissues. The pollen-rescued assays showed that the mutation in AtTMEM18 also caused defects in roots, stems, leaves and transmitting tracts. AtTMEM18-GFP was located around the nuclei. Genetic assays demonstrated that the localization of AtTMEM18 around the nuclei in the generative cells of pollen grains was essential for the male fertility. Furthermore, expression of the rice TMEM18-homologous protein (OsTMEM18) driven by LAT52 promoter could recover the fertility of the Arabidopsis attmem18 mutant. These results suggested that the TMEM18 is important for plant growth in Arabidopsis. PMID:26699939

  8. Thrombin Maybe Plays an Important Role in MK Differentiation into Platelets

    PubMed Central

    Yang, Xiao-Lei; Ge, Meng-Kai; Mao, De-Kui; Lv, Ying-Tao; Sun, Shu-Yan; Yu, Ai-Ping

    2016-01-01

    Objectives. After development and differentiation, megakaryocytes (MKs) can produce platelets. As is well known, thrombopoietin (TPO) can induce MKs to differentiate. The effect of thrombin on MKs differentiation is not clear. In this study, we used a human megakaryoblastic leukemia cell line (Meg-01) to assess the effect of thrombin on MKs differentiation. Methods. In order to interrogate the role of thrombin in Meg-01 cells differentiation, the changes of morphology, cellular function, and expression of diverse factors were analyzed. Results. The results show that thrombin suppresses Meg-01 cells proliferation and induces apoptosis and cell cycle arrest. Thrombin upregulates the expression of CD41b, which is one of the most important MK markers. Globin transcription factor 1 (GATA-1), an important transcriptional regulator, controls MK development and maturation. The expression of GATA-1 is also upregulated by thrombin in Meg-01 cells. The expression of B-cell lymphoma 2 (Bcl-2), an apoptosis-inhibitory protein, is downregulated by thrombin. Phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated by thrombin in Meg-01 cells. All the results are consistent with Meg-01 cells treated with TPO. Discussion and Conclusion. In conclusion, all these data indicate that thrombin maybe plays an important role in MK differentiation into platelets. However, whether the platelet-like particles are certainly platelets remains unknown. PMID:27064425

  9. Role of Anxiety in the Pathophysiology of Irritable Bowel Syndrome: Importance of the Amygdala

    PubMed Central

    Myers, Brent; Meerveld, Beverley Greenwood-Van

    2009-01-01

    A common characteristic of irritable bowel syndrome (IBS) is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI) tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala facilitating the activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor and glucocorticoid receptor-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS. PMID:20582274

  10. Important Role of the IL-32 Inflammatory Network in the Host Response against Viral Infection

    PubMed Central

    Zhou, Yaqin; Zhu, Ying

    2015-01-01

    The pro-inflammatory cytokine interleukin (IL)-32 has gained much attention recently because of its important role in the inflammatory network. Since the discovery of IL-32 in 2005, our appreciation for its diverse roles continues to grow. Recent studies have discovered the antiviral effects induced by IL-32 and its associated regulatory mechanisms. The interactions between IL-32 and various cytokines including cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), interferon (IFN)-λ1, interleukin (IL)-6, and soluble IL-6 receptor have been described. This review aims to integrate these new findings into explicit concepts and raises the intriguing possibility of IL-32 as a therapeutic target. PMID:26087456

  11. Phosphorus plays an important role in enhancing biodiesel productivity of Chlorella vulgaris under nitrogen deficiency.

    PubMed

    Chu, Fei-Fei; Chu, Pei-Na; Cai, Pei-Jie; Li, Wen-Wei; Lam, Paul K S; Zeng, Raymond J

    2013-04-01

    To investigate the role of phosphorus in lipid production under nitrogen starvation conditions, five types of media possessing different nitrogen and phosphorus concentrations or their combination were prepared to culture Chlorella vulgaris. It was found that biomass production under nitrogen deficient condition with sufficient phosphorus supply was similar to that of the control (with sufficient nutrition), resulting in a maximum lipid productivity of 58.39 mg/L/day. Meanwhile, 31P NMR showed that phosphorus in the medium was transformed and accumulated as polyphosphate in cells. The uptake rate of phosphorus in cells was 3.8 times higher than the uptake rate of the control. This study demonstrates that phosphorus plays an important role in lipid production of C. vulgaris under nitrogen deficient conditions and implies a potential to combine phosphorus removal from wastewater with biodiesel production via microalgae. PMID:23517904

  12. Important role of ventromedial hypothalamic carnitine palmitoyltransferase-1a in the control of food intake.

    PubMed

    Gao, Su; Serra, Dolors; Keung, Wendy; Hegardt, Fausto G; Lopaschuk, Gary D

    2013-08-01

    Carnitine palmitoyltransferase-1 (CPT-1) liver isoform, or CPT-1a, is implicated in CNS control of food intake. However, the exact brain nucleus site(s) in mediating this action of CPT-1a has not been identified. In this report, we assess the role of CPT-1a in hypothalamic ventromedial nucleus (VMN). We stereotaxically injected an adenoviral vector containing CPT-1a coding sequence into the VMN of rats to induce overexpression and activation of CPT-1a. The VMN-selective activation of CPT-1a induced an orexigenic effect, suggesting CPT-1a in the VMN is involved in the central control of feeding. Intracerebroventricular administration of etomoxir, a CPT-1 inhibitor, decreases food intake. Importantly, in the animals with VMN overexpression of a CPT-1a mutant that antagonizes the CPT-1 inhibition by etomoxir, the anorectic response to etomoxir was attenuated. This suggests that VMN is involved in mediating the anorectic effect of central inhibition of CPT-1a. In contrast, arcuate nucleus (Arc) overexpression of the mutant did not alter etomoxir-induced inhibition of food intake, suggesting that Arc CPT-1a does not play significant roles in this anorectic action. Furthermore, in the VMN, CPT-1a appears to act downstream of hypothalamic malonyl-CoA action of feeding. Finally, we show that in the VMN CPT-1 activity was altered in concert with fasting and refeeding states, supporting a physiological role of CPT-1a in mediating the control of feeding. All together, CPT-1a in the hypothalamic VMN appears to play an important role in central control of food intake. VMN-selective modulation of CPT-1a activity may therefore be a promising strategy in controlling food intake and maintaining normal body weight. PMID:23736540

  13. In Vivo Analysis of the Role of atTic20 in Protein Import into Chloroplasts

    PubMed Central

    Chen, Xuejun; Smith, Matthew D.; Fitzpatrick, Lynda; Schnell, Danny J.

    2002-01-01

    The import of nucleus-encoded preproteins into plastids requires the coordinated activities of membrane protein complexes that facilitate the translocation of polypeptides across the envelope double membrane. Tic20 was identified previously as a component of the import machinery of the inner envelope membrane by covalent cross-linking studies with trapped preprotein import intermediates. To investigate the role of Tic20 in preprotein import, we altered the expression of the Arabidopsis Tic20 ortholog (atTic20) by antisense expression. Several antisense lines exhibited pronounced chloroplast defects exemplified by pale leaves, reduced accumulation of plastid proteins, and significant growth defects. The severity of the phenotypes correlated directly with the reduction in levels of atTic20 expression. In vitro import studies with plastids isolated from control and antisense plants indicated that the antisense plastids are defective specifically in protein translocation across the inner envelope membrane. These data suggest that Tic20 functions as a component of the protein-conducting channel at the inner envelope membrane. PMID:11910011

  14. Neutral and charged clusters in the atmosphere - Their importance and potential role in heterogeneous catalysis

    NASA Technical Reports Server (NTRS)

    Castleman, A. W., Jr.

    1982-01-01

    An assessment is presented of current knowledge concerning the role and importance of neutral and charged clusters in atmospheric heterogeneous catalysis, with a view to the recommendation of future studies needed for progress in the quantification of aerosol formation and catalytic reactivity. It is established that nucleation from the gaseous to the aerosol state commences via the formation of clusters among molecules participating in the phase-transformation process. Nucleation may proceed in some cases by way of the formation of prenucleation embryos, which then evolve through the energy barrier and undergo phase transformation. In other cases, cluster-cluster interaction among neutral particles or stagewise building of alternate-sign ion clusters may be important in the gas-to-particle conversion process.

  15. Readiness for future managerial leadership roles: nursing students' perceived importance of organizational values.

    PubMed

    Hendel, Tova; Eshel, Nira; Traister, Lelit; Galon, Vered

    2006-01-01

    This study explored the values held by nursing students attending a baccalaureate program. Our aim was to determine whether nursing students' values change after being exposed to educators as well as mentors and ethics education and after experiencing today's challenging work environment, with an emphasis on the organizational domain of the students' values set. The conceptual framework that underpins the approach to values presented in this study argues that the total values set of a working person consists of three domains: personal, professional, and organizational values. Our sample consisted of first, third, and fourth year nursing students (N = 496) attending the Tel Aviv University in Israel. Participants were requested to answer a questionnaire and to rate their perceived importance of 30 values. The results revealed significant differences in the participants' perceived importance of the three values domains. The organizational values--the new business values--were perceived significantly to be least important. Sex was found to be significantly related to perception of values' importance. Year of study was not found to be significantly correlated to perception of values. The findings reflect that senior nursing students are only moderately prepared for their future managerial leadership roles and point out the need to provide students with more stimulating and supportive learning experiences. PMID:17141717

  16. hfq Plays Important Roles in Virulence and Stress Adaptation in Cronobacter sakazakii ATCC 29544

    PubMed Central

    Kim, Seongok; Hwang, Hyelyeon; Kim, Kwang-Pyo; Yoon, Hyunjin; Kang, Dong-Hyun

    2015-01-01

    Cronobacter spp. are opportunistic pathogens that cause neonatal meningitis and sepsis with high mortality in neonates. Despite the peril associated with Cronobacter infection, the mechanisms of pathogenesis are still being unraveled. Hfq, which is known as an RNA chaperone, participates in the interaction with bacterial small RNAs (sRNAs) to regulate posttranscriptionally the expression of various genes. Recent studies have demonstrated that Hfq contributes to the pathogenesis of numerous species of bacteria, and its roles are varied between bacterial species. Here, we tried to elucidate the role of Hfq in C. sakazakii virulence. In the absence of hfq, C. sakazakii was highly attenuated in dissemination in vivo, showed defects in invasion (3-fold) into animal cells and survival (103-fold) within host cells, and exhibited low resistance to hydrogen peroxide (102-fold). Remarkably, the loss of hfq led to hypermotility on soft agar, which is contrary to what has been observed in other pathogenic bacteria. The hyperflagellated bacteria were likely to be attributable to the increased transcription of genes associated with flagellar biosynthesis in a strain lacking hfq. Together, these data strongly suggest that hfq plays important roles in the virulence of C. sakazakii by participating in the regulation of multiple genes. PMID:25754196

  17. White matter hyperintensities and geriatric syndrome: An important role of arterial stiffness.

    PubMed

    Saji, Naoki; Ogama, Noriko; Toba, Kenji; Sakurai, Takashi

    2015-12-01

    White matter hyperintensities (WMH) are defined as cerebral white matter changes presumed to be of vascular origin, bilateral and mostly symmetrical. They can appear as hyperintense on T2-weighted and fluid-attenuated inversion recovery sequences, and as isointense or hypointense on T1-weighted magnetic resonance imaging of the brain. WMH have been focused on because of their clinical importance as a risk factor for cerebrovascular diseases and cognitive impairment. WMH are associated with geriatric syndrome, which is defined by clinical symptoms characteristic of older adults, including cognitive and functional impairment and falls. Cerebral small vessel diseases, such as WMH, might play an important role as risk factors for cerebrovascular diseases, cognitive impairment and geriatric syndrome through the mechanism of arterial stiffness. However, the vascular, physiological and metabolic roles of arterial stiffness remain unclear. Basically, arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. These changes might arise from hemodynamic stress as a result of a "tsunami effect" on cerebral parenchyma. In the present article, we review the clinical characteristics of WMH, focusing particularly on two associations: (i) those between cerebral small vessel diseases including WMH and arterial stiffness; and (ii) those between WMH and geriatric syndrome. PMID:26671153

  18. IQGAP1 Plays an Important Role in the Invasiveness of Thyroid Cancer

    PubMed Central

    Liu, Zhi; Liu, Dingxie; Bojdani, Ermal; El-Naggar, Adel K.; Vasko, Vasily; Xing, Mingzhao

    2010-01-01

    Purpose This study was designed to explore the role of IQGAP1 in the invasiveness of thyroid cancer and its potential as a novel prognostic marker and therapeutic target in this cancer. Experimental Design We examined IQGAP1 copy gain and its relationship with clinicopathological outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process. Results We found IQGAP1 copy number gain ≥ 3 in 1/30 (3%), 24/74 (32%), 44/107 (41%), 8/16 (50%), and 27/41 (66%) of benign thyroid tumor, follicular variant papillary thyroid cancer (FVPTC), follicular thyroid cancer (FTC), tall cell PTC, and anaplastic thyroid cancer, respectively, in the increasing order of invasiveness of these tumors. A similar tumor distribution trend of copy number ≥ 4 was also seen. IQGAP1 copy gain was positively correlated with IQGAP1 protein expression. It was significantly associated with extrathyroidal and vascular invasion of FVPTC and FTC and, remarkably, a 50–60% rate of multifocality and recurrence of BRAF mutation-positive PTC (P = 0.01 and 0.02, respectively). siRNA knockdown of IQGAP1 dramatically inhibited thyroid cancer cell invasion and colony formation. Co-immunoprecipitation assay demonstrated direct interaction of IQGAP1 with E-cadherin, a known invasion-suppressing molecule, which was up-regulated when IQGAP1 was knocked down. This provided a mechanism for the invasive role of IQGAP1 in thyroid cancer. In contrast, IQGAP3 lacked all these functions. Conclusions IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and may represent a novel prognostic marker and therapeutic target for this cancer. PMID:20959410

  19. Transcription Factor ets-2 Plays an Important Role in the Pathogenesis of Pulmonary Fibrosis

    PubMed Central

    Baran, Christopher P.; Fischer, Sara N.; Nuovo, Gerard J.; Kabbout, Mohamed N.; Hitchcock, Charles L.; Bringardner, Benjamin D.; McMaken, Sara; Newland, Christie A.; Cantemir-Stone, Carmen Z.; Phillips, Gary S.; Ostrowski, Michael C.

    2011-01-01

    Ets-2 is a ubiquitous transcription factor activated after phosphorylation at threonine-72. Previous studies highlighted the importance of phosphorylated ets-2 in lung inflammation and extracellular matrix remodeling, two pathways involved in pulmonary fibrosis. We hypothesized that phosphorylated ets-2 played an important role in pulmonary fibrosis, and we sought to determine the role of ets-2 in its pathogenesis. We challenged ets-2 (A72/A72) transgenic mice (harboring a mutated form of ets-2 at phosphorylation site threonine-72) and ets-2 (wild-type/wild-type [WT/WT]) control mice with sequential intraperitoneal injections of bleomycin, followed by quantitative measurements of lung fibrosis and inflammation and primary cell in vitro assays. Concentrations of phosphorylated ets-2 were detected via the single and dual immunohistochemical staining of murine lungs and lung sections from patients with idiopathic pulmonary fibrosis. Ets-2 (A72/A72) mice were protected from bleomycin-induced pulmonary fibrosis, compared with ets-2 (WT/WT) mice. This protection was characterized by decreased lung pathological abnormalities and the fibrotic gene expression of Type I collagen, Type III collagen, α–smooth muscle actin, and connective tissue growth factor. Immunohistochemical staining of lung sections from bleomycin-treated ets-2 (WT/WT) mice and from patients with idiopathic pulmonary fibrosis demonstrated increased staining of phosphorylated ets-2 that colocalized with Type I collagen expression and to fibroblastic foci. Lastly, primary lung fibroblasts from ets-2 (A72/A72) mice exhibited decreased expression of Type I collagen in response to stimulation with TGF-β, compared with fibroblasts from ets-2 (WT/WT) mice. These data indicate the importance of phosphorylated ets-2 in the pathogenesis of pulmonary fibrosis through the expression of Type I collagen and (myo)fibroblast activation. PMID:21562315

  20. Transcription factor ets-2 plays an important role in the pathogenesis of pulmonary fibrosis.

    PubMed

    Baran, Christopher P; Fischer, Sara N; Nuovo, Gerard J; Kabbout, Mohamed N; Hitchcock, Charles L; Bringardner, Benjamin D; McMaken, Sara; Newland, Christie A; Cantemir-Stone, Carmen Z; Phillips, Gary S; Ostrowski, Michael C; Marsh, Clay B

    2011-11-01

    Ets-2 is a ubiquitous transcription factor activated after phosphorylation at threonine-72. Previous studies highlighted the importance of phosphorylated ets-2 in lung inflammation and extracellular matrix remodeling, two pathways involved in pulmonary fibrosis. We hypothesized that phosphorylated ets-2 played an important role in pulmonary fibrosis, and we sought to determine the role of ets-2 in its pathogenesis. We challenged ets-2 (A72/A72) transgenic mice (harboring a mutated form of ets-2 at phosphorylation site threonine-72) and ets-2 (wild-type/wild-type [WT/WT]) control mice with sequential intraperitoneal injections of bleomycin, followed by quantitative measurements of lung fibrosis and inflammation and primary cell in vitro assays. Concentrations of phosphorylated ets-2 were detected via the single and dual immunohistochemical staining of murine lungs and lung sections from patients with idiopathic pulmonary fibrosis. Ets-2 (A72/A72) mice were protected from bleomycin-induced pulmonary fibrosis, compared with ets-2 (WT/WT) mice. This protection was characterized by decreased lung pathological abnormalities and the fibrotic gene expression of Type I collagen, Type III collagen, α-smooth muscle actin, and connective tissue growth factor. Immunohistochemical staining of lung sections from bleomycin-treated ets-2 (WT/WT) mice and from patients with idiopathic pulmonary fibrosis demonstrated increased staining of phosphorylated ets-2 that colocalized with Type I collagen expression and to fibroblastic foci. Lastly, primary lung fibroblasts from ets-2 (A72/A72) mice exhibited decreased expression of Type I collagen in response to stimulation with TGF-β, compared with fibroblasts from ets-2 (WT/WT) mice. These data indicate the importance of phosphorylated ets-2 in the pathogenesis of pulmonary fibrosis through the expression of Type I collagen and (myo)fibroblast activation. PMID:21562315

  1. The role of human carboxylesterases in drug metabolism: have we overlooked their importance?

    PubMed Central

    Laizure, S. Casey; Herring, Vanessa; Hu, Zheyi; Witbrodt, Kevin; Parker, Robert B.

    2012-01-01

    Carboxylesterases are a multi-gene family of enzymes widely distributed throughout the body of mammals that catalyze the hydrolysis of esters, amides, thioesters, and carbamates. In humans, two carboxylesterases, hCE1 and hCE2, are important pathways of drug metabolism. Both are expressed in the liver, but levels of hCE1 greatly exceed those of hCE2. In the intestine only high levels of hCE2 are expressed. The most common drug substrates are ester prodrugs specifically designed to enhance oral bioavailability that must be hydrolyzed to their active carboxylic acid by hydrolysis after absorption from the gastrointestinal tract. However, carboxylesterases also play an important role in the hydrolysis of some drugs to inactive metabolites. It has been widely accepted that drugs undergoing hydrolysis by hCE1 and hCE2 are not subject to clinically significant alterations in their disposition, but there is now a significant and growing body of evidence that genetic polymorphisms, drug-drug interactions, drug-disease interactions and other factors are important determinants of the variability in the therapeutic response to carboxylesterase-substrate drugs. The implications for the safe and effective use of drug therapy is far-reaching, as the patient exposure to substrate drugs includes numerous agents from widely prescribed therapeutic classes such as angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, antiplatelets, HMG-CoA inhibitors, antivirals, and central nervous system agents. PMID:23386599

  2. Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia in mice.

    PubMed

    Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

    2015-12-01

    Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the last decade, affecting about 2 to 5% pregnant women. Even among women who have gestational hyperglycemia may also be positively related to adverse outcomes as GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with diabetes and insulin resistance and its expression was reported to be negatively regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a role in a gestational hyperglycemia mouse model. Mice were divided into non-pregnant and pregnant groups, and each comprised three subgroups: control, high-fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of triglycerides, total cholesterol, glucose, and insulin, as well as conducted thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides, total cholesterol, glucose, and insulin levels in the serum. Additionally, thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship correlation between Hsp70 and BAT functions. Hsp70 level is associated with hyperglycemia during pregnancy. Our results support the role of Hsp70 in facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3 pathway. PMID:26318018

  3. Role of inorganic additives on the ballistic performance of gun propellant formulations.

    PubMed

    Damse, R S; Sikder, A K

    2008-06-15

    This paper explores the possibility of increasing the ballistic performance of gun propellant with the addition of inorganic additives viz. aluminium and ammonium perchlorate. Compositions based on propellant NQ containing additional aluminium and ammonium perchlorate in different parts were studied theoretically and experimentally. Performance in respect of ballistic parameters, sensitivity, thermal characteristics, thermal stability and mechanical properties are evaluated and compared with that of the conventional triple base propellant NQ. Experimental data on comparative study indicate that the compositions containing aluminium and ammonium perchlorate are superior to propellant NQ in respect of energy. PMID:18206299

  4. Platelet to lymphocyte ratio plays an important role in prostate cancer’s diagnosis and prognosis

    PubMed Central

    Li, Feng; Hu, Haibo; Gu, Shuo; Chen, Xin; Sun, Qing

    2015-01-01

    Objective: To compare the platelet to lymphocyte ratio (PLR) in normal people, benign prostatic hyperplasia (BPH) patients and prostate cancer (PCA) patients, and to explore the prognostic role of PLR in PCA. Methods: 155 normal people, 168 BPH patients and 103 PCA patients were enrolled. PCA patients were divided into PLR low value group (PLR<150) and PLR high value group (PLR≥150), and the difference of patients’ clinical characteristics between high value group and low value group was comparative studied.Results: The differences of PLR among normal people, BPH patients and PCA patients were statistically significant. In addition, platelet counts, neutrophil counts, PSA level, LDH level, AKP level, CRP level and alkaline phosphatase level were also significantly increased in PLR high value group, while the hemoglobin level was decreased. Besides, serious events such as coma during hospitalization were also more likely to appear in PLR high value group. PCA patients had an average follow-up of 3 years, and a total of 25 cases of patients died, including 11 (16.4%) cases in the PLR low value group, and 14 (38.9%) cases in PLR high value group with. Three years survival rate of patients in high value group was significantly reduced. Additionally, PLR was a possible risk factor associated with mortality, and an independent predictor of all-cause mortality during follow-up. Conclusion: PLR is significantly increased in PCA patients, and it is an independent predictor of 3-year mortality in PCA patients. PMID:26380014

  5. The role and importance of club cells (Clara cells) in the pathogenesis of some respiratory diseases

    PubMed Central

    Rokicki, Marek; Wojtacha, Jacek; Dżeljijli, Agata

    2016-01-01

    The report presents the cellular structure of the respiratory system as well as the history of club cells (Clara cells), their ultrastructure, and location in the airways and human organs. The authors discuss the biochemical structure of proteins secreted by these cells and their importance for the integrity and regeneration of the airway epithelium. Their role as progenitor cells for the airway epithelium and their involvement in the biotransformation of toxic xenobiotics introduced into the lungs during breathing is emphasized. This is followed by a discussion of the clinical aspects associated with club cells, demonstrating that tracking the serum concentration of club cell-secreted proteins is helpful in the diagnosis of a number of lung tissue diseases. Finally, suggestions are provided regarding the possible use of proteins secreted by club cells in the treatment of serious respiratory conditions. PMID:27212975

  6. Conserved type III secretion system exerts important roles in Chlamydia trachomatis

    PubMed Central

    Dai, Wenting; Li, Zhongyu

    2014-01-01

    Upon infection, Chlamydiae alter host cellular functions in a variety of ways. Chlamydial infection prevents host cell apoptosis, induces re-organization of the actin cytoskeleton and alters host cellular signaling mechanisms. Chlamydia is among the many pathogenic Gram-negative bacteria that employ the type III secretion system (T3SS) to overcome host defenses and exploit available resources. T3SS are used by many Gram-negative bacterial pathogens to manipulate eukaryotic host cells through the delivery of effector proteins into their cytosol and membranes. T3SS is an evolutionarily refined, virulence determinant of Gram-negative bacteria where more than 20 proteins form an apparatus, generally termed injectisome, to achieve the vectorial secretion and translocation of anti-host effector proteins. This review describes challenges and recent advances that have revealed how Chlamydia trachomatis utilizes diversification to produce a conserved T3SS that exerts an important role in Chlamydia trachomatis. PMID:25337183

  7. The role and importance of club cells (Clara cells) in the pathogenesis of some respiratory diseases.

    PubMed

    Rokicki, Wojciech; Rokicki, Marek; Wojtacha, Jacek; Dżeljijli, Agata

    2016-03-01

    The report presents the cellular structure of the respiratory system as well as the history of club cells (Clara cells), their ultrastructure, and location in the airways and human organs. The authors discuss the biochemical structure of proteins secreted by these cells and their importance for the integrity and regeneration of the airway epithelium. Their role as progenitor cells for the airway epithelium and their involvement in the biotransformation of toxic xenobiotics introduced into the lungs during breathing is emphasized. This is followed by a discussion of the clinical aspects associated with club cells, demonstrating that tracking the serum concentration of club cell-secreted proteins is helpful in the diagnosis of a number of lung tissue diseases. Finally, suggestions are provided regarding the possible use of proteins secreted by club cells in the treatment of serious respiratory conditions. PMID:27212975

  8. Importance And Role Of Competence In Professional Career Of Product Develop Engineers

    NASA Astrophysics Data System (ADS)

    Miltenović, Aleksandar; Banić, Milan; Miltenović, Vojislav

    2015-07-01

    Product development is a creative task where is systematically created a new product, which makes possible to firms to offer attractive, innovative and market oriented products. In conditions of fierce competition and saturated markets, companies that do not innovate are stagnating and disappear from the market. Innovation is therefore every intervention which can reduce production costs, enables optimum utilization of available human, energy and material resources, improve product quality, improve the placement, which leads to an increase in competitiveness. A prerequisite for fulfillment of the above-mentioned tasks is that the companies have engineers with the appropriate competencies, which are able to, through creativity, innovation and fascinating technique of creating new or improving existing products and lunch it on the market. The paper discusses the role and importance of the competences that are necessary for a successful professional career of product development engineers.

  9. TGF-β signaling plays an important role in resisting γ-irradiation

    SciTech Connect

    An, You Sun; Kim, Mi-Ra; Lee, Seung-Sook; Lee, Yun-Sil; Chung, Eunkyung; Song, Jie-Young; Lee, Jeeyong; Yi, Jae Youn

    2013-02-15

    Transforming growth factor-β1 (TGF-β1) regulates various biological processes, including differentiation, bone remodeling and angiogenesis, and is particularly important as a regulator of homeostasis and cell growth in normal tissue. Interestingly, some studies have reported that TGF-β1 induces apoptosis through induction of specific genes, whereas others suggest that TGF-β1 inhibits apoptosis and facilitates cell survival. Resolving these discrepancies, which may reflect differences in cellular context, is an important research priority. Here, using the parental mink lung epithelial cell line, Mv1Lu, and its derivatives, R1B and DR26, lacking TGF-β receptors, we investigated the involvement of TGF-β signaling in the effects of γ-irradiation. We found that canonical TGF-β signaling played an important role in protecting cells from γ-irradiation. Introduction of functional TGF-β receptors or constitutively active Smads into R1B and DR26 cell lines reduced DNA fragmentation, Caspase-3 cleavage and γ-H2AX foci formation in γ-irradiated cells. Notably, we also found that de novo protein synthesis was required for the radio-resistant effects of TGF-β1. Our data thus indicate that TGF-β1 protected against γ-irradiation, decreasing DNA damage and reducing apoptosis, and thereby enhanced cell survival. - Highlights: ► TGF-β1 pretreatment inhibits γ-irradiation-induced apoptosis. ► TGF-β signaling reduces γ-irradiation-induced γ-H2AX foci formation. ► de novo protein synthesis is necessary for TGF-β1-induced radio-resistance.

  10. The Role of Additional Processing Time and Lexical Constraint in Spoken Word Recognition

    ERIC Educational Resources Information Center

    LoCasto, Paul C.; Connine, Cynthia M.; Patterson, David

    2007-01-01

    Three phoneme monitoring experiments examined the manner in which additional processing time influences spoken word recognition. Experiment 1a introduced a version of the phoneme monitoring paradigm in which a silent interval is inserted prior to the word-final target phoneme. Phoneme monitoring reaction time decreased as the silent interval…

  11. Latinas and Postpartum Depression: Role of Partner Relationship, Additional Children, and Breastfeeding

    ERIC Educational Resources Information Center

    Hassert, Silva; Kurpius, Sharon E. Robinson

    2011-01-01

    Breastfeeding, additional children, and partner relationship predicted postpartum depression among 59 Latinas who had an infant who was 6 months old or younger. The most powerful predictor was conflict with partner. Counselors working with Latinas experiencing postpartum depression should explore the partner relationship, particularly relationship…

  12. Testing a Gender Additive Model: The Role of Body Image in Adolescent Depression

    ERIC Educational Resources Information Center

    Bearman, Sarah Kate; Stice, Eric

    2008-01-01

    Despite consistent evidence that adolescent girls are at greater risk of developing depression than adolescent boys, risk factor models that account for this difference have been elusive. The objective of this research was to examine risk factors proposed by the "gender additive" model of depression that attempts to partially explain the increased…

  13. Galectin-3 Plays an Important Role in Innate Immunity to Gastric Infection by Helicobacter pylori.

    PubMed

    Park, Ah-Mee; Hagiwara, Satoru; Hsu, Daniel K; Liu, Fu-Tong; Yoshie, Osamu

    2016-04-01

    We studied the role of galectin-3 (Gal3) in gastric infection by Helicobacter pylori We first demonstrated that Gal3 was selectively expressed by gastric surface epithelial cells and abundantly secreted into the surface mucus layer. We next inoculated H. pylori Sydney strain 1 into wild-type (WT) and Gal3-deficient mice using a stomach tube. At 2 weeks postinoculation, the bacterial cells were mostly trapped within the surface mucus layer in WT mice. In sharp contrast, they infiltrated deep into the gastric glands in Gal3-deficient mice. Bacterial loads in the gastric tissues were also much higher in Gal3-deficient mice than in WT mice. At 6 months postinoculation,H. pylori had successfully colonized within the gastric glands of both WT and Gal3-deficient mice, although the bacterial loads were still higher in the latter. Furthermore, large lymphoid clusters mostly consisting of B cells were frequently observed in the gastric submucosa of Gal3-deficient mice.In vitro, peritoneal macrophages from Gal3-deficient mice were inefficient in killing engulfed H. pylori Furthermore, recombinant Gal3 not only induced rapid aggregation of H. pylori but also exerted a potent bactericidal effect on H. pylori as revealed by propidium iodide uptake and a morphological shift from spiral to coccoid form. However, a minor fraction of bacterial cells, probably transient phase variants of Gal3-binding sugar moieties, escaped killing by Gal3. Collectively, our data demonstrate that Gal3 plays an important role in innate immunity to infection and colonization of H. pylori. PMID:26857579

  14. Structure and Function of Human Xylulokinase, an Enzyme with Important Roles in Carbohydrate Metabolism*

    PubMed Central

    Bunker, Richard D.; Bulloch, Esther M. M.; Dickson, James M. J.; Loomes, Kerry M.; Baker, Edward N.

    2013-01-01

    d-Xylulokinase (XK; EC 2.7.1.17) catalyzes the ATP-dependent phosphorylation of d-xylulose (Xu) to produce xylulose 5-phosphate (Xu5P). In mammals, XK is the last enzyme in the glucuronate-xylulose pathway, active in the liver and kidneys, and is linked through its product Xu5P to the pentose-phosphate pathway. XK may play an important role in metabolic disease, given that Xu5P is a key regulator of glucose metabolism and lipogenesis. We have expressed the product of a putative human XK gene and identified it as the authentic human d-xylulokinase (hXK). NMR studies with a variety of sugars showed that hXK acts only on d-xylulose, and a coupled photometric assay established its key kinetic parameters as Km(Xu) = 24 ± 3 μm and kcat = 35 ± 5 s−1. Crystal structures were determined for hXK, on its own and in complexes with Xu, ADP, and a fluorinated inhibitor. These reveal that hXK has a two-domain fold characteristic of the sugar kinase/hsp70/actin superfamily, with glycerol kinase as its closest relative. Xu binds to domain-I and ADP to domain-II, but in this open form of hXK they are 10 Å apart, implying that a large scale conformational change is required for catalysis. Xu binds in its linear keto-form, sandwiched between a Trp side chain and polar side chains that provide exquisite hydrogen bonding recognition. The hXK structure provides a basis for the design of specific inhibitors with which to probe its roles in sugar metabolism and metabolic disease. PMID:23179721

  15. D-Aspartic acid: an endogenous amino acid with an important neuroendocrine role.

    PubMed

    D'Aniello, Antimo

    2007-02-01

    D-Aspartic acid (d-Asp), an endogenous amino acid present in vertebrates and invertebrates, plays an important role in the neuroendocrine system, as well as in the development of the nervous system. During the embryonic stage of birds and the early postnatal life of mammals, a transient high concentration of d-Asp takes place in the brain and in the retina. d-Asp also acts as a neurotransmitter/neuromodulator. Indeed, this amino acid has been detected in synaptosomes and in synaptic vesicles, where it is released after chemical (K(+) ion, ionomycin) or electric stimuli. Furthermore, d-Asp increases cAMP in neuronal cells and is transported from the synaptic clefts to presynaptic nerve cells through a specific transporter. In the endocrine system, instead, d-Asp is involved in the regulation of hormone synthesis and release. For example, in the rat hypothalamus, it enhances gonadotropin-releasing hormone (GnRH) release and induces oxytocin and vasopressin mRNA synthesis. In the pituitary gland, it stimulates the secretion of the following hormones: prolactin (PRL), luteinizing hormone (LH), and growth hormone (GH) In the testes, it is present in Leydig cells and is involved in testosterone and progesterone release. Thus, a hypothalamus-pituitary-gonads pathway, in which d-Asp is involved, has been formulated. In conclusion, the present work is a summary of previous and current research done on the role of d-Asp in the nervous and endocrine systems of invertebrates and vertebrates, including mammals. PMID:17118457

  16. Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

    NASA Technical Reports Server (NTRS)

    Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

    2003-01-01

    Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4

  17. A role of BNLT compound addition on structure and properties of PZT ceramics

    NASA Astrophysics Data System (ADS)

    Jaita, P.; Watcharapasorn, A.; Jiansirisomboon, S.

    2010-09-01

    In this research, effects of lead-free bismuth sodium lanthanum titanate (BNLT) addition on structure and properties of lead zirconate titanate (PZT) ceramics were investigated. PZT ceramics with addition of 0.1-3.0 wt%BNLT were fabricated by a solid-state mixed oxide method and sintering at 1050-1200 °C for 2 h to obtain dense ceramics with at least 96% of theoretical density. X-ray diffraction indicated that complete solid solution occurred for all compositions. Phase identification showed both tetragonal and rhombohedral perovskite structure of PZT with no BNLT phase detected. Scanning electron micrographs of fractured PZT/BNLT ceramics showed equiaxed grain shape with both transgranular and intergranular fracture modes. Addition of BNLT was also found to reduce densification and effectively limited grain growth of PZT ceramic. Optimum Hv and KIC values were found to be 4.85 GPa and 1.56 MPa.m 1/2 for PZT/0.5 wt%BNLT sample. Among PZT/BNLT samples, room temperature dielectric constant seemed to be improved with increasing BNLT content. The maximum piezoelectric coefficient values were observed in pure PZT ceramic and were slightly decreased in BNLT-added samples. Small reduction of remanent polarization and coercive field in hysteresis loops was observed in BNLT-added samples, indicating a slightly suppressed ferroelectric interaction in this material system.

  18. Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells.

    PubMed

    Wang, Ronghua; Sun, Qian; Wang, Peng; Liu, Man; Xiong, Si; Luo, Jing; Huang, Hai; Du, Qiang; Geller, David A; Cheng, Bin

    2016-02-01

    Human hepatocellular carcinoma (HCC) is driven and maintained by liver cancer stem cells (LCSCs) that display stem cell properties. These LCSCs are promoted by the intersecting of Notch and Wnt/β-Catenin signaling pathways. In this study, we demonstrate that LCSCs with markers CD90, CD24, CD13, and CD133 possess stem properties of self-renewal and tumorigenicity in NOD/SCID mice. The increased expression of these markers was correlated with advanced disease stage, larger tumors, and worse overall survival in 61 HCC cases. We also found that both Notch and Wnt/β-catenin signaling pathways played important roles in increasing the stem-ness characteristics of LCSCs. Our data suggested that Notch1 was downstream of Wnt/β-catenin. The active form of Notch1 intracellular domain (NICD) expression depended on Wnt/β-catenin pathway activation. Moreover, Notch1 negatively contributed to Wnt/β-catenin signaling modulation. Knock down of Notch1 with lentivirus N1ShRNA up-regulated the active form of β-catenin. Ectopic expression of NICD with LV-Notch1 in LCSCs attenuated β-catenin/TCF dependent luciferase activity significantly. In addition, there was a non-proteasome mediated feedback loop between Notch1 and Wnt/β-catenin signaling in LCSCs. The central role of Notch and the Wnt/β-catenin signaling pathway in LCSCs may provide an attractive therapeutic strategy against HCC. PMID:26735577

  19. Genome-wide meta-analysis of maize heterosis reveals the potential role of additive gene expression at pericentromeric loci

    PubMed Central

    2014-01-01

    QTL, and also suggests a model for the potential role of additive expression in the formation and conservation of heterosis for GY via dominant, multigenic quantitative trait loci. Our findings contribute to a deeper understanding of the multifactorial phenomenon of heterosis, and thus to the breeding of new high yielding varieties. PMID:24693880

  20. Additional role of second washing specimen obtained during single bronchoscopy session in diagnosis of pulmonary tuberculosis

    PubMed Central

    2013-01-01

    Background Flexible bronchoscopy with bronchial washing is a useful procedure for diagnosis of pulmonary tuberculosis (TB), when a patient cannot produce sputum spontaneously or when sputum smears are negative. However, the benefit of gaining serial bronchial washing specimens for diagnosis of TB has not yet been studied. Therefore, we conducted a retrospective study to determine the diagnostic utility of additional bronchial washing specimens for the diagnosis of pulmonary TB in suspected patients. Methods A retrospective analysis was performed on 174 patients [sputum smear-negative, n = 95 (55%); lack of sputum specimen, n = 79 (45%)] who received flexible bronchoscopy with two bronchial washing specimens with microbiological confirmation of pulmonary TB in Samsung Medical Center, between January, 2010 and December, 2011. Results Pulmonary TB was diagnosed by first bronchial washing specimen in 141 patients (81%) out of 174 enrolled patients, and an additional bronchial washing specimen established diagnosis exclusively in 22 (13%) patients. Smear for acid-fast bacilli (AFB) was positive in 46 patients (26%) for the first bronchial washing specimen. Thirteen patients (7%) were positive only on smear of an additional bronchial washing specimen. Combined smear positivity of the first and second bronchial washing specimens was significantly higher compared to first bronchial washing specimen alone [Total cases: 59 (34%) vs. 46 (26%), p < 0.001; cases for smear negative sputum: 25 (26%) vs. 18 (19%), p = 0.016; cases for poor expectoration: 34 (43%) vs. 28 (35%), p = 0.031]. The diagnostic yield determined by culture was also significantly higher in combination of the first and second bronchial washing specimens compared to the first bronchial washing. [Total cases: 163 (94%) vs. 141 (81%), p < 0.001; cases for smear negative sputum: 86 (91%) vs. 73 (77%), p < 0.001; cases for poor expectoration: 77 (98%) vs. 68 (86%), p = 0

  1. The Important Role of T Cells and Receptor Expression in Sjögren's Syndrome

    PubMed Central

    Karabiyik, A.; Peck, A. B.; Nguyen, C. Q.

    2015-01-01

    Sjögren's syndrome (SjS), an autoimmune disease characterized by exocrine gland dysfunction leading to dry mouth and dry eye diseases, is typified by progressive leucocyte infiltrations of the salivary and lacrimal glands. Histologically, these leucocyte infiltrations generally establish periductal aggregates, referred to as lymphocytic foci (LF), which occasionally appear as germinal centre (GC)-like structures. The formation and organization of these LF suggest an important and dynamic role for helper T cells (TH), specifically TH1, TH2 and the recently discovered TH17, in development and onset of clinical SjS, considered a B cell–mediated hypersensitivity type 2 disease. Despite an ever-increasing focus on identifying the underlying aetiology of SjS, defining factors that initiate this autoimmune disease remain a mystery. Thus, determining interactions between infiltrating TH cells and exocrine gland tissue (auto-)antigens represents a fertile research endeavour. This review discusses pathological functions of TH cells in SjS, the current status of TH cell receptor gene rearrangements associated with human and mouse models of SjS and potential future prospects for identifying receptor–autoantigen interactions. PMID:23679844

  2. Arabidopsis abscisic acid receptors play an important role in disease resistance.

    PubMed

    Lim, Chae Woo; Lee, Sung Chul

    2015-06-01

    Stomata are natural pores of plants and constitute the entry points for water during transpiration. However, they also facilitate the ingress of potentially harmful bacterial pathogens. The phytohormone abscisic acid (ABA) plays a pivotal role in protecting plants against biotic stress, by regulating stomatal closure. In the present study, we investigated the mechanism whereby ABA influences plant defense responses to Pseudomonas syringae pv. tomato (Pst) DC3000, which is a virulent bacterial pathogen of Arabidopsis, at the pre-invasive stage. We found that overexpression of two ABA receptors, namely, RCAR4/PYL10-OX and RCAR5/PYL11-OX (hereafter referred to as RCARs), resulted in ABA-hypersensitive phenotypes being exhibited during the seed germination and seedling growth stages. Sensitivity to ABA enhanced the resistance of RCAR4-OX and RCAR5-OX plants to Pst DC3000, through promoting stomatal closure leading to the development of resistance to this bacterial pathogen. Protein phosphatase HAB1 is an important component that is responsible for ABA signaling and which interacts with ABA receptors. We found that hab1 mutants exhibited enhanced resistance to Pst DC3000; moreover, similar to RCAR4-OX and RCAR5-OX plants, this enhanced resistance was correlated with stomatal closure. Taken together, our findings demonstrate that alteration of RCAR4- or RCAR5-HAB1 mediated ABA signaling influences resistance to bacterial pathogens via stomatal regulation. PMID:25969135

  3. Heterocystous Cyanobacteria in Microbialites Play an Important Role in N2 Fixation and Carbonate Mineral Precipitation

    NASA Astrophysics Data System (ADS)

    Alcantara-Hernandez, R. J.

    2015-12-01

    Lake Alchichica is a maars type crater-lake located in Central Mexico (pH > 8.9, EC ~13.39 mS cm-1). This limnological system harbors two types of microbialites that can be found around the entire perimeter of the lake (Fig. 1). These structures are representative examples of complex and diverse microbiological assemblages, where microbial activity promotes lithification by trapping, binding and/or precipitating detrital or chemical sediments. Previous studies determined that the microbialites of Lake Alchichica fix N2 to thrive under the N-limiting conditions of the lake, and that these nitrogenase activity peaks are related to heterocystous cyanobacteria that couple photosynthesis to N2 fixation during daylight periods. Heterocystous cyanobacteria (Nostocales) together with Oscillatoriales (non-heterocystous filamentous cyanobacteria) and other cyanobacterial groups have been described as the most abundant cyanobacteria in Alchichica microbialites, and in lithifying mats. Our results suggest that heterocystous cyanobacteria play an important role not only by fixing N2 for biomass construction, but also because their heterocysts host in their external cell membranes main sites for carbonate mineral precipitation including calcium carbonates and siderite. Previous research has shown that the heterocyst is the specialized site for cellular respiration associated to the pH decrease of vegetative/photosynthetic cells, contributing thus to the precipitation of carbonates and the accretion of the organosedimentary structure

  4. Central dopaminergic neurotransmission plays an important role in thermoregulation and performance during endurance exercise.

    PubMed

    Zheng, Xinyan; Hasegawa, Hiroshi

    2016-10-01

    Dopamine (DA) has been widely investigated for its potential role in determining exercise performance. It was originally thought that DA's ergogenic effect was by mediating psychological responses. Recently, some studies have also suggested that DA may regulate physiological responses, such as thermoregulation. Hyperthermia has been demonstrated as an important limiting factor during endurance exercise. DA is prominent in the thermoregulatory centre, and changes in DA concentration have been shown to affect core temperature regulation during exercise. Some studies have proposed that DA or DA/noradrenaline (NA) reuptake inhibitors can improve exercise performance, despite hyperthermia during exercise in the heat. DA/NA reuptake inhibitors also increase catecholamine release in the thermoregulatory centre. Intracerebroventricularly injected DA has been shown to improve exercise performance through inhibiting hyperthermia-induced fatigue, even at normal ambient temperatures. Further, caffeine has been reported to increase DA release in the thermoregulatory centre and improves endurance exercise performance despite increased core body temperature. Taken together, DA has been shown to have ergogenic effects and increase heat storage and hyperthermia tolerance. The mechanisms underlying these effects seem to involve limiting/overriding the inhibitory signals from the central nervous system that result in cessation of exercise due to hyperthermia. PMID:26581447

  5. [Roles of additives and surface control in slurry atomization]. Quarterly report

    SciTech Connect

    Tsai, S.C.

    1992-06-01

    As reported in the quarterly report of March of 1992, the relative viscosity of a Newtonian Coal Water Slurry (CWS) in the presence of an anionic polymeric dispersant is an order of magnitude higher than the prediction of the well established Krieger-Dougherty Equation which describes the relative viscosity of a non-aggregated Newtonian suspension as a function of particle volume fraction. Note that the anionic dispersant is used in such a quantity that the resulting interparticle electrostatic repulsion counter-balances the interparticle van der Waals attraction. Investigation continues to determine the mechanisms of such excess energy dissipation under shear. New experimental results are presented in this report to verify the role of the anionic polymeric dispersant in such excess energy dissipation of CWS.

  6. [The role of additives in bio-mass coal briquette on sulfur retention enhancement].

    PubMed

    Lu, Yongqi; Xu, Kangfu; Ma, Yongliang; Wei, Tiejun; Hao, Jiming

    2002-01-30

    The research first conducted the sulfur-fixing experiment of bio-mass coal briquette in a tubular furnace. The impacts of three additives Al2O3, Fe2O3 and MnO2 on the sulfur retention by calcium-based sorbent in briquette were investigated, and only Al2O3 displayed the enhancement of sulfur retention. The TGA experiment was further carried out, and proved that the high-temperature decomposition of CaSO4 in the deoxidization atmosphere was effectively inhibited with the addition of Al2O3. The XPS and XRD analyses of briquette ash showed that due to the interaction among Al2O3, CaSO4 and CaO, the composite CaSO4.3CaO.3Al2O3 which has more thermal stability was formed. With its wrapping or binding onto the surface of CaSO4 crystal, the decomposition of CaSO4 was mitigated. PMID:11987400

  7. Attosecond Pulse Carrier-Envelope Phase Effects: Roles of Frequency, Intensity and an Additional IR Pulse

    NASA Astrophysics Data System (ADS)

    Pronin, Evgeny A.; Peng, Liang-You; Starace, Anthony F.

    2008-05-01

    The effects of the carrier-envelope phase (CEP) of a few-cycle attosecond pulse on ionized electron momentum and energy spectra are analyzed, both with and without an additional few-cycle IR pulse [1, 2]. In the absence of an IR pulse, the CEP-induced asymmetries in the ionized electron momentum distributions are shown to vary as the 3/2 power of the attosecond pulse intensity. These asymmetries are also found to satisfy an approximate scaling law involving the frequency and intensity of the attosecond pulse. In the presence of even a very weak IR pulse, the attosecond pulse CEP-induced asymmetries are found to be significantly augmented. In addition, for higher IR laser intensities, we observe for low electron energies peaks separated by the IR photon energy in one electron momentum direction along the laser polarization axis; in the opposite direction, we find structured peaks that are spaced by twice the IR photon energy. Possible physical mechanisms for such asymmetric, low-energy structures in the ionized electron momentum distribution are proposed. Our results are based on single-active-electron solutions of the 3D TDSE for H and He. [1] Peng LY, Pronin EA, and Starace AF, New J. Phys. 10, xxx (2008); [2] Peng LY, Starace AF, Phys. Rev. A 76, 043401 (2007)

  8. Role of Carbon-Addition and Hydrogen-Migration Reactions in Soot Surface Growth.

    PubMed

    Zhang, Hong-Bo; Hou, Dingyu; Law, Chung K; You, Xiaoqing

    2016-02-11

    Using density functional theory and master equation modeling, we have studied the kinetics of small unsaturated aliphatic molecules reacting with polycyclic aromatic hydrocarbon (PAH) molecules having a diradical character. We have found that these reactions follow the mechanism of carbon addition and hydrogen migration (CAHM) on both spin-triplet and open-shell singlet potential energy surfaces at a rate that is about ten times those of the hydrogen-abstraction-carbon-addition (HACA) reactions at 1500 K in the fuel-rich postflame region. The results also show that the most active reaction sites are in the center of the zigzag edges of the PAHs. Furthermore, the reaction products are more likely to form straight rather than branched aliphatic side chains in the case of reacting with diacetylene. The computed rate constants are also found to be independent of pressure at conditions of interest in soot formation, and the activation barriers of the CAHM reactions are linearly correlated with the diradical characters. PMID:26799641

  9. Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives — A Review

    PubMed Central

    Melo, A. D. B.; Silveira, H.; Luciano, F. B.; Andrade, C.; Costa, L. B.; Rostagno, M. H.

    2016-01-01

    The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP’s role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets. PMID:26732323

  10. Possible additional roles in mating for Ustilago maydis Rho1 and 14-3-3 homologues

    PubMed Central

    Pham, Cau D

    2010-01-01

    Both the Rho GTPases and 14-3-3 proteins each belong to ubiquitous families of proteins involved in a variety of cellular processes, including cytokinesis, cell polarity, cellular differentiation and apoptosis. In fungi, these components of signaling pathways are involved in cell cycle regulation, cytokinesis and virulence. We study cellular differentiation and pathogenesis for Ustilago maydis, the dimorphic fungal pathogen of maize. We have reported on the interactions of Pdc1, a U. maydis homologue of human 14-3-3ɛ, with Rho1, a small GTP binding protein; these proteins participate in cell polarity and filamentation pathways that include another small G protein, Rac1, and its effector PAK kinase, Cla4. Here we describe additional experiments that explore possible relationships of Pdc1 and Rho1 with another PAK-like kinase pathway and with the a matingtype locus. PMID:20539785

  11. Nutrition Metabolism Plays an Important Role in the Alternate Bearing of the Olive Tree (Olea europaea L.)

    PubMed Central

    Turktas, Mine; Inal, Behcet; Okay, Sezer; Erkilic, Emine Gulden; Dundar, Ekrem; Hernandez, Pilar; Dorado, Gabriel; Unver, Turgay

    2013-01-01

    The olive tree (Olea europaea L.) is widely known for its strong tendency for alternate bearing, which severely affects the fruit yield from year to year. Microarray based gene expression analysis using RNA from olive samples (on-off years leaves and ripe-unripe fruits) are particularly useful to understand the molecular mechanisms influencing the periodicity in the olive tree. Thus, we carried out genome wide transcriptome analyses involving different organs and temporal stages of the olive tree using the NimbleGen Array containing 136,628 oligonucleotide probe sets. Cluster analyses of the genes showed that cDNAs originated from different organs could be sorted into separate groups. The nutritional control had a particularly remarkable impact on the alternate bearing of olive, as shown by the differential expression of transcripts under different temporal phases and organs. Additionally, hormonal control and flowering processes also played important roles in this phenomenon. Our analyses provide further insights into the transcript changes between ”on year” and “off year” leaves along with the changes from unrpipe to ripe fruits, which shed light on the molecular mechanisms underlying the olive tree alternate bearing. These findings have important implications for the breeding and agriculture of the olive tree and other crops showing periodicity. To our knowledge, this is the first study reporting the development and use of an olive array to document the gene expression profiling associated with the alternate bearing in olive tree. PMID:23555820

  12. Macrophages as IL-25/IL-33-Responsive Cells Play an Important Role in the Induction of Type 2 Immunity

    PubMed Central

    Yang, Zhonghan; Grinchuk, Viktoriya; Urban, Joseph F.; Bohl, Jennifer; Sun, Rex; Notari, Luigi; Yan, Shu; Ramalingam, Thirumalai; Keegan, Achsah D.; Wynn, Thomas A.; Shea-Donohue, Terez; Zhao, Aiping

    2013-01-01

    Type 2 immunity is essential for host protection against nematode infection but is detrimental in allergic inflammation or asthma. There is a major research focus on the effector molecules and specific cell types involved in the initiation of type 2 immunity. Recent work has implicated an important role of epithelial-derived cytokines, IL-25 and IL-33, acting on innate immune cells that are believed to be the initial sources of type 2 cytokines IL-4/IL-5/IL-13. The identities of the cell types that mediate the effects of IL-25/IL-33, however, remain to be fully elucidated. In the present study, we demonstrate that macrophages as IL-25/IL-33-responsive cells play an important role in inducing type 2 immunity using both in vitro and in vivo approaches. Macrophages produced type 2 cytokines IL-5 and IL-13 in response to the stimulation of IL-25/IL-33 in vitro, or were the IL-13-producing cells in mice administrated with exogenous IL-33 or infected with Heligmosomoides bakeri. In addition, IL-33 induced alternative activation of macrophages primarily through autocrine IL-13 activating the IL-4Rα-STAT6 pathway. Moreover, depletion of macrophages attenuated the IL-25/IL-33-induced type 2 immunity in mice, while adoptive transfer of IL-33-activated macrophages into mice with a chronic Heligmosomoides bakeri infection induced worm expulsion accompanied by a potent type 2 protective immune response. Thus, macrophages represent a unique population of the innate immune cells pivotal to type 2 immunity and a potential therapeutic target in controlling type 2 immunity-mediated inflammatory pathologies. PMID:23536877

  13. A complex of Wiskott-Aldrich syndrome protein with mammalian verprolins plays an important role in monocyte chemotaxis.

    PubMed

    Tsuboi, Shigeru

    2006-06-01

    The Wiskott-Aldrich syndrome protein (WASP) is a product of the gene defective in an Xid disorder, Wiskott-Aldrich syndrome. WASP expression is limited to hemopoietic cells, and WASP regulates the actin cytoskeleton. It has been reported that monocytes/macrophages from WASP-deficient Wiskott-Aldrich syndrome patients are severely defective in chemotaxis, resulting in recurrent infection. However, the molecular basis of such chemotactic defects is not understood. Recently, the WASP N-terminal region was found to bind to the three mammalian verprolin homologs: WASP interacting protein (WIP); WIP and CR16 homologous protein (WICH)/WIP-related protein (WIRE); and CR16. Verprolin was originally found to play an important role in the regulation of actin cytoskeleton in yeast. We have shown that WASP, WIP, and WICH/WIRE are expressed predominantly in the human monocyte cell line THP-1 and that WIP and WICH/WIRE are involved in monocyte chemotaxis. When WASP binding to verprolins was blocked, chemotactic migration of monocytes was impaired in both THP-1 cells and primary human monocytes. Increased expression of WASP and WIP enhanced monocyte chemotaxis. Blocking WASP binding to verprolins impaired cell polarization but not actin polymerization. These results indicate that a complex of WASP with mammalian verprolins plays an important role in chemotaxis of monocytes. Our results suggest that WASP and mammalian verprolins function as a unit in monocyte chemotaxis and that the activity of this unit is critical to establish cell polarization. In addition, our results also indicate that the WASP-verprolin complex is involved in other functions such as podosome formation and phagocytosis. PMID:16709815

  14. Soil water content plays an important role in soil-atmosphere exchange of carbonyl sulfide (OCS)

    NASA Astrophysics Data System (ADS)

    Yi, Zhigang; Behrendt, Thomas; Bunk, Rüdiger; Wu, Dianming; Kesselmeier, Jürgen

    2016-04-01

    Carbonyl sulfide (OCS) is a quite stable gas in the troposphere and is transported up to the stratosphere, where it contributes to the sulfate aerosol layer (Crutzen 1976). The tropospheric concentration seems to be quite constant, indicating a balance between sinks and sources. Recent work by Sandoval-Soto et al. (2005) demonstrated the enormous strength of the vegetation sink and the urgent needs to understand the sinks and sources. The role of soils is a matter of discussion (Kesselmeier et al., 1999; Van Diest and Kesselmeier, 2008; Maseyk et al., 2014; Whelan et al., 2015). To better understand the influence of soil water content and OCS mixing ratio on OCS fluxes, we used an OCS analyzer (LGR COS/CO Analyzer 907-0028, Los Gatos, CA, USA) coupled with automated soil chamber system (Behrendt et al., 2014) to measure the OCS fluxes with a slow drying of four different types of soil (arable wheat soil in Mainz, blueberry soil in Waldstein, spruce soil in Waldstein and needle forest soil in Finland). Results showed that OCS fluxes as well as the optimum soil water content for OCS uptake varied significantly for different soils. The net production rates changed significantly with the soil drying out from 100% to about 5% water holding capacity (WHC), implying that soil water content play an important role in the uptake processes. The production and uptake processes were distinguished by the regression of OCS fluxes under different OCS mixing ratios. OCS compensation points (CP) were found to differ significantly for different soil types and water content, with the lowest CP at about 20% WHC, implying that when estimating the global budgets of OCS, especially for soils fluxes, soil water content should be taken into serious consideration. References Crutzen, P. J. 1976, Geophys. Res. Lett., 3, 73-76. Sandoval-Soto, L. et al., 2005, Biogeosciences, 2, 125-132. Kesselmeier, J. et al., 1999, J. Geophys. Res., 104, 11577-11584. Van Diest, H. and Kesselmeier, J. 2008

  15. Mechanisms of silver nanoparticle-induced toxicity and important role of autophagy.

    PubMed

    Mao, Bin-Hsu; Tsai, Jui-Chen; Chen, Chun-Wan; Yan, Shian-Jang; Wang, Ying-Jan

    2016-10-01

    Safety concerns have been raised over the extensive applications of silver nanoparticles (AgNPs) because nano dimensions make them highly bioactive, being potentially harmful to the exposed humans. Surface physico-chemistry (shape, surface charge, chemical composition, etc.) that mainly dictates nano-bio interactions is relevant for influencing their biocompatibility and toxicity. Although the hazardousness of AgNPs has been demonstrated in vitro and in vivo, mechanistic understanding of the toxicity particularly at the molecular and organismal levels, in addition to oxidative stress and silver ion dissolution, has remained unclear. A growing body of research has elucidated that autophagy, being activated in response to exposure to various nanomaterials, may serve as a cellular defense mechanism against nanotoxicity. Recently, autophagy activation was shown to correlate with AgNPs exposure; however, the subsequent autophagosome-lysosome fusion was defective. As autophagy plays a crucial role in selective removal of stress-mediated protein aggregates and injured organelles, AgNPs-induced autophagic flux defect may consequently lead to aggravated cytotoxic responses. Furthermore, we suggest that p62 accumulation resulting from defective autophagy may also potentially account for AgNPs cytotoxicity. Intriguingly, AgNPs have been shown to interfere with ubiquitin modifications, either via upregulating levels of enzymes participating in ubiquitination, or through impairing the biological reactivity of ubiquitin (due to formation of AgNPs-ubiquitin corona). Ubiquitination both confers selectivity to autophagy as well as modulates stabilization, activation, and trafficking of proteins involved in autophagic clearance pathways. In this regard, we offer a new perspective that interference of AgNPs with ubiquitination may account for AgNPs-induced defective autophagy and cytotoxic effects. PMID:27240148

  16. Incorporating clonal growth form clarifies the role of plant height in response to nitrogen addition.

    PubMed

    Gough, Laura; Gross, Katherine L; Cleland, Elsa E; Clark, Christopher M; Collins, Scott L; Fargione, Joseph E; Pennings, Steven C; Suding, Katharine N

    2012-08-01

    Nutrient addition to grasslands consistently causes species richness declines and productivity increases. Competition, particularly for light, is often assumed to produce this result. Using a long-term dataset from North American herbaceous plant communities, we tested whether height and clonal growth form together predict responses to fertilization because neither trait alone predicted species loss in a previous analysis. Species with a tall-runner growth form commonly increased in relative abundance in response to added nitrogen, while short species and those with a tall-clumped clonal growth form often decreased. The ability to increase in size via vegetative spread across space, while simultaneously occupying the canopy, conferred competitive advantage, although typically only the abundance of a single species within each height-clonal growth form significantly responded to fertilization in each experiment. Classifying species on the basis of two traits (height and clonal growth form) increases our ability to predict species responses to fertilization compared to either trait alone in predominantly herbaceous plant communities. Electronic supplementary material The online version of this article (doi:10.1007/s00442-012-2264-5) contains supplementary material, which is available to authorized users. PMID:22302512

  17. The role and future of the Laser Technology in the Additive Manufacturing environment

    NASA Astrophysics Data System (ADS)

    Levy, Gideon N.

    The Additive Manufacturing (AM) was, in the early days, strongly inspired by upcoming laser technologies. The trend to apply lasers in manufacturing in the 1970's might be also be seen as the ignition point, as is evident in early precedent patents. During the evolvement of AM processes, many new systems based on various physical principals were evident; alternative energy sources for AM are in use today. Starting with the 'historical' background followed by a detailed classification analyzing the enablers in use, relevant laser technologies have been identified. This paper focuses on powder bed technologies for plastics and metals as the relevant Laser technology. It concentrates on laser influences and state-of-the-art knowledge. The paper will present a generalized, 'big picture' overview indicating 'lessons learned' and where future emphasis should be focused. Opportunities and challenges, including actual development status, will be described in view of the desired outcomes. Finally, future research challenges and conclusions will be stated and several relevant references for further readings will be given.

  18. The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases

    PubMed Central

    Rižner, Tea Lanišnik

    2016-01-01

    Gynecological diseases such as endometriosis, adenomyosis and uterine fibroids, and gynecological cancers including endometrial cancer and ovarian cancer, affect a large proportion of women. These diseases are estrogen dependent, and their progression often depends on local estrogen formation. In peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3β-hydroxysteroid dehydrogenase-Δ4-isomerase, aromatase, and 17-ketosteroid reductase. This review introduces the sulfatase and sulfotransferase enzymes, in terms of their structures and reaction mechanisms, and the regulation and different transcripts of their genes, together with the importance of their currently known single nucleotide polymorphisms. Data on expression of sulfatase and sulfotransferases in gynecological diseases are also reviewed. There are often unchanged mRNA and protein levels in diseased tissue, with higher sulfatase activities in cancerous endometrium, ovarian cancer cell lines, and adenomyosis. This can be indicative of a disturbed balance between the sulfatase and sulfotransferases enzymes, defining the potential for sulfatase as a drug target for treatment of gynecological diseases. Finally, clinical trials with sulfatase inhibitors are discussed, where two inhibitors have already concluded phase II trials, although so far with no convincing clinical outcomes for patients with endometrial cancer and endometriosis. PMID:26924986

  19. Basal transcription factor 3 plays an important role in seed germination and seedling growth of rice.

    PubMed

    Wang, Wenyi; Xu, Mengyun; Wang, Ya; Jamil, Muhammad

    2014-01-01

    BTF3 has been recognized to be involved in plant growth and development. But its function remains mostly unknown during seed germination and seedling stage. Here, we have analyzed OsBTF3-related sequences in Oryza sativa L. subspecies, japonica, which resembles with the conserved domain of a nascent polypeptide associated complex (NAC) with different homologs of OsBTF3 and human BTF3. Inhibition of Osj10gBTF3 has led to considerable morphological changes during seed germination and seedling growth. Germination percentage was not influenced by the application of GA3, ABA, and NaCl but all concentrations caused wild-type (WT) seeds to germinate more rapidly than the RNAi (Osj10gBTF3 (Ri)) transgenic lines. Seedling inhibition was more severe in the Osj10gBTF3 (Ri) seedlings compared with their WT especially when treated with 100 or 200 μM GA3; 50% reduction in shoots was observed in Osj10gBTF3 (Ri) seedlings. The expression of Osj3g1BTF3, Osj3g2BTF3 and Osj10gBTF3 was primarily constitutive and generally modulated by NaCl, ABA, and GA3 stresses in both Osj10gBTF3 (Ri) lines and WT at the early seedling stage, suggesting that Osj3g1BTF3 and Osj10gBTF3 are much similar but different from Osj3g2BTF3 in biological function. These results show that OsBTF3 plays an important role in seed germination and seedling growth gives a new perception demonstrating that more multifaceted regulatory functions are linked with BTF3 in plants. PMID:24971328

  20. Scutellarin’s Cardiovascular Endothelium Protective Mechanism: Important Role of PKG-Iα

    PubMed Central

    Chen, Chen; Yang, Jian; Li, Jiaxun; Hu, Na; Li, Yang; Zhang, Dongmei; Guo, Tao; Liu, Xuan; Yang, Weimin

    2015-01-01

    Scutellarin (SCU), a flavonoid glycoside compound, has been successfully used in clinic for treatment of ischemic diseases in China. In this report, we checked the effects of SCU on endothelium dysfunction (ED) of coronary artery (CA) against myocardial ischemia reperfusion (MIR) injury in vivo. The involvement of PKG-Iα was further studied using cultured endothelial cells subjected to hypoxia reoxygenation (HR) injury in vitro. In rat MIR model, SCU (45 and 90 mg/kg, iv) significantly reduced ischemic size and restored the endothelium-dependent vasodilation of isolated CA rings. PKG inhibitor Rp-8-Br-cGMP (50 μg/kg, iv) could ameliorate the protective effects of SCU. Increase in phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a main substrate of PKG, at Ser 239 was observed in both heart tissue and serum of SCU-treated animals. In cultured human cardiac microvascular endothelial cells (HCMECs), SCU (1 and 10 μM) dose-dependently protected cell viability and increased the mRNA and protein level of PKG-Iα against HR injury. The activity of PKG was also increased by SCU treatment. The activation of PKG–1α was then studied using targeted proteomic analysis (MRM-MS) checking the phosphorylation state of the autophosphorylation domain (aa42-94). Significant decrease in phosphorylation of PKG-Iα at Ser50, Ser72, Ser89 was induced by HR injury while SCU treatment significantly increased the phosphorylation of PKG-Iα, not only at Ser50, Ser72 and Ser89, but also at Ser44 and Thr58 (two novel phosphorylation domains). Our results demonstrate PKG-Iα might play an important role in the protective effects of SCU on ED against MIR injury. PMID:26440524

  1. Transposable elements play an important role during cotton genome evolution and fiber cell development.

    PubMed

    Wang, Kun; Huang, Gai; Zhu, Yuxian

    2016-02-01

    Transposable elements (TEs) usually occupy largest fractions of plant genome and are also the most variable part of the structure. Although traditionally it is hallmarked as "junk and selfish DNA", today more and more evidence points out TE's participation in gene regulations including gene mutation, duplication, movement and novel gene creation via genetic and epigenetic mechanisms. The recently sequenced genomes of diploid cottons Gossypium arboreum (AA) and Gossypium raimondii (DD) together with their allotetraploid progeny Gossypium hirsutum (AtAtDtDt) provides a unique opportunity to compare genome variations in the Gossypium genus and to analyze the functions of TEs during its evolution. TEs accounted for 57%, 68.5% and 67.2%, respectively in DD, AA and AtAtDtDt genomes. The 1,694 Mb A-genome was found to harbor more LTR(long terminal repeat)-type retrotransposons that made cardinal contributions to the twofold increase in its genome size after evolution from the 775.2 Mb D-genome. Although the 2,173 Mb AtAtDtDt genome showed similar TE content to the A-genome, the total numbers of LTR-gypsy and LTR-copia type TEs varied significantly between these two genomes. Considering their roles on rewiring gene regulatory networks, we believe that TEs may somehow be involved in cotton fiber cell development. Indeed, the insertion or deletion of different TEs in the upstream region of two important transcription factor genes in At or Dt subgenomes resulted in qualitative differences in target gene expression. We suggest that our findings may open a window for improving cotton agronomic traits by editing TE activities. PMID:26687725

  2. The Important Roles of Steroid Sulfatase and Sulfotransferases in Gynecological Diseases.

    PubMed

    Rižner, Tea Lanišnik

    2016-01-01

    Gynecological diseases such as endometriosis, adenomyosis and uterine fibroids, and gynecological cancers including endometrial cancer and ovarian cancer, affect a large proportion of women. These diseases are estrogen dependent, and their progression often depends on local estrogen formation. In peripheral tissues, estrogens can be formed from the inactive precursors dehydroepiandrosterone sulfate and estrone sulfate. Sulfatase and sulfotransferases have pivotal roles in these processes, where sulfatase hydrolyzes estrone sulfate to estrone, and dehydroepiandrosterone sulfate to dehydroepiandrosterone, and sulfotransferases catalyze the reverse reactions. Further activation of estrone to the most potent estrogen, estradiol, is catalyzed by 17-ketosteroid reductases, while estradiol can also be formed from dehydroepiandrosterone by the sequential actions of 3β-hydroxysteroid dehydrogenase-Δ(4)-isomerase, aromatase, and 17-ketosteroid reductase. This review introduces the sulfatase and sulfotransferase enzymes, in terms of their structures and reaction mechanisms, and the regulation and different transcripts of their genes, together with the importance of their currently known single nucleotide polymorphisms. Data on expression of sulfatase and sulfotransferases in gynecological diseases are also reviewed. There are often unchanged mRNA and protein levels in diseased tissue, with higher sulfatase activities in cancerous endometrium, ovarian cancer cell lines, and adenomyosis. This can be indicative of a disturbed balance between the sulfatase and sulfotransferases enzymes, defining the potential for sulfatase as a drug target for treatment of gynecological diseases. Finally, clinical trials with sulfatase inhibitors are discussed, where two inhibitors have already concluded phase II trials, although so far with no convincing clinical outcomes for patients with endometrial cancer and endometriosis. PMID:26924986

  3. Grandparenting and well-being: How important is grandparent-role centrality?

    PubMed Central

    Muller, Ziva; Litwin, Howard

    2014-01-01

    Objectives The purpose of the study was to examine the association between the centrality of the grandparent’s role and well-being in the population of European grandparents, aged 50 and older. Method The study was a secondary analysis of data gathered in the first wave of the Survey of Health, Ageing and Retirement in Europe (SHARE). The sample included grandparents who looked after their grandchildren without the presence of the parents (n=3,888). Respondents’ scores on the CES-D Depression Scale were regressed on the frequency of contact with grandchildren, beliefs and attitudes about grandparenting and grandparent-focused role occupancy, and on a composite measure of grandparent-role centrality, controlling for age, gender, education, household income, physical status and country. Results The findings negated the hypothesized positive association between grandparent-role centrality and well-being. Only one of the three indices of grandparenthood was related to well being when background and health variables were taken into account. The related aspect—grandparent-focused role occupancy—was positively associated with depressive symptoms. Conclusion the study refutes the central claim of role theory according to which salient roles are more beneficial to the psychological well-being of the individual than are other roles, especially in old age. It also questions the theoretical framework of grandparent role meaning that is commonly cited in the literature. PMID:25400536

  4. Does release of encapsulated nutrients have an important role in the efficacy of xylanase in broilers?

    PubMed

    Khadem, A; Lourenço, M; Delezie, E; Maertens, L; Goderis, A; Mombaerts, R; Höfte, M; Eeckhaut, V; Van Immerseel, F; Janssens, G P J

    2016-05-01

    The non-starch polysaccharides (NSPs) in cell walls can act as a barrier for digestion of intracellular nutrients. This effect is called "cage effect." Part of the success of fibrolytic enzymes in broiler feed is assumed to be attributed to cage effect reduction. Further, changes in viscosity and potential prebiotic action should also be considered. The aim of this study was to gain insight into the relative importance of the cage effect in xylanase efficacy in broilers. Using a 2×2 factorial design, 24 pens with 30 Ross 308 male chicks were fed corn-soy based diets consisting of normal and freeze-thawed (5 d at -18°C) corn, both with and without xylanase. The freeze-thaw method was used to eliminate the cage effect, whereas a corn-based diet was used to exclude viscosity effects. Body weights (BW), feed intake (FI), and feed conversion ratio (FCR) were determined at d 13, 26, and 39. A balance study was executed at the end of the growing phase. These birds were euthanized at d 34 (non-fasted) to determine the viscosity of digesta, blood metabolites, intestinal morphology, and microbiota composition. During the finisher period, there was a significant interaction between enzyme supplementation and freeze-thawing for FCR, in which FCR was improved by freeze-thawed corn and tended to be improved by normal corn+enzyme compared with the control group. The improvement in performance (finisher period) of freeze-thawed corn and xylanase coincided with increased gut absorption of glucose (based on postprandial plasma concentrations) and increased number of Clostridiumcluster IV in the caecum, and agreed with the higher gut villus height. In addition, xylanase inclusion significantly increased the postprandial plasma glycine and triglycerides concentration, and led to elevated bacterial gene copies of butyryl CoA:acetate CoA-transferase, suggesting a prebiotic effect of xylanase addition through more than just the cage effect reduction. The applied model managed to rule

  5. Sex and Sex-Role Identification: An Important Distinction for Organizational Research.

    ERIC Educational Resources Information Center

    Powell, Gary N.; Butterfield, R. Anthony

    Studies which have investigated males' and females' attitudes and behavior in organizations have yielded apparently contradictory results. In some studies, individuals have followed traditional sex-role stereotypes; in others, they have not. A proposed explanation for these inconsistencies is that sex-role identification is a more important…

  6. The origin of aromaticity: important role of the sigma framework in benzene.

    PubMed

    Kovacević, Borislav; Barić, Danijela; Maksić, Zvonimir B; Müller, Thomas

    2004-09-20

    The physical nature of aromaticity is addressed at a high ab initio level. It is conclusively shown that the extrinsic aromatic stabilization energy of benzene E(ease)B, estimated relative to its linear polyene counterpart(s), is very well-reproduced at the Hartree-Fock (HF) level. This is a consequence of the fact that the contributions arising from the zero-point vibrational energy (ZPVE) and electron correlation are rather small. More specifically, they yield together 2.0 kcalmol(-1) to the destabilization of benzene. A careful scrutiny of the HF energies by virial theorem shows further that the kinetic energies of the sigma and pi electrons E(T)HF(sigma) and E(T)HF(pi) are strictly additive in the gauge linear zig-zag polyenes, which also holds for their sum Et(T)HF This finding has the important corollary that E(ease)B is little dependent on the choice of the homodesmic reactions involving zig-zag polyenes. A detailed physical analysis of the sigma- and pi-electron contributions to extrinsic aromaticity requires explicit introduction of the potential energy terms Vne, Vee, and Vnn, which signify Coulomb interactions between the electrons and the nuclei. The Vee term involves repulsive interaction Vee(sigmapi) between the sigma and pi electrons, which cannot be unequivocally resolved into sigma and pi contributions. The same holds for the Vnn energy, which implicitly depends on the electron density distribution via the Born-Oppenheimer (BO) potential energy surface. Several possibilities for partitioning Vee(sigmapi) and Vnn terms into sigma and pi components are examined. It is argued that the stockholder principle is the most realistic, which strongly indicates that E(ease)B is a result of favorable sigma-framework interactions. In contrast, the pi-electron framework prefers the open-chain linear polyenes. PMID:15503393

  7. NAC transcription factors play an important role in ethylene biosynthesis, reception and signaling of tomato fruit ripening.

    PubMed

    Kou, Xiaohong; Liu, Chen; Han, Lihua; Wang, Shuang; Xue, Zhaohui

    2016-06-01

    NAC proteins comprise a large family of transcription factors that play important roles in diverse physiological processes during development. To explore the role of NAC transcription factors in the ripening of fruits, we predicted the secondary and tertiary structure as well as regulative function of the SNAC4 (SlNAC48, Accession number: NM 001279348.2) and SNAC9 (SlNAC19, Accession number: XM 004236996.2) transcription factors in tomato. We found that the tertiary structure of SNAC9 was similar to that of ATNAP, which played an important role in the fruit senescence and was required for ethylene stimulation. Likewise, the bio-function prediction results indicated that SNAC4 and SNAC9 participated in various plant hormone signaling and senescence processes. More information about SNACs was obtained by the application of VIGS (virus-induced gene silencing). The silencing of SNAC4 and SNAC9 dramatically repressed the LeACS2, LeACS4 and LeACO1 expression, which consequently led to the inhibition of the ripening process. The silencing of SNACs down-regulated the mRNA levels of the ethylene perception genes and, at the same time, suppressed the expression of ethylene signaling-related genes except for LeERF2 which was induced by the silencing of SNAC4. The expressions of LeRIN were different in two silenced fruits. In addition, the silencing of SNAC4 reduced its mRNA level, while the silencing of SNAC9 induced its expression. Furthermore, the silencing of LeACS4, LeACO1 and LeERF2 reduced the expression of SNAC4 and SNAC9, while the silencing of NR induced the expression of all of them. In particular, these results indicate that SNAC transcription factors bind to the promoter of the ethylene synthesis genes in vitro. This experimental evidence demonstrates that SNAC4 and SNAC9 could positively regulate the tomato fruit ripening process by functioning upstream of ethylene synthesis genes. These outcomes will be helpful to provide a theoretical foundation for further

  8. Importance of choline as essential nutrient and its role in prevention of various toxicities.

    PubMed

    Biswas, Somava; Giri, Sarbani

    2015-01-01

    Choline is a water-soluble essential nutrient included as a member of the vitamin B12 group owing to its structural similarities with that of the other members of the group. Its roles and functions, however, extend much wider than that of the vitamins with which it is grouped. Choline is vital for maintenance of various key metabolic processes which play a role in the prevention or progression of various health impairments. The occurrence of diseases like neural tube defect (NTD) and Alzheimer's is prevented by the metabolic role of choline. It is also indispensable for mitigation of various forms of toxic contamination. While adequate level of choline in the body is essential, an excess of choline can result in various forms of disorder. To maintain the optimal level of choline in the body can be a challenge. The vital roles played by choline together with the range of contradictions and problems that choline presents make choline an interesting area of study. This paper attempts to summarize and review some recent publications on choline that have opened up new prospect in understanding the multiple role played by choline and in throwing light on the role played by this wonder essential nutrient in mitigating various forms of toxic contamination. PMID:25923965

  9. Mycobacterial Pan-Genome Analysis Suggests Important Role of Plasmids in the Radiation of Type VII Secretion Systems

    PubMed Central

    Dumas, Emilie; Christina Boritsch, Eva; Vandenbogaert, Mathias; Rodríguez de la Vega, Ricardo C.; Thiberge, Jean-Michel; Caro, Valerie; Gaillard, Jean-Louis; Heym, Beate; Girard-Misguich, Fabienne; Brosch, Roland; Sapriel, Guillaume

    2016-01-01

    In mycobacteria, various type VII secretion systems corresponding to different ESX (ESAT-6 secretory) types, are contributing to pathogenicity, iron acquisition, and/or conjugation. In addition to the known chromosomal ESX loci, the existence of plasmid-encoded ESX systems was recently reported. To investigate the potential role of ESX-encoding plasmids on mycobacterial evolution, we analyzed a large representative collection of mycobacterial genomes, including both chromosomal and plasmid-borne sequences. Data obtained for chromosomal ESX loci confirmed the previous five classical ESX types and identified a novel mycobacterial ESX-4-like type, termed ESX-4-bis. Moreover, analysis of the plasmid-encoded ESX loci showed extensive diversification, with at least seven new ESX profiles, identified. Three of them (ESX-P clusters 1–3) were found in multiple plasmids, while four corresponded to singletons. Our phylogenetic and gene-order-analyses revealed two main groups of ESX types: 1) ancestral types, including ESX-4 and ESX-4-like systems from mycobacterial and non-mycobacterial actinobacteria and 2) mycobacteria-specific ESX systems, including ESX-1-2-3-5 systems and the plasmid-encoded ESX types. Synteny analysis revealed that ESX-P systems are part of phylogenetic groups that derived from a common ancestor, which diversified and resulted in the different ESX types through extensive gene rearrangements. A converging body of evidence, derived from composition bias-, phylogenetic-, and synteny analyses points to a scenario in which ESX-encoding plasmids have been a major driving force for acquisition and diversification of type VII systems in mycobacteria, which likely played (and possibly still play) important roles in the adaptation to new environments and hosts during evolution of mycobacterial pathogenesis. PMID:26748339

  10. Diversity and distribution of transcription factors: their partner domains play an important role in regulatory plasticity in bacteria.

    PubMed

    Rivera-Gómez, Nancy; Segovia, Lorenzo; Pérez-Rueda, Ernesto

    2011-08-01

    The ability of bacteria to deal with diverse environmental changes depends on their repertoire of genes and their ability to regulate their expression. In this process, DNA-binding transcription factors (TFs) have a fundamental role because they affect gene expression positively and/or negatively depending on operator context and ligand-binding status. Here, we show an exhaustive analysis of winged helix-turn-helix domains (wHTHs), a class of DNA-binding TFs. These proteins were identified in high proportions and widely distributed in bacteria, representing around half of the total TFs identified so far. In addition, we evaluated the repertoire of wHTHs in terms of their partner domains (PaDos), identifying a similar trend, as with TFs, i.e. they are abundant and widely distributed in bacteria. Based on the PaDos, we defined three main groups of families: (i) monolithic, those families with little PaDo diversity, such as LysR; (ii) promiscuous, those families with a high PaDo diversity; and (iii) monodomain, with families of small sizes, such as MarR. These findings suggest that PaDos have a very important role in the diversification of regulatory responses in bacteria, probably contributing to their regulatory complexity. Thus, the TFs discriminate over longer regions on the DNA through their diverse DNA-binding domains. On the other hand, the PaDos would allow a great flexibility for transcriptional regulation due to their ability to sense diverse stimuli through a variety of ligand-binding compounds. PMID:21636649

  11. Mycobacterial Pan-Genome Analysis Suggests Important Role of Plasmids in the Radiation of Type VII Secretion Systems.

    PubMed

    Dumas, Emilie; Christina Boritsch, Eva; Vandenbogaert, Mathias; Rodríguez de la Vega, Ricardo C; Thiberge, Jean-Michel; Caro, Valerie; Gaillard, Jean-Louis; Heym, Beate; Girard-Misguich, Fabienne; Brosch, Roland; Sapriel, Guillaume

    2016-02-01

    In mycobacteria, various type VII secretion systems corresponding to different ESX (ESAT-6 secretory) types, are contributing to pathogenicity, iron acquisition, and/or conjugation. In addition to the known chromosomal ESX loci, the existence of plasmid-encoded ESX systems was recently reported. To investigate the potential role of ESX-encoding plasmids on mycobacterial evolution, we analyzed a large representative collection of mycobacterial genomes, including both chromosomal and plasmid-borne sequences. Data obtained for chromosomal ESX loci confirmed the previous five classical ESX types and identified a novel mycobacterial ESX-4-like type, termed ESX-4-bis. Moreover, analysis of the plasmid-encoded ESX loci showed extensive diversification, with at least seven new ESX profiles, identified. Three of them (ESX-P clusters 1-3) were found in multiple plasmids, while four corresponded to singletons. Our phylogenetic and gene-order-analyses revealed two main groups of ESX types: 1) ancestral types, including ESX-4 and ESX-4-like systems from mycobacterial and non-mycobacterial actinobacteria and 2) mycobacteria-specific ESX systems, including ESX-1-2-3-5 systems and the plasmid-encoded ESX types. Synteny analysis revealed that ESX-P systems are part of phylogenetic groups that derived from a common ancestor, which diversified and resulted in the different ESX types through extensive gene rearrangements. A converging body of evidence, derived from composition bias-, phylogenetic-, and synteny analyses points to a scenario in which ESX-encoding plasmids have been a major driving force for acquisition and diversification of type VII systems in mycobacteria, which likely played (and possibly still play) important roles in the adaptation to new environments and hosts during evolution of mycobacterial pathogenesis. PMID:26748339

  12. Effect on Public Policy from Macro to Nano Aspects of the Deadliest Illness of Mankind: Important Role of Physics

    NASA Astrophysics Data System (ADS)

    Saxena, Arjun

    2013-04-01

    The effect on public policy of macro to nano aspects of the deadliest Illness known to mankind is given. The focus is on the important role of physics which has been ignored so far to solve its problems. It is now acknowledged that the deadliest illness is actually a group of illnesses which are lumped together as mental illnesses. They are the most widespread and damaging illnesses in the world. Their impact on the entire society globally is huge because they afflict majority of the people irrespective of race, religion, sex, age, education and economic status. In USA alone, the number afflicted according to the official count is about 80 million (out of a total population of 315 million), and it is projected to increase to about 25 to 30% of the population within two decades. A model is given in this paper to address some of the key issues from macro to nano aspects of the deadliest illness. The information given in this paper is scientific though easy to understand. It will help the elected policy makers, public, physicists, neuroscientists, doctors, and care giving personnel world wide. The model explains the missing links in the diagnosis and treatment of mental illnesses. Additional evidence from other recent studies shall also be given.

  13. Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme.

    PubMed

    Naselli, Flores; Catanzaro, Irene; Bellavia, Daniele; Perez, Alessandro; Sposito, Laura; Caradonna, Fabio

    2014-02-15

    Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and methylation of sites contained in the 5' flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associated with the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentially influenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed a greater expression inhibition (ranging from 20% to 30%) compared with others carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an increase of expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 alleles play a more important role in the expression of the enzyme, compared with other (epi)genetic factors, since they are binding sites for trans-acting proteins. PMID:24333271

  14. An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib

    PubMed Central

    Kwon, Taeho; Kyung Rho, Jin; Cheol Lee, Jae; Park, Young-Ho; Shin, Hye-Jun; Cho, Sunwha; Kang, Yong-Kook; Kim, Bo-Yeon; Yoon, Do-Young; Yu, Dae-Yeul

    2015-01-01

    Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells. PMID:26021759

  15. Haemostatic role of intermediate filaments in adhered platelets: importance of the membranous system stability.

    PubMed

    Cerecedo, Doris; Martínez-Vieyra, Ivette; Mondragón, Ricardo; Mondragón, Mónica; González, Sirenia; Galván, Iván J

    2013-09-01

    The role of platelets in coagulation and the haemostatic process was initially suggested two centuries ago, and under appropriate physiological stimuli, these undergo abrupt morphological changes, attaching and spreading on damaged endothelium, preventing bleeding. During the adhesion process, platelet cytoskeleton reorganizes generating compartments in which actin filaments, microtubules, and associated proteins are arranged in characteristic patterns mediating crucial events, such as centralization of their organelles, secretion of granule contents, aggregation with one another to form a haemostatic plug, and retraction of these aggregates. However, the role of Intermediate filaments during the platelet adhesion process has not been explored. J. Cell. Biochem. 114: 2050-2060, 2013. © 2013 Wiley Periodicals, Inc. PMID:23553987

  16. Role of Academic Self-Efficacy in Moderating the Relation between Task Importance and Test Anxiety

    ERIC Educational Resources Information Center

    Nie, Youyan; Lau, Shun; Liau, Albert K.

    2011-01-01

    Emphasizing task importance, which is regarded as a way of motivating engaged behavior, may increase an individual's anxiety. The present research investigated whether academic self-efficacy could moderate the maladaptive relation between task importance and test anxiety. 1978 and 1670 Grade 9 Singaporean students participated in a survey related…

  17. The Role of Goal Importance in Predicting University Students' High Academic Performance

    ERIC Educational Resources Information Center

    Kyle, Vanessa A.; White, Katherine M.; Hyde, Melissa K.; Occhipinti, Stefano

    2014-01-01

    We examined goal importance, focusing on high, but not exclusive priority goals, in the theory of planned behaviour (TPB) to predict students' academic performance. At the beginning of semester, students in a psychology subject (N = 197) completed TPB and goal importance items for achieving a high grade. Regression analyses revealed partial…

  18. The mechanism of alkene addition to a nickel bis(dithiolene) complex: the role of the reduced metal complex.

    PubMed

    Dang, Li; Shibl, Mohamed F; Yang, Xinzheng; Alak, Aiman; Harrison, Daniel J; Fekl, Ulrich; Brothers, Edward N; Hall, Michael B

    2012-03-14

    The binding of an alkene by Ni(tfd)(2) [tfd = S(2)C(2)(CF(3))(2)] is one of the most intriguing ligand-based reactions. In the presence of the anionic, reduced metal complex, the primary product is an interligand adduct, while in the absence of the anion, dihydrodithiins and metal complex decomposition products are preferred. New kinetic (global analysis) and computational (DFT) data explain the crucial role of the anion in suppressing decomposition and catalyzing the formation of the interligand product through a dimetallic complex that appears to catalyze alkene addition across the Ni-S bond, leading to a lower barrier for the interligand adduct. PMID:22364208

  19. Does Morphology Play an Important Role in L2 Chinese Vocabulary Acquisition?

    ERIC Educational Resources Information Center

    Zhang, Haomin

    2016-01-01

    The present study examined the role of morphological awareness in second language (L2) Chinese vocabulary acquisition through an investigation of linguistic universality and specificity underlying morphological awareness. Morphological awareness in this study was conceptualized as a universal and sharable cognitive resource as well as a…

  20. Causal Models of Role Stressor Antecedents and Consequences: The Importance of Occupational Differences.

    ERIC Educational Resources Information Center

    Bacharach, Samuel; Bamberger, Peter

    1992-01-01

    Survey data from 215 nurses (10 male) and 430 civil engineers (10 female) supported the plausibility of occupation-specific models (positing direct paths between role stressors, antecedents, and consequences) compared to generic models. A weakness of generic models is the tendency to ignore differences in occupational structure and culture. (SK)

  1. Developing Future Women Leaders: The Importance of Mentoring and Role Modeling in the Girls' School Context

    ERIC Educational Resources Information Center

    Archard, Nicole

    2012-01-01

    In this article, I explore the concepts of mentoring and role modeling with regard to developing student leaders within the girls' school context. The foundation for this discussion lies in two qualitative studies involving staff and students from girls' schools located in Australia, New Zealand, and South Africa. Both survey and focus groups were…

  2. Segregation in Charter Schools: The Important Role of University-Based Authorizers

    ERIC Educational Resources Information Center

    Eckes, Suzanne E.; Plucker, Jonathan A.

    2013-01-01

    This article argues that one possible avenue for addressing and increasing student body diversity in charter schools may lie with the authorizer. In particular, we focus on the role of university-based authorizers, a group of sponsors that would appear to be especially concerned with educational opportunity given their faculties' traditional…

  3. Role of Y{sub 2}O{sub 3}, CaO, MgO additives on structural and microstructural behavior of zirconia/mullite aggregates

    SciTech Connect

    Mishra, D. K.; Prusty, Sasmita; Mohapatra, B. K.; Singh, S. K.; Behera, S. N.

    2012-07-23

    Zirconia mullite (MUZ), Y{sub 2}O{sub 3}-MUZ, CaO-MUZ and MgO-MUZ composites, synthesized through plasma fusion technique, are becoming important due to their commercial scale of production within five minutes of plasma treatment from sillimanite, zircon and alumina mixture. The X-ray diffraction studies reveal the monoclinic zirconia phase in MUZ composite whereas mixed monoclinic, tetragonal and cubic phases of zirconia have been observed in Y{sub 2}O{sub 3}, CaO, MgO added MUZ composites. The Y{sub 2}O{sub 3}, CaO and MgO additives act as sintering aids to favour the transformation and stabilisation of tetragonal and cubic zirconia phases at room temperature. These additives also play a key role in the development of various forms of microstructure to achieve dense MUZ composites.

  4. Role of Echocardiography in the Evaluation of Left Ventricular Assist Devices: the Importance of Emerging Technologies.

    PubMed

    Longobardo, Luca; Kramer, Christopher; Carerj, Scipione; Zito, Concetta; Jain, Renuka; Suma, Valentin; Thohan, Vinay; Sulemanjee, Nasir; Downey, Frank X; Khandheria, Bijoy K

    2016-07-01

    The role of left ventricular assist devices (LVAD) in patients with end-stage heart failure is well known, both as a temporary treatment before transplantation and as destination therapy, in a scenario of a relative shortage of donors to satisfy the increasing requests for transplantation. The increased population of LVAD patients needs careful imaging assessment before, during, and after LVAD implantation; echocardiography is the best tool for their evaluation and is considered the diagnostic technique of choice for the assessment before, during, and after device implantation. Although the conventional echocardiographic assessment is quite effective in evaluating the main critical issues, the role of new technologies like three-dimensional echocardiography and myocardial deformation measurements is still not properly clarified. In this review, we aim to provide an overview of the main elements that should be considered in the assessment of these patients, underlining the role that could be played by new techniques to improve the diagnostic and prognostic effectiveness of echocardiography in this setting. PMID:27216842

  5. The ZupT transporter plays an important role in zinc homeostasis and contributes to Salmonella enterica virulence

    PubMed Central

    Cerasi, Mauro; Liu, Janet Z.; Ammendola, Serena; Poe, Adam J.; Petrarca, Patrizia; Pesciaroli, Michele; Pasquali, Paolo; Raffatellu, Manuela; Battistoni, Andrea

    2014-01-01

    Zinc is an essential metal for cellular homeostasis and function in both eukaryotes and prokaryotes. To acquire this essential nutrient, bacteria employ transporters characterized by different affinity for the metal. Several studies have investigated the role of the high affinity transporter ZnuABC in the bacterial response to zinc shortage, showing that this transporter has a key role in adapting bacteria to zinc starvation. In contrast, the role of the low affinity zinc importer ZupT has been the object of limited investigations. Here we show that a Salmonella strain lacking ZupT is impaired in its ability to grow in metal devoid environments and that a znuABC zupT strain exhibits a severe growth defect in zinc devoid media, is hypersensitive to oxidative stress and contains reduced level of intracellular free zinc. Moreover, we show that ZupT plays a role also in the ability of S. Typhimurim to colonize the host tissues. During systemic infections, the single zupT mutant strain was attenuated only in Nramp1+/+ mice, but competition experiments between znuABC and znuABC zupT mutants revealed that ZupT contributes to metal uptake in vivo independently from the presence a functional Nramp1 transporter. Altogether, the here reported results show that ZupT plays an important role in Salmonella zinc homeostasis, being involved in metal import both in vitro and in infected animals. PMID:24430377

  6. The importance of heat evolution during the overcharge process and the protection mechanism of electrolyte additives for prismatic lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Shiun; Hu, Chi-Chang; Li, Yuan-Yao

    In this work, the rate of heat generation in the overcharge period for 103450 prismatic lithium ion batteries (LIBs) of the LiCoO 2-graphite jellyroll type with a basic electrolyte consisting of 1 M LiPF 6-PC/EC/EMC (1/3/5 in weight ratio) has been found to be more important than the gas evolution which was traditionally considered as the main reason in the overcharge protection mechanism. The cell voltage, charge current, and skin temperature were monitored during the charge process. For a single battery or batteries in parallel, LIBs without any additives is an acceptable design if the cell voltage is not charged above 4.55 V under the common charge program. The rate of heat generation from the polymerization of 3 wt% cyclohexyl benzene (CHB) is high enough to cause the explosion or thermal runaway of a battery, which is not found for an LIB containing 2 wt% CHB + 1 wt% tert-amyl benzene (TAB). In the 12 V overcharge test at 1C, the thermal fuse was broken by the high skin temperature (ca. 80 °C) due to the polymerization of 3 wt% CHB, which was also the case for LIBs containing 2 wt% CHB + 1 wt% TAB. The disconnection of the thermal fuse, however, did not interrupt the thermal runaway of LIBs without any additives because the battery voltage was too high (ca. 4.9 V). The influence of specific surface area of active materials in the anode on the polymerization kinetics of additives has to be carefully considered in order to add correct amount of overcharge protection agents.

  7. Physiological Roles and Adverse Effects of the Two Cystine Importers of Escherichia coli

    PubMed Central

    Chonoles Imlay, Karin R.; Korshunov, Sergey

    2015-01-01

    ABSTRACT When cystine is added to Escherichia coli, the bacterium becomes remarkably sensitive to hydrogen peroxide. This effect is due to enlarged intracellular pools of cysteine, which can drive Fenton chemistry. Genetic analysis linked the sensitivity to YdjN, a secondary transporter that along with the FliY-YecSC ABC system is responsible for cystine uptake. FliY-YecSC has a nanomolar Km and is essential for import of trace cystine, whereas YdjN has a micromolar Km and is the predominant importer when cystine is more abundant. Oddly, both systems are strongly induced by the CysB response to sulfur scarcity. The FliY-YecSC system can import a variety of biomolecules, including diaminopimelate; it is therefore vulnerable to competitive inhibition, presumably warranting YdjN induction under low-sulfur conditions. But the consequence is that if micromolar cystine then becomes available, the abundant YdjN massively overimports it, at >30 times the total sulfur demand of the cell. The imported cystine is rapidly reduced to cysteine in a glutathione-dependent process. This action avoids the hazard of disulfide stress, but it precludes feedback inhibition of YdjN by cystine. We conjecture that YdjN possesses no cysteine allosteric site because the isostructural amino acid serine might inappropriately bind in its place. Instead, the cell partially resolves the overaccumulation of cysteine by immediately excreting it, completing a futile import/reduction/export cycle that consumes a large amount of cellular energy. These unique, wasteful, and dangerous features of cystine metabolism are reproduced by other bacteria. We propose to rename ydjN as tcyP and fliY-yecSC as tcyJLN. IMPORTANCE In general, intracellular metabolite pools are kept at steady, nontoxic levels by a sophisticated combination of transcriptional and allosteric controls. Surprisingly, in E. coli allosteric control is utterly absent from the primary importer of cystine. This flaw allows massive overimport

  8. Teachers' Occupational Well-Being and Quality of Instruction: The Important Role of Self-Regulatory Patterns

    ERIC Educational Resources Information Center

    Klussman, Uta; Kunter, Mareike; Trautwein, Ulrich; Ludtke, Oliver; Baumert, Jurgen

    2008-01-01

    Teachers' occupational well-being (level of emotional exhaustion and job satisfaction) and quality of instruction are two key aspects of research on teaching that have rarely been studied together. The role of occupational engagement and resilience as two important work-related self-regulatory dimensions that predict occupational well-being and…

  9. What Is the Role and Importance of the Revised AERA, APA, NCME "Standards for Educational and Psychological Testing"?

    ERIC Educational Resources Information Center

    Plake, Barbara S.; Wise, Lauress L.

    2014-01-01

    With the 2014 publication of the 5th revision of the "Standards for Educational and Psychological Testing," the cochairs of the Joint Committee for the revision process were asked to consider the role and importance of the "Standards" for the educational testing community, and in particular for members of the National Council…

  10. State-of-the-Art Article: The Role and Importance of Lower-Level Processes in Second Language Reading

    ERIC Educational Resources Information Center

    Nassaji, Hossein

    2014-01-01

    This article examines current research on the role and importance of lower-level processes in second language (L2) reading. The focus is on word recognition and its subcomponent processes, including various phonological and orthographic processes. Issues related to syntactic and semantic processes and their relationship with word recognition are…

  11. Chemokines and their receptors play important roles in the development of hepatocellular carcinoma

    PubMed Central

    Liang, Chun-Min; Chen, Long; Hu, Heng; Ma, Hui-Ying; Gao, Ling-Ling; Qin, Jie; Zhong, Cui-Ping

    2015-01-01

    The chemokine system consists of four different subclasses with over 50 chemokines and 19 receptors. Their functions in the immune system have been well elucidated and research during the last decades unveils their new roles in hepatocellular carcinoma (HCC). The chemokines and their receptors in the microenvironment influence the development of HCC by several aspects including: inflammation, effects on immune cells, angiogenesis, and direct effects on HCC cells. Regarding these aspects, pre-clinical research by targeting the chemokine system has yielded promising data, and these findings bring us new clues in the chemokine-based therapies for HCC. PMID:26052384

  12. An Enquiry into the Role and Importance of Ethics in Scientific Research

    ERIC Educational Resources Information Center

    Massoudi, Mehrdad

    2008-01-01

    In this essay the importance of spirituality (or ethics) in the life of a research scientist is explored. The following four questions are considered: a) Why should the problem be studied? What are the benefits? and For whom? b) How should we approach this problem? c) What if the results of this investigation contradict other theories? What should…

  13. Atomic electron affinities and the role of symmetry between electron addition and subtraction in a corrected Koopmans approach.

    PubMed

    Teale, A M; De Proft, F; Geerlings, P; Tozer, D J

    2014-07-28

    The essential aspects of zero-temperature grand-canonical ensemble density-functional theory are reviewed in the context of spin-density-functional theory and are used to highlight the assumption of symmetry between electron addition and subtraction that underlies the corrected Koopmans approach of Tozer and De Proft (TDP) for computing electron affinities. The issue of symmetry is then investigated in a systematic study of atomic electron affinities, comparing TDP affinities with those from a conventional Koopmans evaluation and electronic energy differences. Although it cannot compete with affinities determined from energy differences, the TDP expression yields results that are a significant improvement over those from the conventional Koopmans expression. Key insight into the results from both expressions is provided by an analysis of plots of the electronic energy as a function of the number of electrons, which highlight the extent of symmetry between addition and subtraction. The accuracy of the TDP affinities is closely related to the nature of the orbitals involved in the electron addition and subtraction, being particularly poor in cases where there is a change in principal quantum number, but relatively accurate within a single manifold of orbitals. The analysis is then extended to a consideration of the ground state Mulliken electronegativity and chemical hardness. The findings further emphasize the key role of symmetry in determining the quality of the results. PMID:24406854

  14. Role of anaerobic fungi in wheat straw degradation and effects of plant feed additives on rumen fermentation parameters in vitro.

    PubMed

    Dagar, S S; Singh, N; Goel, N; Kumar, S; Puniya, A K

    2015-01-01

    In the present study, rumen microbial groups, i.e. total rumen microbes (TRM), total anaerobic fungi (TAF), avicel enriched bacteria (AEB) and neutral detergent fibre enriched bacteria (NEB) were evaluated for wheat straw (WS) degradability and different fermentation parameters in vitro. Highest WS degradation was shown for TRM, followed by TAF, NEB and least by AEB. Similar patterns were observed with total gas production and short chain fatty acid profiles. Overall, TAF emerged as the most potent individual microbial group. In order to enhance the fibrolytic and rumen fermentation potential of TAF, we evaluated 18 plant feed additives in vitro. Among these, six plant additives namely Albizia lebbeck, Alstonia scholaris, Bacopa monnieri, Lawsonia inermis, Psidium guajava and Terminalia arjuna considerably improved WS degradation by TAF. Further evaluation showed A. lebbeck as best feed additive. The study revealed that TAF plays a significant role in WS degradation and their fibrolytic activities can be improved by inclusion of A. lebbeck in fermentation medium. Further studies are warranted to elucidate its active constituents, effect on fungal population and in vivo potential in animal system. PMID:25391347

  15. Cd adsorption properties of components in different freshwater surface coatings: the important role of ferromanganese oxides.

    PubMed

    Dong, Deming; Hua, Xiuyi; Li, Yu; Zhang, Jingjing; Yan, Dongxu

    2003-09-15

    Surface coatings developed in different natural waters were used to study the role of the composition of surface coatings in controlling Cd adsorption in aquatic environments. To investigate the adsorption property of each component, the method of extraction techniques followed by Cd adsorption and statistical analysis were employed. Hydroxylamine hydrochloride was used to remove Mn oxides selectively, sodium dithionite was used to remove Mn and Fe oxides, and oxalic acid was used to remove most metal oxides and part of the organic material. Adsorption of Cd to surface coatings was measured before and after extraction under controlled laboratory conditions. The observed Cd adsorptions to unextracted and extracted surface coatings were analyzed using nonlinear least-squares fitting to estimate the adsorption property of each surface coating constituent. In different waters, the relative contribution to Cd adsorption of each component was different, but in all the waters studied, ferromanganese oxides contributed most with lesser roles indicated for organic phase and Al oxides. The Cd adsorption ability of manganese oxides was significantly higher than that of the other components. PMID:14524442

  16. The importance of microenvironment: the role of CCL8 in metastasis formation of melanoma.

    PubMed

    Barbai, Tamás; Fejős, Zsuzsanna; Puskas, Laszlo G; Tímár, József; Rásó, Erzsébet

    2015-10-01

    We have attempted to characterize the changes occurring on the host side during the progression of human melanoma. To investigate the role of tumor microenvironment, we set up such an animal model, which was able to isolate the host related factors playing central role in metastasis formation. One of these 'factors', CCL12, was consequently selected and its behavior was examined alongside its human homologue (CCL8). In our animal model, metastasis forming primary melanoma in the host exhibited increased level of CCL12 mRNA expression. In clinical samples, when examining the tumor and the host together, the cumulative (tumor and host) CCL8 expression was lower in the group in which human primary melanoma formed lung metastasis compared to non-metastatic primary tumors. We could not detect significant difference in CCL8 receptor (CCR1) expression between the two groups. Increased migration of the examined tumor cell lines was observed when CCL8 was applied as a chemoattractant. The tumor cells and their interactions can be influenced the expression of CCL8 by dermal fibroblasts, as a significant change in the metastatic microenvironment. Furthermore, we examined changes in miRNA profile resulted by CCL8 and miR146a appears to be a promising prognostic marker for following this process. PMID:26320180

  17. Polynucleotide phosphorylase plays an important role in the generation of spontaneous mutations in Escherichia coli.

    PubMed

    Becket, Elinne; Tse, Lawrence; Yung, Madeline; Cosico, Alexander; Miller, Jeffrey H

    2012-10-01

    Polynucleotide phosphorylase (PNP) plays a central role in RNA degradation, generating a pool of ribonucleoside diphosphates (rNDPs) that can be converted to deoxyribonucleoside diphosphates (dNDPs) by ribonucleotide reductase. We report here that spontaneous mutations resulting from replication errors, which are normally repaired by the mismatch repair (MMR) system, are sharply reduced in a PNP-deficient Escherichia coli strain. This is true for base substitution mutations that occur in the rpoB gene leading to Rif(r) and the gyrB gene leading to Nal(r) and for base substitution and frameshift mutations that occur in the lacZ gene. These results suggest that the increase in the rNDP pools generated by polynucleotide phosphorylase (PNP) degradation of RNA is responsible for the spontaneous mutations observed in an MMR-deficient background. The PNP-derived pool also appears responsible for the observed mutations in the mutT mutator background and those that occur after treatment with 5-bromodeoxyuridine, as these mutations are also drastically reduced in a PNP-deficient strain. However, mutation frequencies are not reduced in a mutY mutator background or after treatment with 2-aminopurine. These results highlight the central role in mutagenesis played by the rNDP pools (and the subsequent dNTP pools) derived from RNA degradation. PMID:22904280

  18. Polynucleotide Phosphorylase Plays an Important Role in the Generation of Spontaneous Mutations in Escherichia coli

    PubMed Central

    Becket, Elinne; Tse, Lawrence; Yung, Madeline; Cosico, Alexander

    2012-01-01

    Polynucleotide phosphorylase (PNP) plays a central role in RNA degradation, generating a pool of ribonucleoside diphosphates (rNDPs) that can be converted to deoxyribonucleoside diphosphates (dNDPs) by ribonucleotide reductase. We report here that spontaneous mutations resulting from replication errors, which are normally repaired by the mismatch repair (MMR) system, are sharply reduced in a PNP-deficient Escherichia coli strain. This is true for base substitution mutations that occur in the rpoB gene leading to Rifr and the gyrB gene leading to Nalr and for base substitution and frameshift mutations that occur in the lacZ gene. These results suggest that the increase in the rNDP pools generated by polynucleotide phosphorylase (PNP) degradation of RNA is responsible for the spontaneous mutations observed in an MMR-deficient background. The PNP-derived pool also appears responsible for the observed mutations in the mutT mutator background and those that occur after treatment with 5-bromodeoxyuridine, as these mutations are also drastically reduced in a PNP-deficient strain. However, mutation frequencies are not reduced in a mutY mutator background or after treatment with 2-aminopurine. These results highlight the central role in mutagenesis played by the rNDP pools (and the subsequent dNTP pools) derived from RNA degradation. PMID:22904280

  19. The importance of microenvironment: the role of CCL8 in metastasis formation of melanoma

    PubMed Central

    Barbai, Tamás; Fejős, Zsuzsanna; Puskas, Laszlo G.; Tímár, József; Rásó, Erzsébet

    2015-01-01

    We have attempted to characterize the changes occurring on the host side during the progression of human melanoma. To investigate the role of tumor microenvironment, we set up such an animal model, which was able to isolate the host related factors playing central role in metastasis formation. One of these ‘factors’, CCL12, was consequently selected and its behavior was examined alongside its human homologue (CCL8). In our animal model, metastasis forming primary melanoma in the host exhibited increased level of CCL12 mRNA expression. In clinical samples, when examining the tumor and the host together, the cumulative (tumor and host) CCL8 expression was lower in the group in which human primary melanoma formed lung metastasis compared to non-metastatic primary tumors. We could not detect significant difference in CCL8 receptor (CCR1) expression between the two groups. Increased migration of the examined tumor cell lines was observed when CCL8 was applied as a chemoattractant. The tumor cells and their interactions can be influenced the expression of CCL8 by dermal fibroblasts, as a significant change in the metastatic microenvironment. Furthermore, we examined changes in miRNA profile resulted by CCL8 and miR146a appears to be a promising prognostic marker for following this process. PMID:26320180

  20. [The role of the team of family physician in prevention of changing risk factors important in development of arterial hypertension].

    PubMed

    Beganlić, Azijada; Batić-Mujanović, Olivera; Tulumović, Ajsa; Zilzić, Muharem

    2005-01-01

    Arterial hypertension (AH) is one of the commonest noninfective chronic disease according to its important and the role in the morbidity and mortality, which is the reason for patients coming to the family phisician. Detection and treatment of high blood pressure are the major responsibility of physician in the primary care. If the family physician team (physician and nurse) make a good assessment of the risk factors which is important in development of arterial hypertension, the appearance of disease and its complications can be prevented or delayed. The most important for prevention of arterial hypertension is adoption a healthy lifestyle and it is nonseparate part of arterial hypertension treatment. PMID:16268072

  1. The novel zinc cluster regulator Tog1 plays important roles in oleate utilization and oxidative stress response in Saccharomyces cerevisiae

    SciTech Connect

    Thepnok, Piyasuda; Ratanakhanokchai, Khanok; Soontorngun, Nitnipa

    2014-08-08

    Highlights: • TOG1 deletion results in defective growth on non-fermentable carbon sources. • Removal of TOG1 sensitizes cells to oxidative stress. • Tog1 directly binds and activates expression of oleate utilizing genes. • The Δtog1 cells display reduced peroxisomal content in oleate culture. • S. cerevisiae zinc cluster Tog1 is a novel activator of oleate utilization. - Abstract: Many zinc cluster proteins have been shown to play a role in the transcriptional regulation of glucose-repressible genes during glucose exhaustion and diauxic shift. Here, we studied an additional member of this family called Yer184c (herein called Tog1) for transcriptional regulator of oleate. Our results showed that a Δtog1 strain displays impaired growth with several non-fermentable carbons. Tog1 is also implicated in oxidative stress tolerance. Importantly, during the glucose–oleate shift, combined results from quantitative real time-PCR and chromatin immunoprecipitation (ChIP) experiments showed that Tog1 acts as a direct activator of oleate utilizing genes, encoded key enzymes in β-Oxidation and NADPH regeneration (POX1, FOX2, POT1 and IDP2), the glyoxylate shunt (MLS1 and ICL1), and gluconeogenesis (PCK1 and FBP1). A transmission electron microscopy (TEM) analysis of the Δtog1 strain assayed with oleate also revealed a substantial decrease in peroxisome abundance that is vital for fatty acid oxidation. Overall, our results clearly demonstrated that Tog1 is a newly characterized zinc cluster regulator that functions in the complex network of non-fermentable carbon metabolism in Saccharomycescerevisiae.

  2. Abscisic Acid Plays an Important Role in the Regulation of Strawberry Fruit Ripening1[W][OA

    PubMed Central

    Jia, Hai-Feng; Chai, Ye-Mao; Li, Chun-Li; Lu, Dong; Luo, Jing-Jing; Qin, Ling; Shen, Yuan-Yue

    2011-01-01

    The plant hormone abscisic acid (ABA) has been suggested to play a role in fruit development, but supporting genetic evidence has been lacking. Here, we report that ABA promotes strawberry (Fragaria ananassa) fruit ripening. Using a newly established Tobacco rattle virus-induced gene silencing technique in strawberry fruit, the expression of a 9-cis-epoxycarotenoid dioxygenase gene (FaNCED1), which is key to ABA biosynthesis, was down-regulated, resulting in a significant decrease in ABA levels and uncolored fruits. Interestingly, a similar uncolored phenotype was observed in the transgenic RNA interference (RNAi) fruits, in which the expression of a putative ABA receptor gene encoding the magnesium chelatase H subunit (FaCHLH/ABAR) was down-regulated by virus-induced gene silencing. More importantly, the uncolored phenotype of the FaNCED1-down-regulated RNAi fruits could be rescued by exogenous ABA, but the ABA treatment could not reverse the uncolored phenotype of the FaCHLH/ABAR-down-regulated RNAi fruits. We observed that down-regulation of the FaCHLH/ABAR gene in the RNAi fruit altered both ABA levels and sugar content as well as a set of ABA- and/or sugar-responsive genes. Additionally, we showed that exogenous sugars, particularly sucrose, can significantly promote ripening while stimulating ABA accumulation. These data provide evidence that ABA is a signal molecule that promotes strawberry ripening and that the putative ABA receptor, FaCHLH/ABAR, is a positive regulator of ripening in response to ABA. PMID:21734113

  3. Fatty acid metabolism pathway play an important role in carcinogenesis of human colorectal cancers by Microarray-Bioinformatics analysis.

    PubMed

    Yeh, Ching-Sheng; Wang, Jaw-Yuan; Cheng, Tian-Lu; Juan, Chin-Hung; Wu, Chan-Han; Lin, Shiu-Ru

    2006-02-28

    The present study systematically explored metabolic pathways and altered expressions of genes speculatively participating in colorectal carcinogenesis by using a Microarray-Bioinformatic analysis methods. The results revealed that 157 genes were up-regulated and 281 genes were down-regulated in colorectal cancer (CRC). Gene Ontology (GO) and relevant bioinformatics tools indicated that the functional category to which 438 genes (12%; 438/3800) of the most frequent alteration belonged was metabolism. The analysis of 10 colorectal cancer tissue specimens demonstrated that genes involved in fatty acid metabolic pathways had high rates of overexpression. In addition, we stimulated CRL-1790 cell line with linoleic acid (a polyunsaturated fatty acid) for 12, 24, 48 and 72 h. Cell proliferation was elevated by 5, 25, 28 and 31% (P<0.05), respectively. Further analyses revealed that the genes increasingly expressed in the cell line included enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase (EHHADH), enoyl Coenzyme A hydratase, short chain, 1, mitochondrial (ECHS1); glutaryl-Coenzyme A dehydrogenase (GCDH), acyl-Coenzyme A oxidase 2, branched chain (ACOX2); acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain precursor (ACADS); carnitine palmitoyltransferase 1B (CPT1B), acyl-CoA synthetase long-chain family member 5 (ACSL5), and cytochrome P450, family 4, subfamily A, and polypeptide 11 (CYP4A11) genes. This indicated that the stimulating effect of linoleic acid on cell proliferation was due to interference with the metabolic pathway of fatty acid metabolism. In conclusion, genes with altered expression levels in CRC were mainly associated with fatty acid metabolic pathways speculated to have an important role linked to carcinogenesis. PMID:15885896

  4. Binding constraints on the evolution of enzymes and signalling proteins: the important role of negative pleiotropy.

    PubMed

    Liberles, David A; Tisdell, Makayla D M; Grahnen, Johan A

    2011-07-01

    A number of biophysical and population-genetic processes influence amino acid substitution rates. It is commonly recognized that proteins must fold into a native structure with preference over an unfolded state, and must bind to functional interacting partners favourably to function properly. What is less clear is how important folding and binding specificity are to amino acid substitution rates. A hypothesis of the importance of binding specificity in constraining sequence and functional evolution is presented. Examples include an evolutionary simulation of a population of SH2 sequences evolved by threading through the structure and binding to a native ligand, as well as SH3 domain signalling in yeast and selection for specificity in enzymatic reactions. An example in vampire bats where negative pleiotropy appears to have been adaptive is presented. Finally, considerations of compartmentalization and macromolecular crowding on negative pleiotropy are discussed. PMID:21490020

  5. Polymorphism in methylentetra-hydrofolate reductase gene: important role in diseases.

    PubMed

    Kiseljaković, Emina; Jadrić, Radivoj; Hasić, Sabaheta; Skenderi, Faruk; Resić, Halima; Winterhalter-Jadrić, Mira

    2008-05-01

    It has been recognized that some people have a genetic variant which leads to elevated levels of homocysteine and impairs ability to process folate. This condition was recognized as independent risk factor of coronary heart disease. Recently, connection between this termolabile mutation of the methylenetetrahydrofolate reductase and numerous conditions and diseases has been established. Aim of this review is to draw attention to this interesting area in medicine. Additionally, well defined study about presence and frequency of gene polymorphism in our region will provide proper diagnosis and achieve possible delay of development of diseases with vitamin supplementation. PMID:18498269

  6. Dysregulation of JAM-A plays an important role in human tumor progression

    PubMed Central

    Zhao, Chen; Lu, Funian; Chen, Hongxia; Zhao, Xianda; Sun, Jun; Chen, Honglei

    2014-01-01

    Junctional adhesion molecule A (JAM-A) is a transmembrane protein that belongs to the immunoglobulin (Ig) superfamily. Evidence determines that JAM-A plays a role in numerous cellular processes, including tight junction assembly, leukocyte migration, platelet activation, angiogenesis and virus binding. Recent research suggests that JAM-A is dysregulated in various cancers and is vital for tumor progression. JAM-A is implicated in carcinogenesis via different signal pathways such as TGF-β1 signaling. Furthermore, JAM-A expression in cancers is usually associated with certain outcome of patients and might be a prognostic indicator. In this review, the correlation between JAM-A expression and human cancers will be described. PMID:25400822

  7. Autophagy plays an important role in the containment of HIV-1 in nonprogressor-infected patients

    PubMed Central

    Nardacci, Roberta; Amendola, Alessandra; Ciccosanti, Fabiola; Corazzari, Marco; Esposito, Valentina; Vlassi, Chrysoula; Taibi, Chiara; Fimia, Gian Maria; Del Nonno, Franca; Ippolito, Giuseppe; D’Offizi, Gianpiero; Piacentini, Mauro

    2014-01-01

    Recent in vitro studies have suggested that autophagy may play a role in both HIV-1 replication and disease progression. In this study we investigated whether autophagy protects the small proportion of HIV-1 infected individuals who remain clinically stable for years in the absence of antiretroviral therapy, these named long-term nonprogressors (LTNP) and elite controllers (EC). We found that peripheral blood mononuclear cells (PBMC) of the HIV-1 controllers present a significantly higher amount of autophagic vesicles associated with an increased expression of autophagic markers with respect to normal progressors. Of note, ex vivo treatment of PBMC from the HIV-1 controllers with the MTOR inhibitor rapamycin results in a more efficient autophagic response, leading to a reduced viral production. These data lead us to propose that autophagy contributes to limiting viral pathogenesis in HIV-1 controllers by targeting viral components for degradation. PMID:24813622

  8. Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

    PubMed Central

    Metreau, J M; Yvart, J; Dhumeaux, D; Berthelot, P

    1978-01-01

    Gilbert's syndrome was diagnosed in 37 patients with unconjugated hyperbilirubinaemia without overt haemolysis or structural liver abnormality, who had a marked reduction in hepatic bilirubin UDP-glucuronosyltransferase activity (B-GTA) (as compared with that of 23 normal subjects). No significant correlation existed in these patients between serum bilirubin level and the values of B-GTA, thus suggesting that factors other than a low B-GTA must influence the degree of hyperbilirubinaemia in Gilbert's syndrome. Studies of 51Cr erythrocyte survival and 59Fe kinetics in 10 unselected patients demonstrated slight haemolysis in eight, whereas mild ineffective erythropoiesis was suggested in all from a low 24-hour incorporation of radioactive iron into circulating red cells. This overproduction of bilirubin resulting from mild haemolysis and perhaps dyserythropoiesis might reflect only an extreme degree of the normal situation. It certainly contributes to the hyperbilirubinaemia of Gilbert's syndrome and may play a major role in the manifestation of this condition. PMID:101425

  9. Important role of heparan sulfate in postnatal islet growth and insulin secretion

    SciTech Connect

    Takahashi, Iwao; Noguchi, Naoya; Nata, Koji; Yamada, Shuhei; Kaneiwa, Tomoyuki; Mizumoto, Shuji; Ikeda, Takayuki; Sugihara, Kazushi; Asano, Masahide; Yoshikawa, Takeo; Yamauchi, Akiyo; Shervani, Nausheen Jamal; Uruno, Akira; Kato, Ichiro; Unno, Michiaki; Sugahara, Kazuyuki; Takasawa, Shin; and others

    2009-05-22

    Heparan sulfate (HS) binds with several signaling molecules and regulates ligand-receptor interactions, playing an essential role in embryonic development. Here we showed that HS was intensively expressed in pancreatic islet {beta}-cells after 1 week of age in mice. The enzymatic removal of HS in isolated islets resulted in attenuated glucose-induced insulin secretion with a concomitant reduction in gene expression of several key components in the insulin secretion machinery. We further depleted islet HS by inactivating the exostosin tumor-like 3 gene specifically in {beta}-cells. These mice exhibited abnormal islet morphology with reduced {beta}-cell proliferation after 1 week of age and glucose intolerance due to defective insulin secretion. These results demonstrate that islet HS is involved in the regulation of postnatal islet maturation and required to ensure normal insulin secretion.

  10. Attenuated AMH signaling pathway plays an important role in the pathogenesis of ovarian hyperstimulation syndrome.

    PubMed

    Wang, Lan; Li, Hemei; Ai, Jihui; Yue, Jing; Li, Zhou; Zhang, Hanwang; Zhao, Yiqing

    2015-01-01

    The aim of this study is to investigate the potential role of attenuated anti-Müllerian hormone signaling in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). To analyze the expression of AMH and its receptors in human follicular fluid (FF) and granulosa cells (GCs), this study included consenting patients with moderate to severe OHSS (n = 83) and non-OHSS patients (control population, n = 108) undergoing IVF/ICSI treatment between March 2013 and March 2014. AMH concentrations in single FF samples from the OHSS patients were significantly lower than concentrations in samples from the control group. A negative correlation was found between the E2 level and the AMH level in single FF samples. Similarly, a negative correlation was found between the FF AMH level and the number of oocytes retrieved. Although the mRNA expression level of AMH was hardly detectable in GCs, the mRNA expression level of AMHR2 in GCs from OHSS patients was significantly lower than the AMHR2 mRNA expression level in the control population. Based on these results, we established a murine model of controlled ovarian hyperstimulation (COH) using AMHR2-down-regulated mice to demonstrate the potential role of AMH signaling in the progression of OHSS. The knockdown of AMHR2 is capable of significantly increasing the ovarian response to exogenous gonadotropins, leading to several major clinical manifestations of OHSS in the murine model. In conclusion, attenuated AMH signaling increases ovarian sensitivity to COH and the incidence of OHSS in individuals undergoes IVF/ICSI. PMID:26692936

  11. Secretory leukocyte protease inhibitor plays an important role in the regulation of allergic asthma in mice.

    PubMed

    Marino, Rafael; Thuraisingam, Thusanth; Camateros, Pierre; Kanagaratham, Cynthia; Xu, Yong Zhong; Henri, Jennifer; Yang, Jingxuan; He, Guoan; Ding, Aihao; Radzioch, Danuta

    2011-04-01

    Secretory leukocyte protease inhibitor (SLPI) is an anti-inflammatory protein that is observed at high levels in asthma patients. Resiquimod, a TLR7/8 ligand, is protective against acute and chronic asthma, and it increases SLPI expression of macrophages in vitro. However, the protective role played by SLPI and the interactions between the SLPI and resiquimod pathways in the immune response occurring in allergic asthma have not been fully elucidated. To evaluate the role of SLPI in the development of asthma phenotypes and the effect of resiquimod treatment on SLPI, we assessed airway resistance and inflammatory parameters in the lungs of OVA-induced asthmatic SLPI transgenic and knockout mice and in mice treated with resiquimod. Compared with wild-type mice, allergic SLPI transgenic mice showed a decrease in lung resistance (p < 0.001), airway eosinophilia (p < 0.001), goblet cell hyperplasia (p < 0.001), and plasma IgE levels (p < 0.001). Allergic SLPI knockout mice displayed phenotype changes significantly more severe compared with wild-type mice. These phenotypes included lung resistance (p < 0.001), airway eosinophilia (p < 0.001), goblet cell hyperplasia (p < 0.001), cytokine levels in the lungs (p < 0.05), and plasma IgE levels (p < 0.001). Treatment of asthmatic transgenic mice with resiquimod increased the expression of SLPI and decreased inflammation in the lungs; resiquimod treatment was still effective in asthmatic SLPI knockout mice. Taken together, our study showed that the expression of SLPI protects against allergic asthma phenotypes, and treatment by resiquimod is independent of SLPI expression, displayed through the use of transgenic and knockout SLPI mice. PMID:21335488

  12. Attenuated AMH signaling pathway plays an important role in the pathogenesis of ovarian hyperstimulation syndrome

    PubMed Central

    Wang, Lan; Li, Hemei; Ai, Jihui; Yue, Jing; Li, Zhou; Zhang, Hanwang; Zhao, Yiqing

    2015-01-01

    The aim of this study is to investigate the potential role of attenuated anti-Müllerian hormone signaling in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). To analyze the expression of AMH and its receptors in human follicular fluid (FF) and granulosa cells (GCs), this study included consenting patients with moderate to severe OHSS (n = 83) and non-OHSS patients (control population, n = 108) undergoing IVF/ICSI treatment between March 2013 and March 2014. AMH concentrations in single FF samples from the OHSS patients were significantly lower than concentrations in samples from the control group. A negative correlation was found between the E2 level and the AMH level in single FF samples. Similarly, a negative correlation was found between the FF AMH level and the number of oocytes retrieved. Although the mRNA expression level of AMH was hardly detectable in GCs, the mRNA expression level of AMHR2 in GCs from OHSS patients was significantly lower than the AMHR2 mRNA expression level in the control population. Based on these results, we established a murine model of controlled ovarian hyperstimulation (COH) using AMHR2-down-regulated mice to demonstrate the potential role of AMH signaling in the progression of OHSS. The knockdown of AMHR2 is capable of significantly increasing the ovarian response to exogenous gonadotropins, leading to several major clinical manifestations of OHSS in the murine model. In conclusion, attenuated AMH signaling increases ovarian sensitivity to COH and the incidence of OHSS in individuals undergoes IVF/ICSI. PMID:26692936

  13. Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila

    PubMed Central

    Sitnik, Jessica L.; Francis, Carmen; Hens, Korneel; Huybrechts, Roger; Wolfner, Mariana F.; Callaerts, Patrick

    2014-01-01

    Members of the M13 class of metalloproteases have been implicated in diseases and in reproductive fitness. Nevertheless, their physiological role remains poorly understood. To obtain a tractable model with which to analyze this protein family’s function, we characterized the gene family in Drosophila melanogaster and focused on reproductive phenotypes. The D. melanogaster genome contains 24 M13 class protease homologs, some of which are orthologs of human proteases, including neprilysin. Many are expressed in the reproductive tracts of either sex. Using RNAi we individually targeted the five Nep genes most closely related to vertebrate neprilysin, Nep1-5, to investigate their roles in reproduction. A reduction in Nep1, Nep2, or Nep4 expression in females reduced egg laying. Nep1 and Nep2 are required in the CNS and the spermathecae for wild-type fecundity. Females that are null for Nep2 also show defects as hosts of sperm competition as well as an increased rate of depletion for stored sperm. Furthermore, eggs laid by Nep2 mutant females are fertilized normally, but arrest early in embryonic development. In the male, only Nep1 was required to induce normal patterns of female egg laying. Reduction in the expression of Nep2-5 in the male did not cause any dramatic effects on reproductive fitness, which suggests that these genes are either nonessential for male fertility or perform redundant functions. Our results suggest that, consistent with the functions of neprilysins in mammals, these proteins are also required for reproduction in Drosophila, opening up this model system for further functional analysis of this protein class and their substrates. PMID:24395329

  14. TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes.

    PubMed

    Oosting, Marije; Ter Hofstede, Hadewych; Sturm, Patrick; Adema, Gosse J; Kullberg, Bart-Jan; van der Meer, Jos W M; Netea, Mihai G; Joosten, Leo A B

    2011-01-01

    After infection with Borrelia species, the risk for developing Lyme disease varies significantly between individuals. Recognition of Borrelia by the immune system is mediated by pattern recognition receptors (PRRs), such as TLRs. While TLR2 is the main recognition receptor for Borrelia spp., little is known about the role of TLR1 and TLR6, which both can form functionally active heterodimers with TLR2. Here we investigated the recognition of Borrelia by both murine and human TLR1 and TLR6. Peritoneal macrophages from TLR1- and TLR6- gene deficient mice were isolated and exposed to Borrelia. Human PBMCs were stimulated with Borrelia with or without specific TLR1 and TLR6 blocking using specific antibodies. Finally, the functional consequences of TLR polymorphisms on Borrelia-induced cytokine production were assessed. Splenocytes isolated from both TLR1-/- and TLR6-/- mice displayed a distorted Th1/Th2 cytokine balance after stimulation with B.burgdorferi, while no differences in pro-inflammatory cytokine production were observed. In contrast, blockade of TLR1 with specific neutralizing antibodies led to decreased cytokine production by human PBMCs after exposure to B.burgdorferi. Blockade of human TLR6 did not lead to suppression of cytokine production. When PBMCs from healthy individuals bearing polymorphisms in TLR1 were exposed to B.burgdorferi, a remarkably decreased in vitro cytokine production was observed in comparison to wild-type controls. TLR6 polymorphisms lead to a minor modified cytokine production. This study indicates a dominant role for TLR1/TLR2 heterodimers in the induction of the early inflammatory response by Borrelia spirochetes in humans. PMID:21998742

  15. Peptidoglycan Crosslinking Relaxation Plays an Important Role in Staphylococcus aureus WalKR-Dependent Cell Viability

    PubMed Central

    Delaune, Aurelia; Poupel, Olivier; Mallet, Adeline; Coic, Yves-Marie; Msadek, Tarek; Dubrac, Sarah

    2011-01-01

    The WalKR two-component system is essential for viability of Staphylococcus aureus, a major pathogen. We have shown that WalKR acts as the master controller of peptidoglycan metabolism, yet none of the identified regulon genes explain its requirement for cell viability. Transmission electron micrographs revealed cell wall thickening and aberrant division septa in the absence of WalKR, suggesting its requirement may be linked to its role in coordinating cell wall metabolism and cell division. We therefore tested whether uncoupling autolysin gene expression from WalKR-dependent regulation could compensate for its essential nature. Uncoupled expression of genes encoding lytic transglycosylases or amidases did not restore growth to a WalKR-depleted strain. We identified only two WalKR-regulon genes whose expression restored cell viability in the absence of WalKR: lytM and ssaA. Neither of these two genes are essential under our conditions and a ΔlytM ΔssaA mutant does not present any growth defect. LytM is a glycyl–glycyl endopeptidase, hydrolyzing the pentaglycine interpeptide crossbridge, and SsaA belongs to the CHAP amidase family, members of which such as LysK and LytA have been shown to have D-alanyl-glycyl endopeptidase activity, cleaving between the crossbridge and the stem peptide. Taken together, our results strongly suggest that peptidoglycan crosslinking relaxation through crossbridge hydrolysis plays a crucial role in the essential requirement of the WalKR system for cell viability. PMID:21386961

  16. Conserved Ser/Arg-rich Motif in PPZ Orthologs from Fungi Is Important for Its Role in Cation Tolerance

    PubMed Central

    Minhas, Anupriya; Sharma, Anupam; Kaur, Harsimran; Rawal, Yashpal; Ganesan, Kaliannan; Mondal, Alok K.

    2012-01-01

    PPZ1 orthologs, novel members of a phosphoprotein phosphatase family of phosphatases, are found only in fungi. They regulate diverse physiological processes in fungi e.g. ion homeostasis, cell size, cell integrity, etc. Although they are an important determinant of salt tolerance in fungi, their physiological role remained unexplored in any halotolerant species. In this context we report here molecular and functional characterization of DhPPZ1 from Debaryomyces hansenii, which is one of the most halotolerant and osmotolerant species of yeast. Our results showed that DhPPZ1 knock-out strain displayed higher tolerance to toxic cations, and unlike in Saccharomyces cerevisiae, Na+/H+ antiporter appeared to have an important role in this process. Besides salt tolerance, DhPPZ1 also had role in cell wall integrity and growth in D. hansenii. We have also identified a short, serine-arginine-rich sequence motif in DhPpz1p that is essential for its role in salt tolerance but not in other physiological processes. Taken together, these results underscore a distinct role of DhPpz1p in D. hansenii and illustrate an example of how organisms utilize the same molecular tool box differently to garner adaptive fitness for their respective ecological niches. PMID:22232558

  17. Pectin plays an important role on the kinetics properties of polyphenol oxidase from honeydew peach.

    PubMed

    Liu, Liang; Cao, Shaoqian; Yang, Hua; Qi, Xiangyang

    2015-02-01

    Polyphenol oxidase (PPO) was purified from peach pulp by a three-step column chromatographic procedure. The kinetics properties of the PPO fractions obtained from different purification steps were compared. All the fractions showed high affinities for (+)-catechin and (-)-epicatechin. The optimum pHs and optimum temperatures for all the fractions were the same. However, the fraction that contained pectin was more sensitive to the change of pH, and it had a lower affinity for the substrates and a higher thermostability than the fractions without pectin. In addition, the protein impurities in PPO fractions might have no effect on the properties of PPO. l-Cysteine and glutathione were effective for the inhibition of all the PPO fractions, while NaF inhibited moderately. However, the pectin could reduce the inhibition effects of those inhibitors. PMID:25172677

  18. Natural organic matter as electron acceptor: experimental evidence for its important role in anaerobic respiration

    NASA Astrophysics Data System (ADS)

    Lau, Maximilian Peter; Sander, Michael; Gelbrecht, Jörg; Hupfer, Michael

    2014-05-01

    Microbial respiration is a key driver of element cycling in oxic and anoxic environments. Upon depletion of oxygen as terminal electron acceptor (TEA), a number of anaerobic bacteria can employ alternative TEA for intracellular energy generation. Redox active quinone moieties in dissolved organic matter (DOM) are well known electron acceptors for microbial respiration. However, it remains unclear whether quinones in adsorbed and particulate OM accept electrons in a same way. In our studies we aim to understand the importance of natural organic matter (NOM) as electron acceptors for microbial energy gain and its possible implications for methanogenesis. Using a novel electrochemical approach, mediated electrochemical reduction and -oxidation, we can directly quantify reduced hydroquinone and oxidized quionone moieties in dissolved and particulate NOM samples. In a mesocosm experiment, we rewetted sediment and peat soil and followed electron transfer to the inorganic and organic electron acceptors over time. We found that inorganic and organic electron acceptor pools were depleted over the same timescales. More importantly, we showed that organic, NOM-associated electron accepting moieties represent as much as 21 40% of total TEA inventories. These findings support earlier studies that propose that the reduction of quinone moieties in particulate organic matter competitively suppresses methanogenesis in wetland soils. Our results indicate that electron transfer to organic, particulate TEA in inundated ecosystems has to be accounted for when establishing carbon budgets in and projecting greenhouse gas emissions from these systems.

  19. The role and importance of gene polymorphisms in the development of atherosclerosis.

    PubMed

    Szabó, Gábor Viktor

    2013-03-01

    The development of atherosclerosis is a multifactorial process. The purpose of the study was to examine three genetic polymorphisms playing a role in the metabolic processes underlying the disease. We compared the data of 348 atherosclerotic non-diabetic patients with 260 atherosclerotic diabetic patients and 384 healthy controls. We analyzed the prevalence of myocardial infarction and stroke in three different groups of patients carrying different polymorphisms. It was proved that if the mutant TT eNOS Glu298ASP variant is present, a significantly higher number of myocardial infarctions can be observed than in patients carrying heterozygote GT or normal GG genotype. We proved that in the case of MTHFR 677CT heterozygote variants, the occurrence of myocardial infarction is significantly higher and the difference is also significant in case of the 677TT homozygote variant. It was verified that among patients with the mutant TNF-α AA genotype the occurrence of cardiovascular events was significantly higher. Screening the genetically high risk groups on the long run should be considered as an early detection opportunity that may give better chances for prevention and treatment. Understanding the inflammatory mechanisms of the atherosclerosis may give new therapeutical targets to pharmacologists. PMID:24265890

  20. Did large animals play an important role in global biogeochemical cycling in the past?

    NASA Astrophysics Data System (ADS)

    Doughty, C.

    2014-12-01

    In the late Pleistocene (~50-10,000 years ago), ninety-seven genera of large animals (>44kg) (megafauna) went extinct, concentrated in the Americas and Australia. The loss of megafauna had major effects on ecosystem structure, seed dispersal and land surface albedo. However, the impact of this dramatic extinction on ecosystem nutrient biogeochemistry, through the lateral transport of dung and bodies, has never been explored. Here we explore these nutrient impacts using a novel mathematical framework that analyses this lateral transport as a diffusion-like process and demonstrates that large animals play a disproportionately large role in the horizontal transfer of nutrients across landscapes. For example, we estimate that the extinction of the Amazonian megafauna led to a >98% reduction in the lateral transfer flux of the limiting nutrient phosphorus (P) with similar, though less extreme, decreases in all continents outside of Africa. This resulted in strong decreases in phosphorus availability in Eastern Amazonia away from fertile floodplains, a decline which may still be ongoing, and current P limitation in the Amazon basin may be partially a relic of an ecosystem without the functional connectedness it once had. More broadly, the Pleistocene megafaunal extinctions resulted in major and ongoing disruptions to terrestrial biogeochemical cycling at continental scales and increased nutrient heterogeneity globally.

  1. Aquaporin-1 plays important role in proliferation by affecting cell cycle progression.

    PubMed

    Galán-Cobo, Ana; Ramírez-Lorca, Reposo; Toledo-Aral, Juan José; Echevarría, Miriam

    2016-01-01

    Aquaporin-1 (AQP1) has been associated with tumor development. Here, we investigated how AQP1 may affect cell proliferation. The proliferative rate of adult carotid body (CB) cells, known to proliferate under chronic hypoxia, was analyzed in wild-type (AQP1(+/+) ) and knock out (AQP1(-/-) ) mice, maintained in normoxia or exposed to hypoxia while BrdU was administered. Fewer numbers of total BrdU(+) and TH-BrdU(+) cells were observed in AQP1(-/-) mice, indicating a role for AQP1 in CB proliferation. Then, by flow cytometry, cell cycle state and proliferation of cells overexpressing AQP1 were compared to those of wild-type cells. In the AQP1-overexpressing cells, we observed higher cell proliferation and percentages of cells in phases S and G2/M and fewer apoptotic cells after nocodazole treatment were detected by annexin V staining. Also in these cells, proteomic assays showed higher expression of cyclin D1 and E1 and microarray analysis revealed changes in many cell proliferation-related molecules, including, Zeb 2, Jun, NF-kβ, Cxcl9, Cxcl10, TNF, and the TNF receptor. Overall, our results indicate that the presence of AQP1 modifies the expression of key cell cycle proteins apparently related to increases in cell proliferation. This contributes to explaining the presence of AQP1 in many different tumors. PMID:26081645

  2. Inflammasome activation has an important role in the development of spontaneous colitis.

    PubMed

    Zhang, J; Fu, S; Sun, S; Li, Z; Guo, B

    2014-09-01

    Inflammatory bowel disease (IBD) is characterized for dysregulated intestinal inflammation. Conflicting reports have shown that activation of inflammasome could promote or decrease intestinal inflammation in an acute colitis model, whereas the involvement of inflammasome activation in chronic colitis is poorly understood. In this study, we investigated the role of inflammasome activation in the development of chronic intestinal inflammation by utilizing interleukin-10 (IL-10) knockout (KO) mouse as an animal model, which develops chronic colitis resembling human IBD. We demonstrate the causative link between inflammasome activation and the development of chronic intestinal inflammation. Our results show that mature IL-1β protein levels were significantly increased in all colon sections from IL-10-deficient mice compared with that of wild-type mice. We found that inhibition of inflammasome activities with IL-1 receptor antagonist or caspase-1 inhibitors suppressed IL-1β and IL-17 production from inflamed colon explants. Furthermore, blocking inflammasome activation with caspase-1 inhibitor in vivo significantly ameliorated the spontaneous colitis in IL-10 KO mice. Taken together, these observations demonstrate that inflammasome activation promotes the development of chronic intestinal inflammation. PMID:24472848

  3. Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis.

    PubMed

    Shiraishi, J; Tatsumi, T; Keira, N; Akashi, K; Mano, A; Yamanaka, S; Matoba, S; Asayama, J; Yaoi, T; Fushiki, S; Fliss, H; Nakagawa, M

    2001-10-01

    Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation. PMID:11557554

  4. The role and importance of porosity in the deflagration rates of HMX-based materials

    SciTech Connect

    Glascoe, E A; Hsu, P C; Springer, H K

    2011-03-15

    The deflagration behavior of thermally damaged HMX-based materials will be discussed. Strands of material were burned at pressures ranging from 10-300 MPa using the LLNL high pressure strand burner. Strands were heated in-situ and burned while still hot; temperatures range from 90-200 C and were chosen in order to allow for thermal damage of the material without significant decomposition of the HMX. The results indicate that multiple variables affect the burn rate but the most important are the polymorph of HMX and the nature and thermal stability of the non-HE portion of the material. Characterization of the strands indicate that the thermal soak produces significant porosity and permeability in the sample allowing for significantly faster burning due to the increased surface area and new pathways for flame spread into the material. Specifically, the deflagration rates of heated PBXN-9, LX-10, and PBX-9501 will be discussed and compared.

  5. Role of extracellular polymeric substances in enhancement of phosphorus release from waste activated sludge by rhamnolipid addition.

    PubMed

    He, Zhang-Wei; Liu, Wen-Zong; Wang, Ling; Yang, Chun-Xue; Guo, Ze-Chong; Zhou, Ai-Juan; Liu, Jian-Yong; Wang, Ai-Jie

    2016-02-01

    This study investigated the role of extracellular polymeric substances (EPSs) in enhanced performance of phosphorus (P) release from waste activated sludge (WAS) by adding rhamnolipid (RL). Results showed that compared to WAS without pretreatment, the released PO4(3-)-P increased with RL addition from 0 to 0.2 g/gTSS (total suspended solid), and increased by 208% under the optimal condition (0.1 g RL/g TSS and 72-h fermentation time). The cumulative PO4(3-)-P was better fitted with pseudo-first-order kinetic model. Moreover, the contents of metal ions increased in liquid but decreased in EPSs linearly with RL addition increasing, and WAS solubilizations were positively correlated with the released metal ions. The enhanced total dissolved P mainly came from cells and others (69.39%, 2.27-fold higher than that from EPSs), and PO4(3-)-P was the main species in both liquid and loosely bound EPSs, but organic P should be non-negligible in tightly bound EPSs. PMID:26700759

  6. Excitons in van der Waals heterostructures: The important role of dielectric screening

    NASA Astrophysics Data System (ADS)

    Latini, S.; Olsen, T.; Thygesen, K. S.

    2015-12-01

    The existence of strongly bound excitons is one of the hallmarks of the newly discovered atomically thin semiconductors. While it is understood that the large binding energy is mainly due to the weak dielectric screening in two dimensions, a systematic investigation of the role of screening on two-dimensional (2D) excitons is still lacking. Here we provide a critical assessment of a widely used 2D hydrogenic exciton model, which assumes a dielectric function of the form ɛ (q )=1 +2 π α q , and we develop a quasi-2D model with a much broader applicability. Within the quasi-2D picture, electrons and holes are described as in-plane point charges with a finite extension in the perpendicular direction, and their interaction is screened by a dielectric function with a nonlinear q dependence which is computed ab initio. The screened interaction is used in a generalized Mott-Wannier model to calculate exciton binding energies in both isolated and supported 2D materials. For isolated 2D materials, the quasi-2D treatment yields results almost identical to those of the strict 2D model, and both are in good agreement with ab initio many-body calculations. On the other hand, for more complex structures such as supported layers or layers embedded in a van der Waals heterostructure, the size of the exciton in reciprocal space extends well beyond the linear regime of the dielectric function, and a quasi-2D description has to replace the 2D one. Our methodology has the merit of providing a seamless connection between the strict 2D limit of isolated monolayer materials and the more bulk-like screening characteristics of supported 2D materials or van der Waals heterostructures.

  7. Important Role of Platelets in Modulating Endotoxin-Induced Lung Inflammation in CFTR-Deficient Mice

    PubMed Central

    Zhao, Caiqi; Su, Emily M.; Yang, Xi; Gao, Zhaowei; Li, Ling; Wu, Haiya; Jiang, Yiyi; Su, Xiao

    2013-01-01

    Abstract Mutation of CFTR (cystic fibrosis transmembrane conductance regulator) leads to cystic fibrosis (CF). Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation) mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels). Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1), platelet activating factor (PAF), and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF), or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients. PMID:24367540

  8. On the performance of low pressure die-cast Al-Cu based automotive alloys: Role of additives

    NASA Astrophysics Data System (ADS)

    Zaki, Gergis Adel

    The present study focuses on the effect of alloying elements, namely, strontium (Sr), titanium (Ti), zirconium (Zr), scandium (Sc) and silver(Ag) individually or in combination, on the performance of a newly developed Al-2%Cu based alloy. A total of thirteen alloy compositions were used in the study. Tensile test bar castings were prepared employing the low pressure die casting (LPDC) technique. The test bars were solution heat treated at 495°C for 8 hours, followed by quenching in warm water, and then subjected to different isochronal aging treatments using an aging time of 5 hours and aging temperatures of 155°C, 180°C, 200°C, 240°C and 300°C. Tensile testing of as-cast and heat-treated test bars was carried out at room temperature using a strain rate of 4 x 10-4s-1. Five test bars were used per alloy composition/condition. Hardness measurements were also carried out on these alloys using a Brinell hardness tester. The microstructures of selected samples were examined using optical microscopy and electron probe microanalysis (EPMA). The results showed that adding Ti in the amount of 0.15 wt% in the form of Al-5%Ti-1%B master alloy is sufficient to refine the grains in the cast structure in the presence of 200 ppm Sr (0.02 wt%). Addition of Zr and Sc did not contribute further to the grain refining effect. The main role of addition of these two elements appeared in the formation of complex compounds with Al and Ti. Their presence resulted in extending the aging temperature range before the onset of softening. Mathematical analysis of the hardness and tensile data was carried out using the Minitab statistical software program. It was determined that the alloy containing (0.5wt% Zr + 0.15wt% Ti) is the most effective in maximizing the alloy tensile strength over the range of aging temperatures, from 155°C to 300°C. Addition of Ag is beneficial at high aging temperatures, in the range of 240°C-300°C. However, it is less effective compared to the (Zr + Ti

  9. Humidity plays an important role in the PM₂.₅ pollution in Beijing.

    PubMed

    Cheng, Yuan; He, Ke-bin; Du, Zhen-yu; Zheng, Mei; Duan, Feng-kui; Ma, Yong-liang

    2015-02-01

    Heavily-polluted PM₂.₅ (fine particulate matter) episodes frequently impacting Beijing, especially during winter, have become a substantial concern. We found that during winter, the daily variation of PM2.5 in Beijing tracked the pattern of relative humidity (RH). With the increase of PM₂.₅ (or RH), water-soluble components (especially inorganic ions) became more abundant, and the water-soluble organic carbon to organic carbon ratios increased. The nitrate to sulfate ratios also exhibited dependence on RH, and were higher than those measured about a decade ago, consistent with the increasing trend of nitrogen oxides emissions. Surprisingly, the ratios of water-insoluble organic carbon to elemental carbon showed significant increase at high RH levels, presumably indicating the formation of secondary organic aerosol that is not soluble in water. In addition, humid winters were occasionally identified during 1996-2013 which are expected to be favorable for the formation of air pollution episodes with high PM₂.₅ concentrations. PMID:25497308

  10. Ribosome profiling reveals an important role for translational control in circadian gene expression

    PubMed Central

    Jang, Christopher; Lahens, Nicholas F.; Hogenesch, John B.; Sehgal, Amita

    2015-01-01

    Physiological and behavioral circadian rhythms are driven by a conserved transcriptional/translational negative feedback loop in mammals. Although most core clock factors are transcription factors, post-transcriptional control introduces delays that are critical for circadian oscillations. Little work has been done on circadian regulation of translation, so to address this deficit we conducted ribosome profiling experiments in a human cell model for an autonomous clock. We found that most rhythmic gene expression occurs with little delay between transcription and translation, suggesting that the lag in the accumulation of some clock proteins relative to their mRNAs does not arise from regulated translation. Nevertheless, we found that translation occurs in a circadian fashion for many genes, sometimes imposing an additional level of control on rhythmically expressed mRNAs and, in other cases, conferring rhythms on noncycling mRNAs. Most cyclically transcribed RNAs are translated at one of two major times in a 24-h day, while rhythmic translation of most noncyclic RNAs is phased to a single time of day. Unexpectedly, we found that the clock also regulates the formation of cytoplasmic processing (P) bodies, which control the fate of mRNAs, suggesting circadian coordination of mRNA metabolism and translation. PMID:26338483

  11. DNA Double-Strand Breaks and Telomeres Play Important Roles in Trypanosoma brucei Antigenic Variation

    PubMed Central

    2015-01-01

    Human-infecting microbial pathogens all face a serious problem of elimination by the host immune response. Antigenic variation is an effective immune evasion mechanism where the pathogen regularly switches its major surface antigen. In many cases, the major surface antigen is encoded by genes from the same gene family, and its expression is strictly monoallelic. Among pathogens that undergo antigenic variation, Trypanosoma brucei (a kinetoplastid), which causes human African trypanosomiasis, Plasmodium falciparum (an apicomplexan), which causes malaria, Pneumocystis jirovecii (a fungus), which causes pneumonia, and Borrelia burgdorferi (a bacterium), which causes Lyme disease, also express their major surface antigens from loci next to the telomere. Except for Plasmodium, DNA recombination-mediated gene conversion is a major pathway for surface antigen switching in these pathogens. In the last decade, more sophisticated molecular and genetic tools have been developed in T. brucei, and our knowledge of functions of DNA recombination in antigenic variation has been greatly advanced. VSG is the major surface antigen in T. brucei. In subtelomeric VSG expression sites (ESs), VSG genes invariably are flanked by a long stretch of upstream 70-bp repeats. Recent studies have shown that DNA double-strand breaks (DSBs), particularly those in 70-bp repeats in the active ES, are a natural potent trigger for antigenic variation in T. brucei. In addition, telomere proteins can influence VSG switching by reducing the DSB amount at subtelomeric regions. These findings will be summarized and their implications will be discussed in this review. PMID:25576484

  12. An important role of carotenoids in protection of photosynthetic apparatus under VAM inoculation on Momordica charantia.

    PubMed

    Azmat, Rafia

    2013-01-01

    The effect of mixed inoculums of VAM (Vesicular Arbuscular Mycorrhizas) fungi on seed growth and photosynthetic apparatus in green house was monitored. The plants were watered daily with tap water. Plants were cultivated in natural environment in mid of March (2011). A direct relation between root length and water contents suggests a defense mechanism of MP (microrihzal plants) against the fungal stress. It was also supported by the fact that the leaf area of MP was much greater as compared to the NMP (non microrihzal plants) with elevated concentration of all chlorophyllus pigments in 30 days. An increase in the surface area of the leaf and concentration of the pigments, may be for an acceleration in absorption of CO₂ for reduction of it into glucose through oxidation of water molecule. The non-significant decline in glucose contents support the above hypothesis of rapid redox reaction mechanism which was established to overcome the stress. The positive effects of mycorrhizal which were already mentioned in the literature were reported in this article in relations of survival strategies of the plant, adapted in stress conditions. An increase in the chlorophyll contents (30 d) and leaf area of plants possibly attributed with absorption of solar radiation for the protection of plants. It was also supported by the higher concentration of carotenoids (30 d) that may have an additional function of regulation of certain developmental responses and screening of light to save the plants from stress conditions. PMID:24372263

  13. Role of UV light in photodamage, skin aging, and skin cancer: importance of photoprotection.

    PubMed

    Gonzaga, Evelyn R

    2009-01-01

    Solar, and particularly UV, radiation causes molecular and cellular damage with resultant histopathologic and clinical degenerative changes, leading in turn to photosensitivity, photo-aging, and skin cancer. While our bodies have some natural UV defenses, additional protection from the sun is essential, including sun avoidance, physical protection, and sunscreen use. Sun avoidance includes limiting exposure during peak UV times (10am-4pm), avoiding UV-reflective surfaces such as sand, snow and water, and eliminating photosensitizing drugs. Physical protection includes wearing photoprotective clothing such as a broad-brimmed hat and long sleeves and use of UV-blocking films on windows. Sunscreen containing avobenzone, titanium dioxide, zinc oxide or encamsule should be used daily and frequently reapplied. To guard against the UVB spectrum, zinc oxide and titanium dioxide are particularly recommended. Sunscreen is generally under-applied at only 25% of the recommended dose, seriously compromising photoprotection. Dosage guidelines recommend using more than half a teaspoon each on head and neck area and each arm, and more than a teaspoon each on anterior torso, posterior torso, and each leg (approximately 2 mg/cm(2)). PMID:19209950

  14. [The important role of vitamins in the over-production of pyruvic acid].

    PubMed

    Li, Y; Chen, J; Lun, S; Rui, X

    2000-10-01

    The effect of nicotinic acid, thiamine, pyridoxine, biotin and riboflavin on the production of pyruvic acid by Torulopsis glabrata WSH-IP303 with glucose as carbon source and NH4Cl as sole nitrogen source was investigated. By using orthogonal experiment method, thiamine was confirmed to be the most important factor affecting the production of pyruvic acid. Based on a certain concentration range of thiamine (0.01-0.015 mg/L), glucose consumption rate can be enhanced by increasing the concentration of nicotinic acid. When the concentration of nicotinic acid, thiamine, pyridoxine, biotin and riboflavin were 8, 0.015, 0.4, 0.04 and 0.1 mg/L, respectively, the concentration and yield to glucose of pyruvic acid reached 52.4 g/L and 0.525 g/g at 48 h in flask culture, respectively. Batch culture was conducted in a 2.5 L fermentor with initial glucose concentration of 120 g/L. By adopting the optimal concentration combination of vitamins, the concentration and yield to glucose of pyruvic acid reached 69.4 g/L and 0.593 g/g at 57.5 h, which were increased by 32.4% and 13% than the best results in flask culture, respectively. PMID:12548766

  15. Groundwater surface water interactions through streambeds and the role of phreatophytes in identifying important recharge zones

    NASA Astrophysics Data System (ADS)

    Ahring, T. S.; Steward, D. R.

    2012-06-01

    Groundwater and surface water interactions within riparian corridors impact the distribution of phreatophytes that tap into groundwater stores. The changes in canopy area of phreatophytes over time is related to changes in depth to groundwater, distance from a stream or river, and hydrologic soil group. Remote sensing was used to determine the location of trees with predevelopment and post-development aerial photography over the Ogallala Aquifer in the central plains of the United States. It was found that once the depth to groundwater becomes greater than about 3 m, tree populations decrease as depth to water increases. This subsequently limited the extent of phreatophytes to within 700 m of the river. It was also found that phreatophytes have a higher likelihood of growing on hydrologic soil groups with higher saturated hydraulic conductivity. Phreatophytes exist along portions of the Arkansas River corridor where significant decreases in groundwater occurred as long as alluvium exists to create perched conditions where trees survive dry periods. Significant decreases (more that 50%) in canopy cover exists along river segments where groundwater declined by more than 10 m, indicating areas with good hydraulic connectivity between surface water and groundwater. Thus, interpretation of changes in phreatophyte distribution using historical and recent aerial photophaphy is important in delineating zones of enhanced recharge where aquifers might be effectively recharged through diversion of surface water runoff.

  16. Extracellular nucleases and extracellular DNA play important roles in Vibrio cholerae biofilm formation

    PubMed Central

    Seper, Andrea; Fengler, Vera H I; Roier, Sandro; Wolinski, Heimo; Kohlwein, Sepp D; Bishop, Anne L; Camilli, Andrew; Reidl, Joachim; Schild, Stefan

    2011-01-01

    Biofilms are a preferred mode of survival for many microorganisms including Vibrio cholerae, the causative agent of the severe secretory diarrhoeal disease cholera. The ability of the facultative human pathogen V. cholerae to form biofilms is a key factor for persistence in aquatic ecosystems and biofilms act as a source for new outbreaks. Thus, a better understanding of biofilm formation and transmission of V. cholerae is an important target to control the disease. So far the Vibrio exopolysaccharide was the only known constituent of the biofilm matrix. In this study we identify and characterize extracellular DNA as a component of the Vibrio biofilm matrix. Furthermore, we show that extracellular DNA is modulated and controlled by the two extracellular nucleases Dns and Xds. Our results indicate that extracellular DNA and the extracellular nucleases are involved in diverse processes including the development of a typical biofilm architecture, nutrient acquisition, detachment from biofilms and the colonization fitness of biofilm clumps after ingestion by the host. This study provides new insights into biofilm development and transmission of biofilm-derived V. cholerae. PMID:22032623

  17. Mineralization of naphtenic acids with thermally-activated persulfate: The important role of oxygen.

    PubMed

    Xu, Xiyan; Pliego, Gema; Zazo, Juan A; Casas, Jose A; Rodriguez, Juan J

    2016-11-15

    This study reports on the mineralization of model naphtenic acids (NAs) in aqueous solution by catalyst-free thermally-activated persulfate (PS) oxidation. These species are found to be pollutants in oil sands process-affected waters. The NAs tested include saturated-ring (cyclohexanecarboxylic and cyclohexanebutyric acids) and aromatic (2-naphthoic and 1,2,3,4-tetrahydro-2-naphthoic acids) structures, at 50mgL(-1)starting concentration. The effect of PS dose within a wide range (10-100% of the theoretical stoichiometric) and working temperature (40-97°C) was investigated. At 80°C and intitial pH=8 complete mineralization of the four NAs was achieved with 40-60% of the stoichiometric PS dose. This is explained because of the important contribution of oxygen, which was experimentally verified and was found to be more effective toward the NAs with a single cyclohexane ring than for the bicyclic aromatic-ring-bearing ones. The effect of chloride and bicarbonate was also checked. The former showed negative effect on the degradation rate of NAs whereas it was negligible or even positive for bicarbonate. The rate of mineralization was well described by simple pseudo-first order kinetics with values of the rate constants normalized to the PS dose within the range of 0.062-0.099h(-1). Apparent activation energy values between 93.7-105.3kJmol(-1) were obtained. PMID:27442986

  18. The Disconnect Between Journalism and Science and its Role in Public Misunderstanding of Important Scientific Issues

    NASA Astrophysics Data System (ADS)

    Yulsman, T.

    2006-12-01

    Research shows that Americans' knowledge of science is sorely inaccurate. U.S. adults get most of their knowledge from the popular media, so it has been claimed that problems with media coverage of science are to blame. But this is a simplistic analysis. At their roots, scientific and journalistic modes of inquiry actually share two important normative standards: empiricism and skepticism. On the other hand, news and new scientific knowledge are two very different things. News gathering is guided in large measure by criteria that help journalists decide what is worth covering, as well as by standards of fairness and balance. The overarching goal is to report on things considered newsworthy in a neutral manner. In science, the goal is to ruthlessly discard incorrect ideas to get at the truth about nature. This talk will examine the "good" -- the normative standards that journalists and scientists share, as well as the "bad" -- how the significant disconnects between science and journalism may be contributing to a lack of public understanding of critical scientific issues such as climate change. Among the questions that will be addressed: How do journalists decide what is news? How does science fare when these newsworthiness standards are applied to it? How does the journalistic standard of balance result in inaccurate reporting on climate change? And how might we improve the situation by enhancing communication between scientists and journalist?

  19. Important role of indels in somatic mutations of human cancer genes

    PubMed Central

    2010-01-01

    Background Cancer is clonal proliferation that arises owing to mutations in a subset of genes that confer growth advantage. More and more cancer related genes are found to have accumulated somatic mutations. However, little has been reported about mutational patterns of insertions/deletions (indels) in these genes. Results We analyzed indels' abundance and distribution, the relative ratio between indels and somatic base substitutions and the association between those two forms of mutations in a large number of somatic mutations in the Catalogue of Somatic Mutations in Cancer database. We found a strong correlation between indels and base substitutions in cancer-related genes and showed that they tend to concentrate at the same locus in the coding sequences within the same samples. More importantly, a much higher proportion of indels were observed in somatic mutations, as compared to meiotic ones. Furthermore, our analysis demonstrated a great diversity of indels at some loci of cancer-related genes. Particularly in the genes with abundant mutations, the proportion of 3n indels in oncogenes is 7.9 times higher than that in tumor suppressor genes. Conclusions There are three distinct patterns of indel distribution in somatic mutations: high proportion, great abundance and non-random distribution. Because of the great influence of indels on gene function (e.g., the effect of frameshift mutation), these patterns indicate that indels are frequently under positive selection and can often be the 'driver mutations' in oncogenesis. Such driver forces can better explain why much less frameshift mutations are in oncogenes while much more in tumor suppressor genes, because of their different function in oncogenesis. These findings contribute to our understanding of mutational patterns and the relationship between indels and cancer. PMID:20807447

  20. The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

    PubMed Central

    Soutourina, Olga; Dubrac, Sarah; Poupel, Olivier; Msadek, Tarek; Martin-Verstraete, Isabelle

    2010-01-01

    We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a ΔcymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the ΔcymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the ΔcymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host. PMID:20485570

  1. Role of the epistemic subject in Piaget's genetic epistemology and its importance for science education

    NASA Astrophysics Data System (ADS)

    Niaz, Mansoor

    , attempts to build a general model applicable across types of situations/subjects. The distinction between the epistemic and the psychological subjects is important not for defending Piaget's theory (which has serious theoretical flaws) but to understand epistemic transitions, for example, the one between Piaget's epistemic subject and Pascual-Leone's metasubject. It is concluded that failure to understand the distinction between the epistemic and the psychological subjects would lead to misconstruing the significance of our research findings and, what is more serious, to a lack of a historical perspective.

  2. Phylogenetic Analyses and Characterization of RNase X25 from Drosophila melanogaster Suggest a Conserved Housekeeping Role and Additional Functions for RNase T2 Enzymes in Protostomes

    PubMed Central

    Ambrosio, Linda; Bailey, Ryan; Ding, Jian; MacIntosh, Gustavo C.

    2014-01-01

    Ribonucleases belonging to the RNase T2 family are enzymes associated with the secretory pathway that are almost absolutely conserved in all eukaryotes. Studies in plants and vertebrates suggest they have an important housekeeping function in rRNA recycling. However, little is known about this family of enzymes in protostomes. We characterized RNase X25, the only RNase T2 enzyme in Drosophila melanogaster. We found that RNase X25 is the major contributor of ribonuclease activity in flies as detected by in gel assays, and has an acidic pH preference. Gene expression analyses showed that the RNase X25 transcript is present in all adult tissues and developmental stages. RNase X25 expression is elevated in response to nutritional stresses; consistent with the hypothesis that this enzyme has a housekeeping role in recycling RNA. A correlation between induction of RNase X25 expression and autophagy was observed. Moreover, induction of gene expression was triggered by oxidative stress suggesting that RNase X25 may have additional roles in stress responses. Phylogenetic analyses of this family in protostomes showed that RNase T2 genes have undergone duplication events followed by divergence in several phyla, including the loss of catalytic residues, and suggest that RNase T2 proteins have acquired novel functions. Among those, it is likely that a role in host immunosuppression evolved independently in several groups, including parasitic Platyhelminthes and parasitoid wasps. The presence of only one RNase T2 gene in the D. melanogaster genome, without any other evident secretory RNase activity detected, makes this organism an ideal system to study the cellular functions of RNase T2 proteins associated with RNA recycling and maintenance of cellular homeostasis. On the other hand, the discovery of gene duplications in several protostome genomes also presents interesting new avenues to study additional biological functions of this ancient family of proteins. PMID:25133712

  3. The Potential Role of Motor Unit Number Estimation as an Additional Diagnostic and Prognostic Value in Canine Neurology

    PubMed Central

    Kauder, Julia; Petri, Susanne; Tipold, Andrea; Stein, Veronika M.

    2015-01-01

    Motor unit number estimation (MUNE) is an electrophysiological technique to assess the number of motor units innervating a single muscle or muscle group of interest. It may quantify axonal loss in any disease involving injury or degeneration of ventral horn cells or motor axons. Since MUNE has rarely been used in veterinary medicine, our study aimed to evaluate its potential role as an additional diagnostic and prognostic parameter in canine neurology. Therefore, we examined five healthy dogs and seven dogs suffering from diseases that necessitated general anesthesia for further diagnostics and treatment and that were not expected to interfere with the results of electrodiagnostic testing. By using the incremental technique to study MUNE in the cranial tibial muscle, we determined the number of motor units, the size of the compound muscle action potential, and the mean size of individual motor unit potentials of each dog as well as the mean values for each group. Moreover, we studied the correlation between these parameters. Taking the results into consideration, we addressed the difficulties and limitations of this technique. We, furthermore, pointed out possible fields of application for MUNE in canine neurology, and emphasized several aspects that future studies should focus on when applying MUNE to canine patients. PMID:26664980

  4. The role of prop-1-ene-1,3-sultone as an additive in lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Self, Julian; Hall, David S.; Madec, Lénaïc; Dahn, J. R.

    2015-12-01

    Density functional theory (DFT) is used in conjunction with experimental results to propose decomposition pathways that describe the role and ultimate fate of the PES additive in Li-ion batteries. Oxidation of PES produces carbonyl sulfide gas and ethene at the positive electrode, both experimentally observed byproducts. However, the calculated standard potential for simple PES oxidation, E0ox ∼ 6.7 V vs. Li/Li+, is quite high, suggesting this pathway is unlikely. A "reactive electrode model" is presented, in which the positive electrode material is a reagent in the pseudo-combustion of PES (and other solvents). This spontaneous process produces carbonyl sulfide, carbon dioxide, and a rock salt surface layer, all of which are experimentally observed. At the negative electrode, the reduction of PES occurs via two one-electron steps, where E0red,1 = 0.9 V and E0red,2 = 4.3 V. The reduced species, Li2PES, can react with hydrogen and methyl radicals to produce propene, methylpropene, propane and lithium sulfite. Nucleophilic Li2PES can also react with electrophilic PES, ethylene carbonate, or ethyl methyl carbonate. Eighteen possible organic sulphate 'building blocks' for the solid-electrolyte interphase (SEI) are presented. X-ray photoelectron spectroscopy (XPS) measurements demonstrate that PES reduction indeed results in both lithium sulfite and organic sulphate SEI components.

  5. Additional stratifications in the equatorial F region at dawn and dusk during geomagnetic storms: Role of electrodynamics

    NASA Astrophysics Data System (ADS)

    Sreeja, V.; Balan, N.; Ravindran, Sudha; Pant, Tarun Kumar; Sridharan, R.; Bailey, G. J.

    2009-08-01

    The role of electrodynamics in producing additional stratifications in the equatorial F region (F 3 layer) at dawn and dusk during geomagnetic storms is discussed. Two cases of F 3 layer at dawn (0600-0730 LT on 5 October 2000 and 8 December 2000) and one case of F 3 layer at dusk (1600-1730 LT on 5 October 2000) are observed, for the first time, by the digital ionosonde at the equatorial station Trivandrum (8.5°N 77°E dip ˜ 0.5°N) in India. The unusual F 3 layers occurred during the geomagnetic storms and are associated with southward turning of interplanetary magnetic field B z , suggesting that eastward prompt penetration electric field could be the main cause of the F 3 layers. The dawn F 3 layer on 5 October is modeled using the Sheffield University Plasmasphere-Ionosphere Model by using the E × B drift estimated from the real height variation of the ionospheric peak during the morning period. The model qualitatively reproduces the dawn F 3 layer. While the existing F 2 layer rapidly drifts upward and forms the F 3 layer and topside ledge, a new layer forming at lower heights develops into the normal F 2 layer.

  6. Multiple sulfur isotopes in Paleoarchean barites identify an important role for microbial sulfate reduction in the early marine environment

    NASA Astrophysics Data System (ADS)

    Roerdink, Desiree L.; Mason, Paul R. D.; Farquhar, James; Reimer, Thomas

    2012-05-01

    Bedded barites from the Barberton greenstone belt (South Africa and Swaziland) preserve a comprehensive record of atmospheric, oceanic and microbial processes involved in the formation and evolution of the Paleoarchean (3.6-3.2 Ga) oceanic sulfate reservoir. Here, we report multiple sulfur isotopic compositions from four of these barite occurrences. Relatively constant mass-independent signatures (Δ36S/Δ33S = - 1.0 ± 0.2) within deposits support an important role for atmospheric photolysis in the production of oxidized sulfur, whereas 34S enrichments relative to the inferred composition of photolytic sulfate suggest drawdown of 34S by microbial sulfate reduction. Strong compositional overlap with barites from India and Western Australia indicates the presence of a large-scale and well-mixed marine sulfate pool. Covariation between δ34S and Δ33S within individual deposits also suggests a role for processes occurring in semi-closed basins fed by this global reservoir. Based on modeling results, we interpret variations in δ34S by local microbial sulfate reduction and correlations with Δ33S by weak inputs of sulfur from magmatic sources, microbial sulfide oxidation or sulfur disproportionation. This agrees with the early occurrence of sulfate reducers in the geological record as inferred from published microscopic pyrite data, and identifies their role as important in both global oceans and local basins in the Paleoarchean.

  7. Keratinocytes promote proliferation and inhibit apoptosis of the underlying fibroblasts: an important role in the pathogenesis of keloid.

    PubMed

    Funayama, Emi; Chodon, Thinle; Oyama, Akihiko; Sugihara, Tsuneki

    2003-12-01

    Interactions between epidermal keratinocytes and dermal fibroblasts play an important role in regulating tissue homeostasis and repair. Nevertheless, little is known about the role of keratinocytes in the pathogenesis of keloid. In this study, we investigated the influence of normal skin- and keloid-derived keratinocytes on normal skin- and keloid-derived fibroblasts utilizing a serum-free indirect coculture system. The keloid-derived fibroblasts showed a greater proliferation and minimal apoptosis when cocultured with normal skin- or keloid-derived keratinocytes, and the results were most significant in the latter. This difference was not observed when the fibroblasts were treated with conditioned medium obtained from normal skin- and keloid-derived keratinocytes. Nevertheless, conditioned medium-treated groups showed more proliferation and less apoptosis compared to the nonconditioned medium-treated control groups. We also analyzed the profile of factors involved in cell growth and apoptosis in fibroblasts cocultured with keratinocytes. Extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylations and expression of Bcl-2 and transforming growth factor-beta1 were all significantly upregulated in the fibroblasts cocultured with keloid-derived keratinocytes. Together, these results strongly suggest that the overlying keratinocytes of the keloid lesion play an important role in keloidogenesis by promoting more proliferation and less apoptosis in the underlying fibroblasts through paracrine and double paracrine effects. PMID:14675177

  8. Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import.

    PubMed

    Paila, Yamuna D; Richardson, Lynn Gl; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

    2016-01-01

    Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. PMID:26999824

  9. Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import

    PubMed Central

    Paila, Yamuna D; Richardson, Lynn GL; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

    2016-01-01

    Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. DOI: http://dx.doi.org/10.7554/eLife.12631.001 PMID:26999824

  10. Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections

    PubMed Central

    Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

    2015-01-01

    Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters. PMID:25714877

  11. DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium.

    PubMed

    Dieterich, Lothar C; Klein, Sarah; Mathelier, Anthony; Sliwa-Primorac, Adriana; Ma, Qiaoli; Hong, Young-Kwon; Shin, Jay W; Hamada, Michito; Lizio, Marina; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O; Arner, Erik; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R R; Wasserman, Wyeth W; Detmar, Michael

    2015-11-17

    VEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of lymphatic progenitor cells from embryonic veins and maintaining the expression of PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene expression is still not completely understood. We used cap analysis of gene expression (CAGE) RNA sequencing to characterize the transcriptional changes invoked by VEGF-C in LECs and to identify the transcription factors (TFs) involved. We found that MAFB, a TF involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C. MAFB induced expression of PROX1 as well as other TFs and markers of differentiated LECs, indicating a role in the maintenance of the mature LEC phenotype. Correspondingly, E14.5 Mafb(-/-) embryos showed impaired lymphatic patterning in the skin. This suggests that MAFB is an important TF involved in lymphangiogenesis. PMID:26549461

  12. Deep sequencing reveals important roles of microRNAs in response to drought and salinity stress in cotton.

    PubMed

    Xie, Fuliang; Wang, Qinglian; Sun, Runrun; Zhang, Baohong

    2015-02-01

    Drought and salinity are two major environmental factors adversely affecting plant growth and productivity. However, the regulatory mechanism is unknown. In this study, the potential roles of small regulatory microRNAs (miRNAs) in cotton response to those stresses were investigated. Using next-generation deep sequencing, a total of 337 miRNAs with precursors were identified, comprising 289 known miRNAs and 48 novel miRNAs. Of these miRNAs, 155 miRNAs were expressed differentially. Target prediction, Gene Ontology (GO)-based functional classification, and Kyoto Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment show that these miRNAs might play roles in response to salinity and drought stresses through targeting a series of stress-related genes. Degradome sequencing analysis showed that at least 55 predicted target genes were further validated to be regulated by 60 miRNAs. CitationRank-based literature mining was employed to determinhe the importance of genes related to drought and salinity stress. The NAC, MYB, and MAPK families were ranked top under the context of drought and salinity, indicating their important roles for the plant to combat drought and salinity stress. According to target prediction, a series of cotton miRNAs are associated with these top-ranked genes, including miR164, miR172, miR396, miR1520, miR6158, ghr-n24, ghr-n56, and ghr-n59. Interestingly, 163 cotton miRNAs were also identified to target 210 genes that are important in fibre development. These results will contribute to cotton stress-resistant breeding as well as understanding fibre development. PMID:25371507

  13. Deep sequencing reveals important roles of microRNAs in response to drought and salinity stress in cotton

    PubMed Central

    Xie, Fuliang; Wang, Qinglian; Sun, Runrun; Zhang, Baohong

    2015-01-01

    Drought and salinity are two major environmental factors adversely affecting plant growth and productivity. However, the regulatory mechanism is unknown. In this study, the potential roles of small regulatory microRNAs (miRNAs) in cotton response to those stresses were investigated. Using next-generation deep sequencing, a total of 337 miRNAs with precursors were identified, comprising 289 known miRNAs and 48 novel miRNAs. Of these miRNAs, 155 miRNAs were expressed differentially. Target prediction, Gene Ontology (GO)-based functional classification, and Kyoto Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment show that these miRNAs might play roles in response to salinity and drought stresses through targeting a series of stress-related genes. Degradome sequencing analysis showed that at least 55 predicted target genes were further validated to be regulated by 60 miRNAs. CitationRank-based literature mining was employed to determinhe the importance of genes related to drought and salinity stress. The NAC, MYB, and MAPK families were ranked top under the context of drought and salinity, indicating their important roles for the plant to combat drought and salinity stress. According to target prediction, a series of cotton miRNAs are associated with these top-ranked genes, including miR164, miR172, miR396, miR1520, miR6158, ghr-n24, ghr-n56, and ghr-n59. Interestingly, 163 cotton miRNAs were also identified to target 210 genes that are important in fibre development. These results will contribute to cotton stress-resistant breeding as well as understanding fibre development. PMID:25371507

  14. A dominant role of oxygen additive on cold atmospheric-pressure He + O{sub 2} plasmas

    SciTech Connect

    Yang, Aijun; Liu, Dingxin E-mail: xhw@mail.xjtu.edu.cn; Rong, Mingzhe; Wang, Xiaohua E-mail: xhw@mail.xjtu.edu.cn; Kong, Michael G.

    2014-08-15

    We present in this paper how oxygen additive impacts on the cold atmospheric-pressure helium plasmas by means of a one-dimensional fluid model. For the oxygen concentration [O{sub 2}] > ∼0.1%, the influence of oxygen on the electron characteristics and the power dissipation becomes important, e.g., the electron density, the electron temperature in sheath, the electron-coupling power, and the sheath width decreasing by 1.6 to 16 folds with a two-log increase in [O{sub 2}] from 0.1% to 10%. Also the discharge mode evolves from the γ mode to the α mode. The reactive oxygen species are found to peak in the narrow range of [O{sub 2}] = 0.4%–0.9% in the plasmas, similar to their power-coupling values. This applies to their wall fluxes except for those of O* and O{sub 2}{sup −}. These two species have very short lifetimes, thus only when generated in boundary layers within several micrometers next to the electrode can contribute to the fluxes. The dominant reactive oxygen species and the corresponding main reactions are schematically presented, and their relations are quantified for selected applications.

  15. Genetic Analysis of Arabidopsis Mutants Impaired in Plastid Lipid Import Reveals a Role of Membrane Lipids in Chloroplast Division

    SciTech Connect

    Fan, J.; Xu, C.

    2011-03-01

    The biogenesis of photosynthetic membranes in plants relies largely on lipid import from the endoplasmic reticulum (ER) and this lipid transport process is mediated by TGD proteins in Arabidopsis. Such a dependency of chloroplast biogenesis on ER-to-plastid lipid transport was recently exemplified by analyzing double mutants between tgd1-1 or tgd4-3 and fad6 mutants. The fad6 mutants are defective in the desaturation of membrane lipids in chloroplasts and therefore dependent on import of polyunsaturated lipid precursors from the ER for constructing a competent thylakoid membrane system. In support of a critical role of TGD proteins in ER-to-plastid lipid trafficking, we showed that the introduction of the tgd mutations into fad6 mutant backgrounds led to drastic reductions in relative amounts of thylakoid lipids. Moreover, the tgd1-1 fad6 and tgd4-3 fad6 double mutants were deficient in polyunsaturated fatty acids in chloroplast membrane lipids, and severely compromised in the biogenesis of photosynthetic membrane systems. Here we report that these double mutants are severely impaired in chloroplast division. The possible role of membrane lipids in chloroplast division is discussed.

  16. Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

    PubMed

    Cui, Su-Ying; Li, Sheng-Jie; Cui, Xiang-Yu; Zhang, Xue-Qiong; Yu, Bin; Sheng, Zhao-Fu; Huang, Yuan-Li; Cao, Qing; Xu, Ya-Ping; Lin, Zhi-Ge; Yang, Guang; Song, Jin-Zhi; Ding, Hui; Wang, Zi-Jun; Zhang, Yong-He

    2016-02-01

    The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation. PMID:26558357

  17. Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding

    PubMed Central

    Gao, Su; Zhu, Guangjing; Gao, Xuefei; Wu, Donghai; Carrasco, Patricia; Casals, Núria; Hegardt, Fausto G.; Moran, Timothy H.; Lopaschuk, Gary D.

    2011-01-01

    Brain-specific carnitine palmitoyltransferase-1 (CPT-1c) is implicated in CNS control of food intake. In this article, we explore the role of hypothalamic CPT-1c in leptin's anorexigenic actions. We first show that adenoviral overexpression of CPT-1c in hypothalamic arcuate nucleus of rats increases food intake and concomitantly up-regulates orexigenic neuropeptide Y (NPY) and Bsx (a transcription factor of NPY). Then, we demonstrate that this overexpression antagonizes the anorectic actions induced by central leptin or compound cerulenin (an inhibitor of fatty acid synthase). The overexpression of CPT-1c also blocks leptin-induced down-regulations of NPY and Bsx. Furthermore, the anorectic actions of central leptin or cerulenin are impaired in mice with brain CPT-1c deleted. Both anorectic effects require elevated levels of hypothalamic arcuate nucleus (Arc) malonyl-CoA, a fatty acid-metabolism intermediate that has emerged as a mediator in hypothalamic control of food intake. Thus, these data suggest that CPT-1c is implicated in malonyl-CoA action in leptin's hypothalamic anorectic signaling pathways. Moreover, ceramide metabolism appears to play a role in leptin's central control of feeding. Leptin treatment decreases Arc ceramide levels, with the decrease being important in leptin-induced anorectic actions and down-regulations of NPY and Bsx. Of interest, our data indicate that leptin impacts ceramide metabolism through malonyl-CoA and CPT-1c, and ceramide de novo biosynthesis acts downstream of both malonyl-CoA and CPT-1c in mediating their effects on feeding and expressions of NPY and Bsx. In summary, we provide insights into the important roles of malonyl-CoA, CPT-1c, and ceramide metabolism in leptin's hypothalamic signaling pathways. PMID:21593415

  18. Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding.

    PubMed

    Gao, Su; Zhu, Guangjing; Gao, Xuefei; Wu, Donghai; Carrasco, Patricia; Casals, Núria; Hegardt, Fausto G; Moran, Timothy H; Lopaschuk, Gary D

    2011-06-01

    Brain-specific carnitine palmitoyltransferase-1 (CPT-1c) is implicated in CNS control of food intake. In this article, we explore the role of hypothalamic CPT-1c in leptin's anorexigenic actions. We first show that adenoviral overexpression of CPT-1c in hypothalamic arcuate nucleus of rats increases food intake and concomitantly up-regulates orexigenic neuropeptide Y (NPY) and Bsx (a transcription factor of NPY). Then, we demonstrate that this overexpression antagonizes the anorectic actions induced by central leptin or compound cerulenin (an inhibitor of fatty acid synthase). The overexpression of CPT-1c also blocks leptin-induced down-regulations of NPY and Bsx. Furthermore, the anorectic actions of central leptin or cerulenin are impaired in mice with brain CPT-1c deleted. Both anorectic effects require elevated levels of hypothalamic arcuate nucleus (Arc) malonyl-CoA, a fatty acid-metabolism intermediate that has emerged as a mediator in hypothalamic control of food intake. Thus, these data suggest that CPT-1c is implicated in malonyl-CoA action in leptin's hypothalamic anorectic signaling pathways. Moreover, ceramide metabolism appears to play a role in leptin's central control of feeding. Leptin treatment decreases Arc ceramide levels, with the decrease being important in leptin-induced anorectic actions and down-regulations of NPY and Bsx. Of interest, our data indicate that leptin impacts ceramide metabolism through malonyl-CoA and CPT-1c, and ceramide de novo biosynthesis acts downstream of both malonyl-CoA and CPT-1c in mediating their effects on feeding and expressions of NPY and Bsx. In summary, we provide insights into the important roles of malonyl-CoA, CPT-1c, and ceramide metabolism in leptin's hypothalamic signaling pathways. PMID:21593415

  19. The Ubiquitin-Proteasome System Plays an Important Role during Various Stages of the Coronavirus Infection Cycle ▿

    PubMed Central

    Raaben, Matthijs; Posthuma, Clara C.; Verheije, Monique H.; te Lintelo, Eddie G.; Kikkert, Marjolein; Drijfhout, Jan W.; Snijder, Eric J.; Rottier, Peter J. M.; de Haan, Cornelis A. M.

    2010-01-01

    The ubiquitin-proteasome system (UPS) is a key player in regulating the intracellular sorting and degradation of proteins. In this study we investigated the role of the UPS in different steps of the coronavirus (CoV) infection cycle. Inhibition of the proteasome by different chemical compounds (i.e., MG132, epoxomicin, and Velcade) appeared to not only impair entry but also RNA synthesis and subsequent protein expression of different CoVs (i.e., mouse hepatitis virus [MHV], feline infectious peritonitis virus, and severe acute respiratory syndrome CoV). MHV assembly and release were, however, not appreciably affected by these compounds. The inhibitory effect on CoV protein expression did not appear to result from a general inhibition of translation due to induction of a cellular stress response by the inhibitors. Stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) generally results in impaired initiation of protein synthesis, but the sensitivity of MHV infection to proteasome inhibitors was unchanged in cells lacking a phosphorylatable eIF2α. MHV infection was affected not only by inhibition of the proteasome but also by interfering with protein ubiquitination. Viral protein expression was reduced in cells expressing a temperature-sensitive ubiquitin-activating enzyme E1 at the restrictive temperature, as well as in cells in which ubiquitin was depleted by using small interfering RNAs. Under these conditions, the susceptibility of the cells to virus infection was, however, not affected, excluding an important role of ubiquitination in virus entry. Our observations reveal an important role of the UPS in multiple steps of the CoV infection cycle and identify the UPS as a potential drug target to modulate the impact of CoV infection. PMID:20484504

  20. The First Extracellular Domain Plays an Important Role in Unitary Channel Conductance of Cx50 Gap Junction Channels

    PubMed Central

    Tong, Xiaoling; Aoyama, Hiroshi; Sudhakar, Swathy; Chen, Honghong; Shilton, Brian H.; Bai, Donglin

    2015-01-01

    Gap junction (GJ) channels provide direct passage for ions and small molecules to be exchanged between neighbouring cells and are crucial for many physiological processes. GJ channels can be gated by transjunctional voltage (known as Vj-gating) and display a wide range of unitary channel conductance (γj), yet the domains responsible for Vj-gating and γj are not fully clear. The first extracellular domain (E1) of several connexins has been shown to line part of their GJ channel pore and play important roles in Vj-gating properties and/or ion permeation selectivity. To test roles of the E1 of Cx50 GJ channels, we generated a chimera, Cx50Cx36E1, where the E1 domain of Cx50 was replaced with that of Cx36, a connexin showing quite distinct Vj-gating and γj from those of Cx50. Detailed characterizations of the chimera and three point mutants in E1 revealed that, although the E1 domain is important in determining γj, the E1 domain of Cx36 is able to effectively function within the context of the Cx50 channel with minor changes in Vj-gating properties, indicating that sequence differences between the E1 domains in Cx36 and Cx50 cannot account for their drastic differences in Vj-gating and γj. Our homology models of the chimera and the E1 mutants revealed that electrostatic properties of the pore-lining residues and their contribution to the electric field in the pore are important factors for the rate of ion permeation of Cx50 and possibly other GJ channels. PMID:26625162

  1. Optimizing benefit from CRT: role of speckle tracking echocardiography, the importance of LV lead position and scar.

    PubMed

    Kydd, Anna C; McCormick, Liam M; Dutka, David P

    2012-09-01

    Cardiac resynchronization therapy is demonstrated to be effective in patients with advanced heart failure. Correcting mechanical dyssynchrony is proposed as the predominant mechanism of response. Achieving optimum left ventricular lead position, at the site of maximal mechanical dyssynchrony but away from transmural scar, is identified as one of the main determinants of both symptomatic and prognostic benefit. Strategies employing multimodality cardiac imaging techniques have been used to identify this optimal pacing site, in addition to any potential anatomical limitations to successful implantation. Speckle tracking echocardiography offers prospective lead targeting, incorporating pathophysiological determinants of cardiac resynchronization therapy response. This review considers the key factors in defining optimum left ventricular lead location, emphasizing the role of myocardial scar. The use of speckle tracking echocardiography and the potential for this technique to be incorporated into routine practice to guide the implant strategy in an individual patient is discussed. PMID:23116079

  2. Carbon nanotubes play an important role in the spatial arrangement of calcium deposits in hydrogels for bone regeneration.

    PubMed

    Cancian, Giulia; Tozzi, Gianluca; Hussain, Amirul Ashraf Bin; De Mori, Arianna; Roldo, Marta

    2016-08-01

    Age related bone diseases such as osteoporosis are considered among the main causes of reduced bone mechanical stability and bone fractures. In order to restore both biological and mechanical function of diseased/fractured bones, novel bioactive scaffolds that mimic the bone structure are constantly under development in tissue engineering applications. Among the possible candidates, chitosan-based thermosensitive hydrogel scaffolds represent ideal systems due to their biocompatibility, biodegradability, enhanced antibacterial properties, promotion of osteoblast formation and ease of injection, which makes them suitable for less invasive surgical procedures. As a main drawback, these chitosan systems present poor mechanical performance that could not support load-bearing applications. In order to produce more mechanically-competent biomaterials, the combined addition of hydroxyapatite and carbon nanotubes (CNTs) is proposed in this study. Specifically, the aim of this work is to develop thermosensitive chitosan hydrogels containing stabilised single-walled and multi-walled CNTs, where their effect on the mechanical/physiochemical properties, calcium deposition patterns and ability to provide a platform for the controlled release of protein drugs was investigated. It was found that the addition of CNTs had a significant effect on the sol-gel transition time and significantly increased the resistance to compression for the hydrogels. Moreover, in vitro calcification studies revealed that CNTs played a major role in the spatial arrangements of newly formed calcium deposits in the composite materials studied, suggesting that they may have a role in the way the repair of fragile and/or fractured bones occurs in vivo. PMID:27324780

  3. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state.

    PubMed

    Kurutas, Ergul Belge

    2016-01-01

    Remarkable interest has risen in the idea that oxidative/nitrosative stress is mediated in the etiology of numerous human diseases. Oxidative/Nitrosative stress is the result of an disequilibrium in oxidant/antioxidant which reveals from continuous increase of Reactive Oxygen and Reactive Nitrogen Species production. The aim of this review is to emphasize with current information the importance of antioxidants which play the role in cellular responce against oxidative/nitrosative stress, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue. Products of lipid peroxidation have commonly been used as biomarkers of oxidative/nitrosative stress damage. Lipid peroxidation generates a variety of relatively stable decomposition end products, mainly α, β-unsaturated reactive aldehydes, such as malondialdehyde, 4-hydroxy-2-nonenal, 2-propenal (acrolein) and isoprostanes, which can be measured in plasma and urine as an indirect index of oxidative/nitrosative stress. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative/nitrosative stress or its consequences. They may act from directly scavenging free radicals to increasing antioxidative defences. Antioxidant deficiencies can develop as a result of decreased antioxidant intake, synthesis of endogenous enzymes or increased antioxidant utilization. Antioxidant supplementation has become an increasingly popular practice to maintain optimal body function. However, antoxidants exhibit pro-oxidant activity depending on the specific set of conditions. Of particular importance are their dosage and redox conditions in the cell. PMID:27456681

  4. Differential stemflow yield from European beech saplings: the role and respective importance of individual canopy structure metrics

    NASA Astrophysics Data System (ADS)

    Levia, Delphis; Michalzik, Beate

    2013-04-01

    Stemflow yield from individual trees varies as a function of both meteorological conditions and canopy structure. The importance and differential effects of various metrics of canopy structure in relation to stemflow yield is inadequately understood and the subject of debate among forest hydrologists. It is possible to evaluate the role and respective importance of individual canopy structure metrics by holding meteorological conditions constant. Twelve isolated experimental European beech (Fagus sylvatica L.) saplings in Jena, Germany were exposed to identical meteorological conditions to examine the effects of canopy structure on stemflow production during the 2012 growing season. The canopy structure metrics being evaluated include: trunk diameter, trunk lean, tree height, projected crown area, branch inclination angle, branch count, and biomass (foliar and woody). Principal components analysis and multiple regression are utilized to determine the relative importance of different canopy structure metrics on stemflow yield. Experimental results will provide insight as to which metrics of canopy structure most strongly govern stemflow production. Ultimately, with a more thorough understanding of the unique contributions of various canopy structural metrics to stemflow yield, a useful conceptual guide of stemflow generation can be formulated on the basis of canopy structure for management purposes. Sponsor note: This research was funded by the Alexander von Humboldt Foundation.

  5. The transporter GAT1 plays an important role in GABA-mediated carbon-nitrogen interactions in Arabidopsis

    PubMed Central

    Batushansky, Albert; Kirma, Menny; Grillich, Nicole; Pham, Phuong A.; Rentsch, Doris; Galili, Gad; Fernie, Alisdair R.; Fait, Aaron

    2015-01-01

    Glutamate derived γ-aminobutyric acid (GABA) is synthetized in the cytosol prior to delivery to the mitochondria where it is catabolized via the TCA cycle. GABA accumulates under various environmental conditions, but an increasing number of studies show its involvement at the crossroad between C and N metabolism. To assess the role of GABA in modulating cellular metabolism, we exposed seedlings of A. thaliana GABA transporter gat1 mutant to full nutrition medium and media deficient in C and N combined with feeding of different concentrations (0.5 and 1 mM) of exogenous GABA. GC-MS based metabolite profiling showed an expected effect of medium composition on the seedlings metabolism of mutant and wild type alike. That being said, a significant interaction between GAT1 deficiency and medium composition was determined with respect to magnitude of change in relative amino acid levels. The effect of exogenous GABA treatment on metabolism was contingent on both the medium and the genotype, leading for instance to a drop in asparagine under full nutrition and low C conditions and glucose under all tested media, but not to changes in GABA content. We additionally assessed the effect of GAT1 deficiency on the expression of glutamate metabolism related genes and genes involved in abiotic stress responses. These results suggest a role for GAT1 in GABA-mediated metabolic alterations in the context of the C-N equilibrium of plant cells. PMID:26483804

  6. Specific Subunits of Heterotrimeric G Proteins Play Important Roles during Nodulation in Soybean1[W][OA

    PubMed Central

    Choudhury, Swarup Roy; Pandey, Sona

    2013-01-01

    Heterotrimeric G proteins comprising Gα, Gβ, and Gγ subunits regulate many fundamental growth and development processes in all eukaryotes. Plants possess a relatively limited number of G-protein components compared with mammalian systems, and their detailed functional characterization has been performed mostly in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). However, the presence of single Gα and Gβ proteins in both these species has significantly undermined the complexity and specificity of response regulation in plant G-protein signaling. There is ample pharmacological evidence for the role of G proteins in regulation of legume-specific processes such as nodulation, but the lack of genetic data from a leguminous species has restricted its direct assessment. Our recent identification and characterization of an elaborate G-protein family in soybean (Glycine max) and the availability of appropriate molecular-genetic resources have allowed us to directly evaluate the role of G-protein subunits during nodulation. We demonstrate that all G-protein genes are expressed in nodules and exhibit significant changes in their expression in response to Bradyrhizobium japonicum infection and in representative supernodulating and nonnodulating soybean mutants. RNA interference suppression and overexpression of specific G-protein components results in lower and higher nodule numbers, respectively, validating their roles as positive regulators of nodule formation. Our data further show preferential usage of distinct G-protein subunits in the presence of an additional signal during nodulation. Interestingly, the Gα proteins directly interact with the soybean nodulation factor receptors NFR1α and NFR1β, suggesting that the plant G proteins may couple with receptors other than the canonical heptahelical receptors common in metazoans to modulate signaling. PMID:23569109

  7. GhCFE1A, a dynamic linker between the ER network and actin cytoskeleton, plays an important role in cotton fibre cell initiation and elongation

    PubMed Central

    Lv, Fenni; Wang, Haihai; Wang, Xinyu; Han, Libo; Ma, Yinping; Wang, Sen; Feng, Zhidi; Niu, Xiaowei; Cai, Caiping; Kong, Zhaosheng; Zhang, Tianzhen; Guo, Wangzhen

    2015-01-01

    Fibre cell initiation and elongation is critical for cotton fibre development. However, little is known about the regulation of initiation and elongation during fibre cell development. Here, the regulatory role of a novel protein GhCFE1A was uncovered. GhCFE1A is preferentially expressed at initiation and rapid elongation stages during fibre development; in addition, much higher expression of GhCFE1A was detected at the fibre initiation stage in fibreless cotton mutants than in the fibre-bearing TM-1 wild-type. Importantly, overexpression of GhCFE1A in cotton not only delayed fibre cell elongation but also significantly reduced the density of lint and fuzz fibre initials and stem trichomes. Yeast two-hybrid assay showed that GhCFE1A interacted with several actin proteins, and the interaction was further confirmed by co-sedimentation assay. Interestingly, a subcellular localization assay showed that GhCFE1A resided on the cortical endoplasmic reticulum (ER) network and co-localized with actin cables. Moreover, the density of F-actin filaments was shown to be reduced in GhCFE1A-overexpressing fibres at the rapid elongation stage compared with the wild-type control. Taken together, the results demonstrate that GhCFE1A probably functions as a dynamic linker between the actin cytoskeleton and the ER network, and plays an important role in fibre cell initiation and elongation during cotton fibre development. PMID:25609828

  8. Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research, education, and quality control

    PubMed Central

    Malicki, Julian

    2015-01-01

    Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine. PMID:25949219

  9. GhCFE1A, a dynamic linker between the ER network and actin cytoskeleton, plays an important role in cotton fibre cell initiation and elongation.

    PubMed

    Lv, Fenni; Wang, Haihai; Wang, Xinyu; Han, Libo; Ma, Yinping; Wang, Sen; Feng, Zhidi; Niu, Xiaowei; Cai, Caiping; Kong, Zhaosheng; Zhang, Tianzhen; Guo, Wangzhen

    2015-04-01

    Fibre cell initiation and elongation is critical for cotton fibre development. However, little is known about the regulation of initiation and elongation during fibre cell development. Here, the regulatory role of a novel protein GhCFE1A was uncovered. GhCFE1A is preferentially expressed at initiation and rapid elongation stages during fibre development; in addition, much higher expression of GhCFE1A was detected at the fibre initiation stage in fibreless cotton mutants than in the fibre-bearing TM-1 wild-type. Importantly, overexpression of GhCFE1A in cotton not only delayed fibre cell elongation but also significantly reduced the density of lint and fuzz fibre initials and stem trichomes. Yeast two-hybrid assay showed that GhCFE1A interacted with several actin proteins, and the interaction was further confirmed by co-sedimentation assay. Interestingly, a subcellular localization assay showed that GhCFE1A resided on the cortical endoplasmic reticulum (ER) network and co-localized with actin cables. Moreover, the density of F-actin filaments was shown to be reduced in GhCFE1A-overexpressing fibres at the rapid elongation stage compared with the wild-type control. Taken together, the results demonstrate that GhCFE1A probably functions as a dynamic linker between the actin cytoskeleton and the ER network, and plays an important role in fibre cell initiation and elongation during cotton fibre development. PMID:25609828

  10. Importance of Rhodococcus strains in a bacterial consortium degrading a mixture of hydrocarbons, gasoline, and diesel oil additives revealed by metatranscriptomic analysis.

    PubMed

    Auffret, Marc D; Yergeau, Etienne; Labbé, Diane; Fayolle-Guichard, Françoise; Greer, Charles W

    2015-03-01

    A bacterial consortium (Mix3) composed of microorganisms originating from different environments (soils and wastewater) was obtained after enrichment in the presence of a mixture of 16 hydrocarbons, gasoline, and diesel oil additives. After addition of the mixture, the development of the microbial composition of Mix3 was monitored at three different times (35, 113, and 222 days) using fingerprinting method and dominant bacterial species were identified. In parallel, 14 bacteria were isolated after 113 days and identified. Degradation capacities for Mix3 and the isolated bacterial strains were characterized and compared. At day 113, we induced the expression of catabolic genes in Mix3 by adding the substrate mixture to resting cells and the metatranscriptome was analyzed. After addition of the substrate mixture, the relative abundance of Actinobacteria increased at day 222 while a shift between Rhodococcus and Mycobacterium was observed after 113 days. Mix3 was able to degrade 13 compounds completely, with partial degradation of isooctane and 2-ethylhexyl nitrate, but tert-butyl alcohol was not degraded. Rhodococcus wratislaviensis strain IFP 2016 isolated from Mix3 showed almost the same degradation capacities as Mix3: these results were not observed with the other isolated strains. Transcriptomic results revealed that Actinobacteria and in particular, Rhodococcus species, were major contributors in terms of total and catabolic gene transcripts while other species were involved in cyclohexane degradation. Not all the microorganisms identified at day 113 were active except R. wratislaviensis IFP 2016 that appeared to be a major player in the degradation activity observed in Mix3. PMID:25343979

  11. Bulk-like endocytosis plays an important role in the recycling of insulin granules in pancreatic beta cells.

    PubMed

    Wen, Du; Xue, Yanhong; Liang, Kuo; Yuan, Tianyi; Lu, Jingze; Zhao, Wei; Xu, Tao; Chen, Liangyi

    2012-08-01

    Although bulk endocytosis has been found in a number of neuronal and endocrine cells, the molecular mechanism and physiological function of bulk endocytosis remain elusive. In pancreatic beta cells, we have observed bulk-like endocytosis evoked both by flash photolysis and trains of depolarization. Bulk-like endocytosis is a clathrin-independent process that is facilitated by enhanced extracellular Ca(2+) entry and suppressed by the inhibition of dynamin function. Moreover, defects in bulk-like endocytosis are accompanied by hyperinsulinemia in primary beta cells dissociated from diabetic KKAy mice, which suggests that bulk-like endocytosis plays an important role in maintaining the exo-endocytosis balance and beta cell secretory capability. PMID:22729398

  12. Galectin-1 overexpression in endometriosis and its regulation by neuropeptides (CRH, UCN) indicating its important role in reproduction and inflammation.

    PubMed

    Vergetaki, Aikaterini; Jeschke, Udo; Vrekoussis, Thomas; Taliouri, Eirini; Sabatini, Luca; Papakonstanti, Evangelia A; Makrigiannakis, Antonis

    2014-01-01

    Endometriosis is an inflammatory disease of women of reproductive age featured by the presence of ectopic endometrium and is strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found to have pro- or anti-inflammatory roles in the reproductive tract and in pathological conditions concerning infertility. Galectin-1, which is expressed at endometrium and decidua, plays a major role in implantation and trophoblast invasion. Also, the neuropeptides, corticotropin releasing hormone (CRH) and urocortin (UCN) and their receptors are expressed in eutopic and ectopic endometrium showing a differential expression pattern in endometriotic women compared to healthy ones. The aim of this study was to examine the galectin-1 expression in endometriotic lesions and compare its expression in eutopic endometrium of endometriotic and healthy women. Furthermore, we examined the effect of CRH and UCN in galectin-1 expression in Ishikawa cell line and macrophages and investigated the implication of CRHR1 in these responses. Eutopic and ectopic endometrium specimens, Ishikawa cell line and mice macrophages were used. Immunohistochemistry and western blot analysis were performed in order to identify galectin-1 expression in ectopic and eutopic endometrium of women with and without endometriosis and the regulatory effect of CRH and UCN on galectin-1 expression. This study presents for the first time that galectin-1 is overexpressed in endometriotic lesions compared to eutopic endometrium of endometriotic women and is more abundantly expressed in eutopic endometrium of disease women compared to healthy ones. Furthermore, it is shown that CRH and UCN upregulate galectin-1 expression in Ishikawa cell line and macrophages and this effect is mediated through CRHR1. These results suggest that galectin-1 might play an important role in endometriosis pathology and infertility profile of women suffering from endometriosis by being at the same time regulated by CRH

  13. Galectin-1 Overexpression in Endometriosis and Its Regulation by Neuropeptides (CRH, UCN) Indicating Its Important Role in Reproduction and Inflammation

    PubMed Central

    Vergetaki, Aikaterini; Jeschke, Udo; Vrekoussis, Thomas; Taliouri, Eirini; Sabatini, Luca; Papakonstanti, Evangelia A.; Makrigiannakis, Antonis

    2014-01-01

    Endometriosis is an inflammatory disease of women of reproductive age featured by the presence of ectopic endometrium and is strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found to have pro- or anti-inflammatory roles in the reproductive tract and in pathological conditions concerning infertility. Galectin-1, which is expressed at endometrium and decidua, plays a major role in implantation and trophoblast invasion. Also, the neuropeptides, corticotropin releasing hormone (CRH) and urocortin (UCN) and their receptors are expressed in eutopic and ectopic endometrium showing a differential expression pattern in endometriotic women compared to healthy ones. The aim of this study was to examine the galectin-1 expression in endometriotic lesions and compare its expression in eutopic endometrium of endometriotic and healthy women. Furthermore, we examined the effect of CRH and UCN in galectin-1 expression in Ishikawa cell line and macrophages and investigated the implication of CRHR1 in these responses. Eutopic and ectopic endometrium specimens, Ishikawa cell line and mice macrophages were used. Immunohistochemistry and western blot analysis were performed in order to identify galectin-1 expression in ectopic and eutopic endometrium of women with and without endometriosis and the regulatory effect of CRH and UCN on galectin-1 expression. This study presents for the first time that galectin-1 is overexpressed in endometriotic lesions compared to eutopic endometrium of endometriotic women and is more abundantly expressed in eutopic endometrium of disease women compared to healthy ones. Furthermore, it is shown that CRH and UCN upregulate galectin-1 expression in Ishikawa cell line and macrophages and this effect is mediated through CRHR1. These results suggest that galectin-1 might play an important role in endometriosis pathology and infertility profile of women suffering from endometriosis by being at the same time regulated by CRH

  14. Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

    SciTech Connect

    Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

    2014-10-03

    Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.

  15. An Important Role for Mitochondrial Antiviral Signaling Protein in the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle

    PubMed Central

    West, John A.; Wicks, Megan; Gregory, Sean M.; Chugh, Pauline; Jacobs, Sarah R.; Zhang, Zhigang; Host, Kurtis M.; Dittmer, Dirk P.

    2014-01-01

    ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) has been shown to be recognized by two families of pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Here we show that MAVS and RIG-I (retinoic acid-inducible gene 1), an RLR family member, also have a role in suppressing KSHV replication and production. In the context of primary infection, we show that in cells with depleted levels of MAVS or RIG-I, KSHV transcription is increased, while beta interferon (IFN-β) induction is attenuated. We also observed that MAVS and RIG-I are critical during the process of reactivation. Depletion of MAVS and RIG-I prior to reactivation led to increased viral load and production of infectious virus. Finally, MAVS depletion in latent KSHV-infected B cells leads to increased viral gene transcription. Overall, this study suggests a role for MAVS and RIG-I signaling during different stages of the KSHV life cycle. IMPORTANCE We show that RIG-I and its adaptor protein, MAVS, can sense KSHV infection and that these proteins can suppress KSHV replication following primary infection and/or viral reactivation. PMID:24623417

  16. Silencing of the chalcone synthase gene in Casuarina glauca highlights the important role of flavonoids during nodulation.

    PubMed

    Abdel-Lateif, Khalid; Vaissayre, Virginie; Gherbi, Hassen; Verries, Clotilde; Meudec, Emmanuelle; Perrine-Walker, Francine; Cheynier, Véronique; Svistoonoff, Sergio; Franche, Claudine; Bogusz, Didier; Hocher, Valérie

    2013-09-01

    Nitrogen-fixing root nodulation is confined to four plant orders, including > 14,000 Leguminosae, one nonlegume genus Parasponia and c. 200 actinorhizal species that form symbioses with rhizobia and Frankia bacterial species, respectively. Flavonoids have been identified as plant signals and developmental regulators for nodulation in legumes and have long been hypothesized to play a critical role during actinorhizal nodulation. However, direct evidence of their involvement in actinorhizal symbiosis is lacking. Here, we used RNA interference to silence chalcone synthase, which is involved in the first committed step of the flavonoid biosynthetic pathway, in the actinorhizal tropical tree Casuarina glauca. Transformed flavonoid-deficient hairy roots were generated and used to study flavonoid accumulation and further nodulation. Knockdown of chalcone synthase expression reduced the level of specific flavonoids and resulted in severely impaired nodulation. Nodule formation was rescued by supplementing the plants with naringenin, which is an upstream intermediate in flavonoid biosynthesis. Our results provide, for the first time, direct evidence of an important role for flavonoids during the early stages of actinorhizal nodulation. PMID:23692063

  17. Expression of the Human Glucokinase Gene: Important Roles of the 5′ Flanking and Intron 1 Sequences

    PubMed Central

    Li, Zhixin; Mao, Yiqing; Li, Hui; Wang, Xi; Wang, Rong; Xu, Wei; Song, Rongjing; Jin, Ling; Li, Xiuli; Irwin, David M.; Niu, Gang; Tan, Huanran

    2012-01-01

    Background Glucokinase plays important tissue-specific roles in human physiology, where it acts as a sensor of blood glucose levels in the pancreas, and a few other cells of the gut and brain, and as the rate-limiting step in glucose metabolism in the liver. Liver-specific expression is driven by one of the two tissue-specific promoters, and has an absolute requirement for insulin. The sequences that mediate regulation by insulin are incompletely understood. Methodology/Principal Findings To better understand the liver-specific expression of the human glucokinase gene we compared the structures of this gene from diverse mammals. Much of the sequence located between the 5′ pancreatic beta-cell-specific and downstream liver-specific promoters of the glucokinase genes is composed of repetitive DNA elements that were inserted in parallel on different mammalian lineages. The transcriptional activity of the liver-specific promoter 5′ flanking sequences were tested with and without downstream intronic sequences in two human liver cells lines, HepG2 and L-02. While glucokinase liver-specific 5′ flanking sequences support expression in liver cell lines, a sequence located about 2000 bases 3′ to the liver-specific mRNA start site represses gene expression. Enhanced reporter gene expression was observed in both cell lines when cells were treated with fetal calf serum, but only in the L-02 cells was expression enhanced by insulin. Conclusions/Significance Our results suggest that the normal liver L-02 cell line may be a better model to understand the regulation of the liver-specific expression of the human glucokinase gene. Our results also suggest that sequences downstream of the liver-specific mRNA start site have important roles in the regulation of liver-specific glucokinase gene expression. PMID:23029263

  18. Role of import and export regulatory animal health officials in international control and surveillance for animal diseases.

    PubMed

    Bokma, Bob H

    2006-10-01

    The challenges to those who regulate the import and export of animals and animal products are escalating, due to the evolving nature of animal and human disease agents. The diseases and agents of interest may include low pathogenic avian influenza, bluetongue, bovine spongiform encephalopathy, and foot-and-mouth disease. Fear of an incursion of an unknown or incompletely understood threat can significantly limit risk tolerance. The fear may be that an incursion will affect export trade or tourism. An incomplete knowledge of the animal health situation in the exporting country, due to insufficient surveillance for the disease agent of concern, may limit the application of science in import decisions. In addition, the disease agent may be inappropriately considered exotic if it has not been described. As a result, excessive safeguards for disease agents that do not present any new threat may be employed. To confront these challenges, we are striving toward transparency in international reporting. Moreover, regulatory import decisions exceeding the recommendations of the Terrestrial Animal Health Code and the Aquatic Animal Health Code of the World Organization for Animal Health must be fair and science-based. PMID:17135497

  19. Re(de)fining the orthographic neighborhood: the role of addition and deletion neighbors in lexical decision and reading.

    PubMed

    Davis, Colin J; Perea, Manuel; Acha, Joana

    2009-10-01

    The influence of addition and deletion neighbors on visual word identification was investigated in four experiments. Experiments 1 and 2 used Spanish stimuli. In Experiment 1, lexical decision latencies were slower and less accurate for words and nonwords with higher-frequency deletion neighbors (e.g., jugar in juzgar), relative to control stimuli. Experiment 2 showed a similar interference effect for words and nonwords with higher-frequency addition neighbors (e.g., conejo, which has the addition neighbor consejo), relative to control stimuli. Experiment 3 replicated this addition neighbor interference effect in a lexical decision experiment with English stimuli. Across all three experiments, interference effects were always evident for addition/deletion neighbors with word-outer overlap, usually present for those with word-initial overlap, but never present for those with word-final overlap. Experiment 4 replicated the addition/deletion neighbor inhibitory effects in a Spanish sentence reading task in which the participants' eye movements were monitored. These findings suggest that conventional orthographic neighborhood metrics should be redefined. In addition to its methodological implications, this conclusion has significant theoretical implications for input coding schemes and the mechanisms underlying word recognition. PMID:19803656

  20. Sphingosine kinase 1 dependent protein kinase C-δ activation plays an important role in acute liver failure in mice

    PubMed Central

    Lei, Yan-Chang; Yang, Ling-Ling; Li, Wen; Luo, Pan

    2015-01-01

    AIM: To investigate the role of protein kinase C (PKC)-δ activation in the pathogenesis of acute liver failure (ALF) in a well-characterized mouse model of D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced ALF. METHODS: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 μg/kg). Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at different time points within one week were determined using a multiparameteric analyzer. Serum levels of high-mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 as well as nuclear factor (NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot. RESULTS: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-GalN/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group (P < 0.001). Rottlerin treatment also significantly decreased serum levels of HMGB1 at 6, 12, and 24 h, TNF-α, IL-6 and IL-1 β at 12 h compared with the control group (P < 0.01). The inflammatory cell infiltration and necrosis in liver tissue were also decreased in the rottlerin treatment group. Furthermore, sphingosine kinase 1 (SphK1) dependent PKC-δ activation played an important role in promoting NF-κB activation and inflammatory cytokine production in ALF. CONCLUSION: SphK1 dependent PKC-δ activation plays an important role in promoting NF-κB activation and inflammatory response in ALF, and inhibition of PKC-δ activation might be

  1. Molecular identification of three novel glutaredoxin genes that play important roles in antioxidant defense in Helicoverpa armigera.

    PubMed

    Zhang, Song-Dou; Shen, Zhong-Jian; Liu, Xiao-Ming; Li, Zhen; Zhang, Qing-Wen; Liu, Xiao-Xia

    2016-08-01

    Glutaredoxins (Grxs), also known as thioltransferases, play key roles in maintaining intracellular redox balance and protecting cells from oxidative damage in plants and mammals. We tested whether Grxs play important roles in antioxidant defense in insects using the moth, Helicoverpa armigera. We obtained the full-length cDNA sequences of three novel Grx genes, named HaGrx, HaGrx3, and HaGrx5. Sequence analysis indicated that HaGrx shared a high amino acid identity (58%-78%) and a CPYC motif of conserved redox activity with homologues from other selected insect species. In contrast, HaGrx3 and HaGrx5 both shared a CGF(S/G) motif, a conserved catalytic domain, with other orthologous genes. Quantitative real-time PCR results revealed that HaGrx, HaGrx3, and HaGrx5 exhibited temporally- and spatially-dependent patterns of expression. The mRNA expression of HaGrx, HaGrx3, and HaGrx5 was induced by various temperature stresses and H2O2 treatments. We further investigated the knockdown of HaGrx, HaGrx3, and HaGrx5 in H. armigera larvae and found that most of the selected antioxidant genes were up regulated. However, Tpx was down regulated, and further interpretation of the complementary functions of these antioxidant genes is still required. We also determined the effect of HaGrx, HaGrx3, and HaGrx5 knockdown on antioxidant enzymatic activity and metabolite content. The enzymatic activities of SOD, CAT, and POD, and the metabolite contents of hydrogen peroxide, ascorbate, protein carbonyl, and total GSH increased after RNAi mediated knockdown of HaGrx, HaGrx3, and HaGrx5. These results supported our hypothesis that HaGrx, HaGrx3, and HaGrx5 play important roles in antioxidant defense of Helicoverpa armigera and provided a theoretical basis for further in-depth study of physiological function in the insect glutaredoxin family genes. PMID:27339760

  2. The imbalance between TIMP3 and matrix-degrading enzymes plays an important role in intervertebral disc degeneration.

    PubMed

    Li, Yan; Li, Kang; Han, Xiuguo; Mao, Chuanyuan; Zhang, Kai; Zhao, Tengfei; Zhao, Jie

    2016-01-15

    It is well-known that one of the most important features of intervertebral disc degeneration (IDD) is the extracellular matrix (ECM) degradation. Collagen and aggrecan are major components of ECM; the degradation of ECM in intervertebral discs (IVDs) is closely related to the activities of collagenase and aggrecanase. TIMP-3 is the most efficient inhibitor of aggrecanase in IVD. However, only few studies focus on the potential relationship between TIMP-3 and IDD. In our study, we found TIMP-3 gene expression was decreased after stimulating with LPS in rat nucleus pulposus (NP) cells. Then we used a lentivirus vector to reconstruct rat NP cells which high expressed TIMP-3 gene (LV-TIMP3). The upregulation of MMPs and ADAMTSs induced by LPS was significantly inhibited in LV-TIMP3 cells. After overexpression of TIMP-3, the aggrecan breakdown caused by LPS was also reduced in both monolayer culture and three-dimension culture model. To further study the relation between TIMP-3 and IDD, we collected human NP tissue samples of different degenerative degrees. Real-time PCR and immunohistochemical staining showed that the expression of TIMP-3 was negatively correlated with the degree of intervertebral disc degeneration, while MMP-1 and ADAMTS-4 were markedly increased in degenerative IVD. Taken together, our results suggest that the imbalance between aggrecanase and TIMP-3 may play an important role in the pathogenesis of IDD and therefore be a potential therapeutic target for treating IDD. PMID:26686417

  3. W-box and G-box elements play important roles in early senescence of rice flag leaf

    PubMed Central

    Liu, Li; Xu, Wei; Hu, Xuesong; Liu, Haoju; Lin, Yongjun

    2016-01-01

    Plant cis-elements play important roles in global regulation of gene expression. Based on microarray data from rice flag leaves during early senescence, we identified W-box and G-box cis-elements as positive regulators of senescence in the important rice variety Minghui 63. Both cis-elements were bound by leaf senescence-specific proteins in vitro and influenced senescence in vivo. Furthermore, combination of the two elements drove enhanced expression during leaf senescence, and copy numbers of the cis-elements significantly affected the levels of expression. The W-box is the cognate cis-element for WRKY proteins, while the G-box is the cognate cis-element for bZIP, bHLH and NAC proteins. Consistent with this, WRKY, bZIP, bHLH and NAC family members were overrepresented among transcription factor genes up-regulated according during senescence. Crosstalk between ABA, CTK, BR, auxin, GA and JA during senescence was uncovered by comparing expression patterns of senescence up-regulated transcription factors. Together, our results indicate that hormone-mediated signaling could converge on leaf senescence at the transcriptional level through W-box and G-box elements. Considering that there are very few documented early senescence-related cis-elements, our results significantly contribute to understanding the regulation of flag leaf senescence and provide prioritized targets for stay-green trait improvement. PMID:26864250

  4. Proteomic profiling analysis reveals that glutathione system plays important roles responding to osmotic stress in wheat (Triticum aestivum L.) roots.

    PubMed

    Ma, Jianhui; Dong, Wen; Zhang, Daijing; Gao, Xiaolong; Jiang, Lina; Shao, Yun; Tong, Doudou; Li, Chunxi

    2016-01-01

    Wheat is one of the most important crops in the world, and osmotic stress has become one of the main factors affecting wheat production. Understanding the mechanism of the response of wheat to osmotic stress would be greatly significant. In the present study, isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the changes of protein expression in the wheat roots exposed to different osmotic stresses. A total of 2,228 expressed proteins, including 81 differentially expressed proteins, between osmotic stress and control, were found. The comprehensive analysis of these differentially expressed proteins revealed that osmotic stress increased the variety of expressed proteins and suppressed the quantity of expressed proteins in wheat roots. Furthermore, the proteins for detoxifying and reactive oxygen species scavenging, especially the glutathione system, played important roles in maintaining organism balance in response to osmotic stress in wheat roots. Thus, the present study comprehensively describes the protein expression changes in wheat roots in response to osmotic stress, providing firmer foundation to further study the mechanism of osmotic resistance in wheat. PMID:27602297

  5. Proteomic profiling analysis reveals that glutathione system plays important roles responding to osmotic stress in wheat (Triticum aestivum L.) roots

    PubMed Central

    Dong, Wen; Zhang, Daijing; Gao, Xiaolong; Shao, Yun; Tong, Doudou

    2016-01-01

    Wheat is one of the most important crops in the world, and osmotic stress has become one of the main factors affecting wheat production. Understanding the mechanism of the response of wheat to osmotic stress would be greatly significant. In the present study, isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the changes of protein expression in the wheat roots exposed to different osmotic stresses. A total of 2,228 expressed proteins, including 81 differentially expressed proteins, between osmotic stress and control, were found. The comprehensive analysis of these differentially expressed proteins revealed that osmotic stress increased the variety of expressed proteins and suppressed the quantity of expressed proteins in wheat roots. Furthermore, the proteins for detoxifying and reactive oxygen species scavenging, especially the glutathione system, played important roles in maintaining organism balance in response to osmotic stress in wheat roots. Thus, the present study comprehensively describes the protein expression changes in wheat roots in response to osmotic stress, providing firmer foundation to further study the mechanism of osmotic resistance in wheat. PMID:27602297

  6. Nod-Like Receptor Protein-3 Inflammasome Plays an Important Role during Early Stages of Wound Healing

    PubMed Central

    Weinheimer-Haus, Eileen M.; Mirza, Rita E.; Koh, Timothy J.

    2015-01-01

    The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing. PMID:25793779

  7. Genetic Diversity Analysis Reveals that Geographical Environment Plays a More Important Role than Rice Cultivar in Villosiclava virens Population Selection

    PubMed Central

    Wang, Fei; Zhang, Shu; Liu, Mei-Gang; Lin, Xian-Song; Liu, Hui-Jiang; Peng, You-Liang; Lin, Yang; Huang, Jun-Bin

    2014-01-01

    Rice false smut caused by Villosiclava virens is an economically important disease of grains worldwide. The genetic diversity of 153 isolates from six fields located in Wuhan (WH), Yichang Wangjia (YCW), Yichang Yaohe (YCY), Huanggang (HG), Yangxin (YX), and Jingzhou (JZ) in Hubei province of China were phylogenetically analyzed to evaluate the influence of environments and rice cultivars on the V. virens populations. Isolates (43) from Wuhan were from two rice cultivars, Wanxian 98 and Huajing 952, while most of the other isolates from fields YCW, YCY, HG, YX, and JZ originated from different rice cultivars with different genetic backgrounds. Genetic diversity of isolates was analyzed using random amplified polymorphic DNA (RAPD) and single-nucleotide polymorphisms (SNP). The isolates from the same cultivars in Wuhan tended to group together, indicating that the cultivars had an important impact on the fungal population. The 110 isolates from individual fields tended to cluster according to geographical origin. The values of Nei's gene diversity (H) and Shannon's information index (I) showed that the genetic diversity among isolates was higher between than within geographical populations. Furthermore, mean genetic distance between groups (0.006) was higher than mean genetic distance within groups (0.0048) according to MEGA 5.2. The pairwise population fixation index (FST) values also showed significant genetic differentiation between most populations. Higher genetic similarity of isolates from individual fields but different rice cultivars suggested that the geographical factor played a more important role in the selection of V. virens isolates than rice cultivars. This information could be used to improve the management strategy for rice false smut by adjusting the cultivation measures, such as controlling fertilizer, water, and planting density, in the rice field to change the microenvironment. PMID:24584249

  8. Genetic diversity analysis reveals that geographical environment plays a more important role than rice cultivar in Villosiclava virens population selection.

    PubMed

    Wang, Fei; Zhang, Shu; Liu, Mei-Gang; Lin, Xian-Song; Liu, Hui-Jiang; Peng, You-Liang; Lin, Yang; Huang, Jun-Bin; Luo, Chao-Xi

    2014-05-01

    Rice false smut caused by Villosiclava virens is an economically important disease of grains worldwide. The genetic diversity of 153 isolates from six fields located in Wuhan (WH), Yichang Wangjia (YCW), Yichang Yaohe (YCY), Huanggang (HG), Yangxin (YX), and Jingzhou (JZ) in Hubei province of China were phylogenetically analyzed to evaluate the influence of environments and rice cultivars on the V. virens populations. Isolates (43) from Wuhan were from two rice cultivars, Wanxian 98 and Huajing 952, while most of the other isolates from fields YCW, YCY, HG, YX, and JZ originated from different rice cultivars with different genetic backgrounds. Genetic diversity of isolates was analyzed using random amplified polymorphic DNA (RAPD) and single-nucleotide polymorphisms (SNP). The isolates from the same cultivars in Wuhan tended to group together, indicating that the cultivars had an important impact on the fungal population. The 110 isolates from individual fields tended to cluster according to geographical origin. The values of Nei's gene diversity (H) and Shannon's information index (I) showed that the genetic diversity among isolates was higher between than within geographical populations. Furthermore, mean genetic distance between groups (0.006) was higher than mean genetic distance within groups (0.0048) according to MEGA 5.2. The pairwise population fixation index (FST) values also showed significant genetic differentiation between most populations. Higher genetic similarity of isolates from individual fields but different rice cultivars suggested that the geographical factor played a more important role in the selection of V. virens isolates than rice cultivars. This information could be used to improve the management strategy for rice false smut by adjusting the cultivation measures, such as controlling fertilizer, water, and planting density, in the rice field to change the microenvironment. PMID:24584249

  9. The Role of Time- and Space Scales in Estimating the Relative Importance of Isopycnal and Diapycnal Oceanic Mixing

    NASA Astrophysics Data System (ADS)

    Schanze, Julian; Schmitt, Raymond

    2015-04-01

    Large-scale thermal forcing and freshwater fluxes play an essential role in setting the ocean's temperature and salinity. The ratio of the relative contributions of haline and thermal forcing in the mixed layer is maintained by large-scale surface fluxes, leading to important consequences for mixing in the ocean interior. In a stratified ocean, mixing processes can be either isopycnal or diapycnal. The contribution of these processes to the total mixing rate in the ocean can be estimated from the large-scale forcing by evaluating the production of thermal variance, salinity variance and temperature-salinity covariance. A number of surface heat- and freshwater flux estimates are used to evaluate these terms and combine them to generate estimates of the production of density and spice variance. This variance production at the surface is used to estimate the relative importance of isopycnal and diapycnal mixing in the ocean. While isopycnal and diapycnal processes occur on very different length scales, we find that surface-driven production of density and spice variance requires an approximate equipartition between isopycnal and diapycnal mixing in the ocean interior. Here, dissipation estimates are produced using time-mean, monthly and daily flux estimates and surface variables, including Aquarius SSS and Optimum Interpolation SST to elucidate the importance of seasonal and daily forcing. While the inclusion of high-frequency variability increases the total dissipation required, it is likely that much of the resulting variance production is dissipated locally. The increase in diapycnal dissipation is greater than that of isopycnal dissipation, suggesting that more diapycnal dissipation occurs on short space- and time scales.

  10. The glycerophosphoryl diester phosphodiesterase-like proteins SHV3 and its homologs play important roles in cell wall organization.

    PubMed

    Hayashi, Shimpei; Ishii, Tadashi; Matsunaga, Toshiro; Tominaga, Rumi; Kuromori, Takashi; Wada, Takuji; Shinozaki, Kazuo; Hirayama, Takashi

    2008-10-01

    Despite the importance of extracellular events in cell wall organization and biogenesis, the mechanisms and related factors are largely unknown. We isolated an allele of the shaven3 (shv3) mutant of Arabidopsis thaliana, which exhibits ruptured root hair cells during tip growth. SHV3 encodes a novel protein with two tandemly repeated glycerophosphoryl diester phosphodiesterase-like domains and a glycosylphosphatidylinositol anchor, and several of its paralogs are found in Arabidopsis. Here, we report the detailed characterization of mutants of SHV3 and one of its paralogs, SVL1. The shv3 and svl1 double mutant exhibited additional defects, including swollen guard cells, aberrant expansion of the hypocotyl epidermis and ectopic lignin deposits, suggesting decreased rigidity of the cell wall. Fourier-transform infrared spectroscopy and measurement of the cell wall components indicated an altered cellulose content and pectin modification with cross-linking in the double mutant. Furthermore, we found that the ruptured root hair phenotype of shv3 was suppressed by increasing the amount of borate, which is supposed to be involved in pectic polysaccharide cross-linking, in the medium. These findings indicate that SHV3 and its paralogs are novel important factors involved in primary cell wall organization. PMID:18718934

  11. The role of organic compounds in cloud formation: Relative importance of entrainment, co-condensation and particle-phase properties

    NASA Astrophysics Data System (ADS)

    Lowe, Samuel; Partridge, Daniel; Topping, David; Riipinen, Ilona

    2016-04-01

    The organic fraction of atmospheric aerosols is widely acknowledged to affect the cloud nucleating potential of aerosols. Cloud droplet formation through activation of non-volatile CCN is considered to be relatively well understood, however, there are fewer systematic studies on the activation of aerosols containing semi-volatile organic compounds that co-condense alongside water vapour, thus enhancing CCN activity. Although the significance of co-condensation of organic vapours for cloud droplet number concentration predictions has recently been identified, it remains uncertain how this process may interact with atmospheric dynamics. In addition to co-condensation of existing in-cloud material, additional semi-volatile mass can be entrained from the surrounding environment. Reduced cloud droplet number concentrations are expected as the parcel is diluted with clean air; however, additional soluble mass in the particle phase promotes droplet activation. The extent of increased droplet activation due to co-condensation relies also on the physiochemical properties of the organic compounds, as seen in several other phase partitioning sensitivity studies. In this work we study the simultaneous impact of entrainment and co-condensation, the relative importance of these two processes at different atmospheric conditions, their interactions with each other, and the particle-phase chemistry in terms of cloud microphysical properties and their parametric sensitivities. To assess the importance of the entrainment of semi-volatile materials as compared with their co-condensation and chemical properties, a pseudo-adiabatic cloud parcel model with a detailed description of bin microphysics is employed. We have added the co-condensation process to the model such that it is coupled with the parametric entrainment representation. The effects of entrainment and co-condensation are benchmarked independently and simultaneously against a control simulation. Furthermore, we probe the

  12. Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity.

    PubMed

    Tu, Meijuan; Sun, Siyuan; Wang, Kai; Peng, Xueying; Wang, Ruihan; Li, Liping; Zeng, Su; Zhou, Hui; Jiang, Huidi

    2013-09-15

    Monocrotaline (MCT) is a kind of toxic retronecine-type pyrrolizidine alkaloids (PAs) from plants of Crotalaria, which can be bio-activated by cytochrome P450 (CYP) enzymes in liver and then induce hepatotoxicity. Since CYPs are localized in the endoplasmic reticulum, the influx of MCT to the liver is the key step for its hepatotoxicity. The objective of the present study was to investigate the role of organic cation transporter 1 (OCT1), a transporter mainly expressed in liver, in the uptake of MCT and in hepatotoxicity induced by MCT. The results revealed that MCT markedly inhibited the uptake of 1-methyl-4-phenylpyridinium (MPP(+)), an OCT1 substrate, in Madin-Darby canine kidney (MDCK) cells stably expressing human OCT1 (MDCK-hOCT1) with the IC50 of 5.52±0.56μM. The uptake of MCT was significantly higher in MDCK-hOCT1 cells than in MDCK-mock cells, and MCT uptake in MDCK-hOCT1 cells followed Michaelis-Menten kinetics with the Km and Vmax values of 25.0±6.7μM and 266±64pmol/mg protein/min, respectively. Moreover, the OCT1 inhibitors, such as quinidine, d-tetrahydropalmatine (d-THP), obviously inhibited the uptake of MCT in MDCK-hOCT1 cells and isolated rat primary hepatocytes, and attenuated the viability reduction and LDH release of the primary cultured rat hepatocytes caused by MCT. In conclusion, OCT1 mediates the hepatic uptake of MCT and may play an important role in MCT induced-hepatotoxicity. PMID:23831208

  13. Ruminal Prevotella spp. may play an important role in the conversion of plant lignans into human health beneficial antioxidants.

    PubMed

    Schogor, Ana L B; Huws, Sharon A; Santos, Geraldo T D; Scollan, Nigel D; Hauck, Barbara D; Winters, Ana L; Kim, Eun J; Petit, Hélène V

    2014-01-01

    Secoisolariciresinol diglucoside (SDG), the most abundant lignan in flaxseed, is metabolized by the ruminal microbiota into enterolignans, which are strong antioxidants. Enterolactone (EL), the main mammalian enterolignan produced in the rumen, is transferred into physiological fluids, with potentially human health benefits with respect to menopausal symptoms, hormone-dependent cancers, cardiovascular diseases, osteoporosis and diabetes. However, no information exists to our knowledge on bacterial taxa that play a role in converting plant lignans into EL in ruminants. In order to investigate this, eight rumen cannulated cows were used in a double 4 × 4 Latin square design and fed with four treatments: control with no flax meal (FM), or 5%, 10% and 15% FM (on a dry matter basis). Concentration of EL in the rumen increased linearly with increasing FM inclusion. Total rumen bacterial 16S rRNA concentration obtained using Q-PCR did not differ among treatments. PCR-T-RFLP based dendrograms revealed no global clustering based on diet indicating between animal variation. PCR-DGGE showed a clustering by diet effect within four cows that had similar basal ruminal microbiota. DNA extracted from bands present following feeding 15% FM and absent with no FM supplementation were sequenced and it showed that many genera, in particular Prevotella spp., contributed to the metabolism of lignans. A subsequent in vitro study using selected pure cultures of ruminal bacteria incubated with SDG indicated that 11 ruminal bacteria were able to convert SDG into secoisolariciresinol (SECO), with Prevotella spp. being the main converters. These data suggest that Prevotella spp. is one genus playing an important role in the conversion of plant lignans to human health beneficial antioxidants in the rumen. PMID:24709940

  14. The Role of Important Non-Parental Adults (VIPs) in the Lives of Older Adolescents: A Comparison of Three Ethnic Groups

    ERIC Educational Resources Information Center

    Haddad, Eileen; Chen, Chuansheng; Greenberger, Ellen

    2011-01-01

    Previous research has consistently documented the importance of VIPs (mentors or important non-parental adults) in the lives of adolescents. Little is known, however, about whether VIPs play the same important roles across ethnic groups and whether VIPs remain influential when adolescents are older and involved in romantic relationships. The…

  15. Role of additional PCBM layer between ZnO and photoactive layers in inverted bulk-heterojunction solar cells

    PubMed Central

    Cho, Shinuk; Kim, Kwang-Dae; Heo, Jinhee; Lee, Joo Yul; Cha, Gihoon; Seo, Bo Yeol; Kim, Young Dok; Kim, Yong Soo; Choi, Si-young; Lim, Dong Chan

    2014-01-01

    In order to induce greater light absorption, nano-patterning is often applied to the metal-oxide buffer layer in inverted bulk-heterojunction(BHJ) solar cells. However, current homogeneity was significantly disturbed at the interface, leading to an efficiency that was not fully optimized. In this work, an additional PC61BM layer was inserted between the ZnO ripple and the photoactive layer to enhance the electron extraction. The insertion of additional PC61BM layer provided substantial advantages in the operation of inverted BHJ solar cells; specifically, it enhanced current homogeneity and lowered accumulation and trapping of photogenerated charges at the ZnO interface. Inclusion of the additional PC61BM layer led to effective quenching of electron–hole recombination by a reduction in the number of accumulated charges at the surface of ZnO ripples. This resulted in a 16% increase in the efficiency of inverted BHJ solar cells to 7.7%, compared to solar cells without the additional PC61BM layer. PMID:24603531

  16. Re(de)fining the Orthographic Neighborhood: The Role of Addition and Deletion Neighbors in Lexical Decision and Reading

    ERIC Educational Resources Information Center

    Davis, Colin J.; Perea, Manuel; Acha, Joana

    2009-01-01

    The influence of addition and deletion neighbors on visual word identification was investigated in four experiments. Experiments 1 and 2 used Spanish stimuli. In Experiment 1, lexical decision latencies were slower and less accurate for words and nonwords with higher-frequency deletion neighbors (e.g., "jugar" in "juzgar"), relative to control…

  17. Role of the addition of cabergoline to the management of acromegalic patients resistant to longterm treatment with octreotide LAR.

    PubMed

    Vilar, Lucio; Azevedo, Monalisa F; Naves, Luciana Ansaneli; Casulari, Luiz Augusto; Albuquerque, José Luciano; Montenegro, Renan M; Montenegro, Renan M; Figueiredo, Patricia; Nascimento, Gilvan C; Faria, Manuel S

    2011-06-01

    The aim of this prospective open trial was to evaluate the efficacy in normalizing IGF-I levels of the addition of cabergoline to the treatment of acromegalic patients partially responsive to Octreotide-LAR (OCT-LAR), a long acting somatotastin analog (SSA). Fifty-two patients who did not achieve hormonal control after longterm therapy (at least, 12 months) with OCT-LAR (30 mg every 28 days intramuscularly) were given cabergoline in addition to the SSA treatment. Normalization of IGF-I levels was achieved in 40.4% of patients by 6 months after the addition of cabergoline (1.0-3.0 mg/week; mean, 2.19 ± 0.64), and these patients were considered responsive. Compared to non-responsive subjects, responsive patients had significantly lower mean %ULNR-IGF-I and GH levels. However, the rate of hyperprolactinemia and positive immunohistochemical staining for PRL was similar in both groups, before the addition of cabergoline. Responsive patients were followed for at least 12 months on combination treatment and persisted with normal IGF-I levels. Patients with baseline %ULNR IGF-I up to 220% and/or GH up to 5 ng/ml were those who benefited the most from combination treatment. No patients with %ULNR-IGF-I>250% reached normalization of IGF-I levels. Our findings demonstrated that the addition of cabergoline, even at relatively low doses, is effective in both short- and long-term control of IGF-I levels in acromegalic patients partially responsive to octreotide LAR, particularly in those with mild/moderately elevated GH/IGF-levels, irrespective of prolactin status. PMID:21104199

  18. Geography Plays a More Important Role than Soil Composition on Structuring Genetic Variation of Pseudometallophyte Commelina communis

    PubMed Central

    Li, Jiaokun; Xu, Hui; Song, Yunpeng; Tang, Lulu; Gong, Yanbing; Yu, Runlan; Shen, Li; Wu, Xueling; Liu, Yuandong; Zeng, Weimin

    2016-01-01

    Pseudometallophytes are excellent models to study microevolution and local adaptation to soil pollution, as they can grow both on metalliferous and contrasting non-metalliferous soils. Although, there has been accumulating evidence for the effects of edaphic conditions and geographical isolation on the genetic structure of pesudometallophytes, it is still a difficult problem in evolutionary biology to assess their relative importance. In this study, we investigated the spatial patterns of genetic variability, population differentiation and genetic groups in pseudometallophyte Commelina communis with 12 microsatellite loci. Eight metallicolous and six non-metallicolous populations of C. communis were sampled from cupriferous sites and surrounding non-contaminated areas in China. Neither significant reduction in genetic diversity nor apparent founder and bottleneck effects were observed in metallicolous populations of C. communis. Based on Bayesian and Neighbor-Joining clustering analyses and a principal coordinates analysis, all sampled populations were found to be mainly separated into three genetic groups, corresponding well to their geographical locations rather than edaphic origins. Moreover, a significant and strong correlation between population genetic divergence and geographical distance were detected by Mantel test (r = 0.33; P < 0.05) and multiple matrix regression with randomization (MMRR; βD = 0.57, P < 0.01). However, the effect of copper concentration on genetic patterns of C. communis was not significant (MMRR; βE = -0.17, P = 0.12). Our study clearly demonstrated that the extreme edaphic conditions in metalliferous areas had limited effects on the genetic variability in C. communis. Geographic distance played a more important role in affecting the genetic structure of C. communis than soil composition did. In C. communis, the geographically disjunctive populations on metalliferous soils had multiple origins and evolved independently from nearby non

  19. Campylobacter jejuni Outer Membrane Vesicles Play an Important Role in Bacterial Interactions with Human Intestinal Epithelial Cells

    PubMed Central

    Elmi, Abdi; Watson, Eleanor; Sandu, Pamela; Gundogdu, Ozan; Mills, Dominic C.; Inglis, Neil F.; Manson, Erin; Imrie, Lisa; Bajaj-Elliott, Mona; Wren, Brendan W.; Smith, David G. E.

    2012-01-01

    Campylobacter jejuni is the most prevalent cause of food-borne gastroenteritis in the developed world; however, the molecular basis of pathogenesis is unclear. Secretion of virulence factors is a key mechanism by which enteric bacterial pathogens interact with host cells to enhance survival and/or damage the host. However, C. jejuni lacks the virulence-associated secretion systems possessed by other enteric pathogens. Many bacterial pathogens utilize outer membrane vesicles (OMVs) for delivery of virulence factors into host cells. In the absence of prototypical virulence-associated secretion systems, OMVs could be an important alternative for the coordinated delivery of C. jejuni proteins into host cells. Proteomic analysis of C. jejuni 11168H OMVs identified 151 proteins, including periplasmic and outer membrane-associated proteins, but also many determinants known to be important in survival and pathogenesis, including the cytolethal distending toxin (CDT). C. jejuni OMVs contained 16 N-linked glycoproteins, indicating a delivery mechanism by which these periplasm-located yet immunogenic glycoproteins can interact with host cells. C. jejuni OMVs possess cytotoxic activity and induce a host immune response from T84 intestinal epithelial cells (IECs), which was not reduced by OMV pretreatment with proteinase K or polymyxin B prior to coincubation with IECs. Pretreatment of IECs with methyl-beta-cyclodextrin partially blocks OMV-induced host immune responses, indicating a role for lipid rafts in host cell plasma membranes during interactions with C. jejuni OMVs. OMVs isolated from a C. jejuni 11168H cdtA mutant induced interleukin-8 (IL-8) to the same extent as did wild-type OMVs, suggesting OMV induction of IL-8 is independent of CDT. PMID:22966047

  20. Biological Roles of the Podospora anserina Mitochondrial Lon Protease and the Importance of Its N-Domain

    PubMed Central

    Adam, Céline; Picard, Marguerite; Déquard-Chablat, Michelle; Sellem, Carole H.; Denmat, Sylvie Hermann-Le; Contamine, Véronique

    2012-01-01

    Mitochondria have their own ATP-dependent proteases that maintain the functional state of the organelle. All multicellular eukaryotes, including filamentous fungi, possess the same set of mitochondrial proteases, unlike in unicellular yeasts, where ClpXP, one of the two matricial proteases, is absent. Despite the presence of ClpXP in the filamentous fungus Podospora anserina, deletion of the gene encoding the other matricial protease, PaLon1, leads to lethality at high and low temperatures, indicating that PaLON1 plays a main role in protein quality control. Under normal physiological conditions, the PaLon1 deletion is viable but decreases life span. PaLon1 deletion also leads to defects in two steps during development, ascospore germination and sexual reproduction, which suggests that PaLON1 ensures important regulatory functions during fungal development. Mitochondrial Lon proteases are composed of a central ATPase domain flanked by a large non-catalytic N-domain and a C-terminal protease domain. We found that three mutations in the N-domain of PaLON1 affected fungal life cycle, PaLON1 protein expression and mitochondrial proteolytic activity, which reveals the functional importance of the N-domain of the mitochondrial Lon protease. All PaLon1 mutations affected the C-terminal part of the N-domain. Considering that the C-terminal part is predicted to have an α helical arrangement in which the number, length and position of the helices are conserved with the solved structure of its bacterial homologs, we propose that this all-helical structure participates in Lon substrate interaction. PMID:22693589

  1. Geography Plays a More Important Role than Soil Composition on Structuring Genetic Variation of Pseudometallophyte Commelina communis.

    PubMed

    Li, Jiaokun; Xu, Hui; Song, Yunpeng; Tang, Lulu; Gong, Yanbing; Yu, Runlan; Shen, Li; Wu, Xueling; Liu, Yuandong; Zeng, Weimin

    2016-01-01

    Pseudometallophytes are excellent models to study microevolution and local adaptation to soil pollution, as they can grow both on metalliferous and contrasting non-metalliferous soils. Although, there has been accumulating evidence for the effects of edaphic conditions and geographical isolation on the genetic structure of pesudometallophytes, it is still a difficult problem in evolutionary biology to assess their relative importance. In this study, we investigated the spatial patterns of genetic variability, population differentiation and genetic groups in pseudometallophyte Commelina communis with 12 microsatellite loci. Eight metallicolous and six non-metallicolous populations of C. communis were sampled from cupriferous sites and surrounding non-contaminated areas in China. Neither significant reduction in genetic diversity nor apparent founder and bottleneck effects were observed in metallicolous populations of C. communis. Based on Bayesian and Neighbor-Joining clustering analyses and a principal coordinates analysis, all sampled populations were found to be mainly separated into three genetic groups, corresponding well to their geographical locations rather than edaphic origins. Moreover, a significant and strong correlation between population genetic divergence and geographical distance were detected by Mantel test (r = 0.33; P < 0.05) and multiple matrix regression with randomization (MMRR; βD = 0.57, P < 0.01). However, the effect of copper concentration on genetic patterns of C. communis was not significant (MMRR; βE = -0.17, P = 0.12). Our study clearly demonstrated that the extreme edaphic conditions in metalliferous areas had limited effects on the genetic variability in C. communis. Geographic distance played a more important role in affecting the genetic structure of C. communis than soil composition did. In C. communis, the geographically disjunctive populations on metalliferous soils had multiple origins and evolved independently from nearby non

  2. Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

    PubMed

    Kimura, Louise F; Prezotto-Neto, José Pedro; Távora, Bianca C L F; Faquim-Mauro, Eliana L; Pereira, Nicole A; Antoniazzi, Marta M; Jared, Simone G S; Teixeira, Catarina F P; Santoro, Marcelo L; Barbaro, Katia C

    2015-09-01

    This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays. PMID:26100666

  3. ENU-induced Mutation in the DNA-binding Domain of KLF3 Reveals Important Roles for KLF3 in Cardiovascular Development and Function in Mice

    PubMed Central

    Kelsey, Lois; Flenniken, Ann M.; Qu, Dawei; Funnell, Alister P. W.; Pearson, Richard; Zhou, Yu-Qing; Voronina, Irina; Berberovic, Zorana; Wood, Geoffrey; Newbigging, Susan; Weiss, Edward S.; Wong, Michael; Quach, Ivan; Yeh, S. Y. Sandy; Deshwar, Ashish R.; Scott, Ian C.; McKerlie, Colin; Henkelman, Mark; Backx, Peter; Simpson, Jeremy; Osborne, Lucy; Rossant, Janet; Crossley, Merlin; Bruneau, Benoit; Adamson, S. Lee

    2013-01-01

    KLF3 is a Krüppel family zinc finger transcription factor with widespread tissue expression and no previously known role in heart development. In a screen for dominant mutations affecting cardiovascular function in N-ethyl-N-nitrosourea (ENU) mutagenized mice, we identified a missense mutation in the Klf3 gene that caused aortic valvular stenosis and partially penetrant perinatal lethality in heterozygotes. All homozygotes died as embryos. In the first of three zinc fingers, a point mutation changed a highly conserved histidine at amino acid 275 to arginine (Klf3H275R). This change impaired binding of the mutant protein to KLF3's canonical DNA binding sequence. Heterozygous Klf3H275R mutants that died as neonates had marked biventricular cardiac hypertrophy with diminished cardiac chambers. Adult survivors exhibited hypotension, cardiac hypertrophy with enlarged cardiac chambers, and aortic valvular stenosis. A dominant negative effect on protein function was inferred by the similarity in phenotype between heterozygous Klf3H275R mutants and homozygous Klf3 null mice. However, the existence of divergent traits suggested the involvement of additional interactions. We conclude that KLF3 plays diverse and important roles in cardiovascular development and function in mice, and that amino acid 275 is critical for normal KLF3 protein function. Future exploration of the KLF3 pathway provides a new avenue for investigating causative factors contributing to cardiovascular disorders in humans. PMID:23874215

  4. Suppressor of cytokine signaling 3 plays an important role in porcine circovirus type 2 subclinical infection by downregulating proinflammatory responses.

    PubMed

    Zhu, Xuejiao; Bai, Juan; Liu, Panrao; Wang, Xianwei; Jiang, Ping

    2016-01-01

    Porcine circovirus type 2 (PCV2) causes porcine circovirus-associated diseases and usually evokes a subclinical infection, without any obvious symptoms, in pigs. It remains unclear how PCV2 leads to a subclinical infection. In this study, we found that peripheral blood mononuclear cells (PBMCs) from PCV2-challenged piglets with no significant clinical symptoms exhibited increased expression of suppressor of cytokine signaling (SOCS) 3, but no significant changes in the expression of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α; this differed from piglets that displayed significant clinical symptoms. IL-6- and TNF-α-mediated signalings were inhibited in PBMCs from subclinical piglets. Elevated SOCS3 levels inhibited IL-6- and TNF-α-mediated NF-kappa-B inhibitor alpha degradation in PBMCs and PK-15 cells. SOCS3 production was also increased in PCV2-infected PK-15 porcine kidney cells, and IL-6 and TNF-α production that was induced by PCV2 in PK-15 cells was significantly increased when SOCS3 was silenced by a small interfering RNA. SOCS3 interacted with signal transducer and activator of transcription 3 and TNF-associated receptor-associated factor 2, suggesting mechanisms by which SOCS3 inhibits IL-6 and TNF-α signaling. We conclude that SOCS3 plays an important role in PCV2 subclinical infection by suppressing inflammatory responses in primary immune cells. PMID:27581515

  5. Methylome analysis reveals an important role for epigenetic changes in the regulation of the Arabidopsis response to phosphate starvation.

    PubMed

    Yong-Villalobos, Lenin; González-Morales, Sandra Isabel; Wrobel, Kazimierz; Gutiérrez-Alanis, Dolores; Cervantes-Peréz, Sergio Alan; Hayano-Kanashiro, Corina; Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Martínez, Octavio; Herrera-Estrella, Luis

    2015-12-29

    Phosphate (Pi) availability is a significant limiting factor for plant growth and productivity in both natural and agricultural systems. To cope with such limiting conditions, plants have evolved a myriad of developmental and biochemical strategies to enhance the efficiency of Pi acquisition and assimilation to avoid nutrient starvation. In the past decade, these responses have been studied in detail at the level of gene expression; however, the possible epigenetic components modulating plant Pi starvation responses have not been thoroughly investigated. Here, we report that an extensive remodeling of global DNA methylation occurs in Arabidopsis plants exposed to low Pi availability, and in many instances, this effect is related to changes in gene expression. Modifications in methylation patterns within genic regions were often associated with transcriptional activation or repression, revealing the important role of dynamic methylation changes in modulating the expression of genes in response to Pi starvation. Moreover, Arabidopsis mutants affected in DNA methylation showed that changes in DNA methylation patterns are required for the accurate regulation of a number of Pi-starvation-responsive genes and that DNA methylation is necessary to establish proper morphological and physiological phosphate starvation responses. PMID:26668375

  6. Methylome analysis reveals an important role for epigenetic changes in the regulation of the Arabidopsis response to phosphate starvation

    PubMed Central

    Yong-Villalobos, Lenin; González-Morales, Sandra Isabel; Wrobel, Kazimierz; Gutiérrez-Alanis, Dolores; Cervantes-Peréz, Sergio Alan; Hayano-Kanashiro, Corina; Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Martínez, Octavio; Herrera-Estrella, Luis

    2015-01-01

    Phosphate (Pi) availability is a significant limiting factor for plant growth and productivity in both natural and agricultural systems. To cope with such limiting conditions, plants have evolved a myriad of developmental and biochemical strategies to enhance the efficiency of Pi acquisition and assimilation to avoid nutrient starvation. In the past decade, these responses have been studied in detail at the level of gene expression; however, the possible epigenetic components modulating plant Pi starvation responses have not been thoroughly investigated. Here, we report that an extensive remodeling of global DNA methylation occurs in Arabidopsis plants exposed to low Pi availability, and in many instances, this effect is related to changes in gene expression. Modifications in methylation patterns within genic regions were often associated with transcriptional activation or repression, revealing the important role of dynamic methylation changes in modulating the expression of genes in response to Pi starvation. Moreover, Arabidopsis mutants affected in DNA methylation showed that changes in DNA methylation patterns are required for the accurate regulation of a number of Pi-starvation–responsive genes and that DNA methylation is necessary to establish proper morphological and physiological phosphate starvation responses. PMID:26668375

  7. Role of dimerization in yeast aspartyl-tRNA synthetase and importance of the class II invariant proline.

    PubMed Central

    Eriani, G; Cavarelli, J; Martin, F; Dirheimer, G; Moras, D; Gangloff, J

    1993-01-01

    Cytoplasmic aspartyl-tRNA synthetase (AspRS; EC 6.1.1.12) from yeast is, as are most class II synthetases, an alpha 2 dimer. The only invariant amino acid in signature motif 1 of this class is Pro-273; this residue is located at the dimer interface. To understand the role of Pro-273 in the conserved dimeric configuration, we tested the effect of a Pro-273-->Gly (P273G) substitution on the catalytic properties of homo- and heterodimeric AspRS. Heterodimers of AspRS were produced in vivo by overexpression of their respective subunit variants from plasmid-encoded genes and purified to homogeneity in one HPLC step. The homodimer containing the P273G shows an 80% inactivation of the enzyme and an affinity decrease for its cognate tRNA(Asp) of one order of magnitude. The P273G-mutated subunit recovered wild-type enzymatic properties when associated with a native subunit or a monomer otherwise inactivated having an intact dimeric interface domain. These results, which can be explained by the crystal structure of the native enzyme complexed with its substrates, confirm the structural importance of Pro-273 for dimerization and clearly establish the functional interdependence of the AspRS subunits. More generally, the dimeric conformation may be a structural prerequisite for the activity of mononucleotide binding sites constructed from antiparallel beta strands. Images Fig. 1 Fig. 3 PMID:8248175

  8. Does arsenic play an important role in the soil microbial community around a typical arsenic mining area?

    PubMed

    Wu, Fan; Wang, Jun-Tao; Yang, Jun; Li, Jing; Zheng, Yuan-Ming

    2016-06-01

    Arsenic (As) can cause serious hazards to human health, especially in mining areas. Soil bacterial communities, which are critical parts of the soil ecosystem, were analyzed directly for soil environmental factors. As a consequence, it is of great significance to understand the ecological risk of arsenic contamination on bacteria, especially at the local scale. In this study, 33 pairs of soil and grain samples were collected from the corn and paddy fields around an arsenic mining area in Shimen County in Hunan Province, China. Significant differences were found between the soil nitrogen, As concentrations, and bacteria activities among these two types of land use. According to the structural equation model (SEM) analysis, compared with other environmental factors, soil As was not the key factor affecting the bacterial community, even when grain As was beyond the threshold of the national food hygiene standards of China. In the corn field, soil pH was the main factor dominating the bacterial richness, composition and grain As. Meanwhile, in the paddy field the soil total nitrogen (TN) and total carbon (TC) were the main factors impacting the bacterial richness, and the bacterial community composition was mainly affected by pH. The interactions between grain As and soil As were weak in the corn field. The bacterial communities played important roles in the food chain risk of As. The local policy of transforming paddy soil to dry land could greatly reduce the health risk of As through the food chain. PMID:27055093

  9. Physiological analyses indicate superoxide dismutase, catalase, and phytochelatins play important roles in Pb tolerance in Eremochloa ophiuroides.

    PubMed

    Li, Xi; Cen, Huameng; Chen, Youxiang; Xu, Siying; Peng, Lingli; Zhu, Hanmingyue; Li, Yiqiao

    2016-01-01

    Phytoremediation is considered to be a promising approach to restore or stabilize soil contaminated by lead (Pb). Turfgrasses, due to their high biomass yields, are considered to be suitable for use in phytoextraction of soil contaminated with heavy metal. It has been demonstrated that centipedegrass (Eremochloa ophiuroides (Munro) Hack., Poaceae) is a good turfgrass for restore of soil contaminated by Pb. However, the enhanced tolerant mechanisms in metallicolous (M) centipedegrass accessions remain unknown. In this study, we made a comparative study of growth performance, Pb accumulation, antioxidant levels, and phytochelatin concentrations in roots and shoots from M and nonmetallicolous (NM) centipedegrass accessions. Results showed that turf quality and growth rate were less repressed in M accessions than in NM accession. Pb stress caused generation of reactive oxygen species in centipedegrass with relatively lower levels in M accessions. Antioxidant activity analysis indicated that superoxide dismutase and catalase played important roles in Pb tolerance in M accessions. M accessions accumulated more Pb in roots and shoots. Greatly increased phytochelatins and less repressed sulfur contents in roots and shoots of M accessions indicated that they correlated with Pb accumulation and tolerance in centipedegrass. PMID:26368658

  10. Suppressor of cytokine signaling 3 plays an important role in porcine circovirus type 2 subclinical infection by downregulating proinflammatory responses

    PubMed Central

    Zhu, Xuejiao; Bai, Juan; Liu, Panrao; Wang, Xianwei; Jiang, Ping

    2016-01-01

    Porcine circovirus type 2 (PCV2) causes porcine circovirus-associated diseases and usually evokes a subclinical infection, without any obvious symptoms, in pigs. It remains unclear how PCV2 leads to a subclinical infection. In this study, we found that peripheral blood mononuclear cells (PBMCs) from PCV2-challenged piglets with no significant clinical symptoms exhibited increased expression of suppressor of cytokine signaling (SOCS) 3, but no significant changes in the expression of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α; this differed from piglets that displayed significant clinical symptoms. IL-6- and TNF-α-mediated signalings were inhibited in PBMCs from subclinical piglets. Elevated SOCS3 levels inhibited IL-6- and TNF-α-mediated NF-kappa-B inhibitor alpha degradation in PBMCs and PK-15 cells. SOCS3 production was also increased in PCV2-infected PK-15 porcine kidney cells, and IL-6 and TNF-α production that was induced by PCV2 in PK-15 cells was significantly increased when SOCS3 was silenced by a small interfering RNA. SOCS3 interacted with signal transducer and activator of transcription 3 and TNF-associated receptor-associated factor 2, suggesting mechanisms by which SOCS3 inhibits IL-6 and TNF-α signaling. We conclude that SOCS3 plays an important role in PCV2 subclinical infection by suppressing inflammatory responses in primary immune cells. PMID:27581515

  11. HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse

    PubMed Central

    Ichiyanagi, Tomoko; Ichiyanagi, Kenji; Ogawa, Ayako; Kuramochi-Miyagawa, Satomi; Nakano, Toru; Chuma, Shinichiro; Sasaki, Hiroyuki; Udono, Heiichiro

    2014-01-01

    HSP90, found in all kingdoms of life, is a major chaperone protein regulating many client proteins. We demonstrated that HSP90α, one of two paralogs duplicated in vertebrates, plays an important role in the biogenesis of fetal PIWI-interacting RNAs (piRNA), which act against the transposon activities, in mouse male germ cells. The knockout mutation of Hsp90α resulted in a large reduction in the expression of primary and secondary piRNAs and mislocalization of MIWI2, a PIWI homolog. Whereas the mutation in Fkbp6 encoding a co-chaperone reduced piRNAs of 28–32 nucleotides in length, the Hsp90α mutation reduced piRNAs of 24–32 nucleotides, suggesting the presence of both FKBP6-dependent and -independent actions of HSP90α. Although DNA methylation and mRNA levels of L1 retrotransposon were largely unchanged in the Hsp90α mutant testes, the L1-encoded protein was increased, suggesting the presence of post-transcriptional regulation. This study revealed the specialized function of the HSP90α isofom in the piRNA biogenesis and repression of retrotransposons during the development of male germ cells in mammals. PMID:25262350

  12. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection.

    PubMed

    Li, Qingxue; Wilkie, Adrian R; Weller, Melodie; Liu, Xueqiao; Cohen, Jeffrey I

    2015-07-01

    Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with αVβ3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in

  13. THY-1 Cell Surface Antigen (CD90) Has an Important Role in the Initial Stage of Human Cytomegalovirus Infection

    PubMed Central

    Li, Qingxue; Wilkie, Adrian R.; Weller, Melodie; Liu, Xueqiao; Cohen, Jeffrey I.

    2015-01-01

    Human cytomegalovirus (HCMV) infects about 50% of the US population, is the leading infectious cause of birth defects, and is considered the most important infectious agent in transplant recipients. The virus infects many cell types in vivo and in vitro. While previous studies have identified several cellular proteins that may function at early steps of infection in a cell type dependent manner, the mechanism of virus entry is still poorly understood. Using a computational biology approach, correlating gene expression with virus infectivity in 54 cell lines, we identified THY-1 as a putative host determinant for HCMV infection in these cells. With a series of loss-of-function, gain-of-function and protein-protein interaction analyses, we found that THY-1 mediates HCMV infection at the entry step and is important for infection that occurs at a low m.o.i. THY-1 antibody that bound to the cell surface blocked HCMV during the initial 60 minutes of infection in a dose-dependent manner. Down-regulation of THY-1 with siRNA impaired infectivity occurred during the initial 60 minutes of inoculation. Both THY-1 antibody and siRNA inhibited HCMV-induced activation of the PI3-K/Akt pathway required for entry. Soluble THY-1 protein blocked HCMV infection during, but not after, virus internalization. Expression of exogenous THY-1 enhanced entry in cells expressing low levels of the protein. THY-1 interacted with HCMV gB and gH and may form a complex important for entry. However, since gB and gH have previously been shown to interact, it is uncertain if THY-1 directly binds to both of these proteins. Prior observations that THY-1 (a) interacts with αVβ3 integrin and recruits paxillin (implicated in HCMV entry), (b) regulates leukocyte extravasation (critical for HCMV viremia), and (c) is expressed on many cells targeted for HCMV infection including epithelial and endothelial cells, fibroblast, and CD34+/CD38- stem cells, all support a role for THY-1 as an HCMV entry mediator in

  14. Crystal structure-based exploration of the important role of Arg106 in the RNA-binding domain of human coronavirus OC43 nucleocapsid protein

    PubMed Central

    Chen, I-Jung; Yuann, Jeu-Ming P.; Chang, Yu-Ming; Lin, Shing-Yen; Zhao, Jincun; Perlman, Stanley; Shen, Yo-Yu; Huang, Tai-Huang; Hou, Ming-Hon

    2013-01-01

    Human coronavirus OC43 (HCoV-OC43) is a causative agent of the common cold. The nucleocapsid (N) protein, which is a major structural protein of CoVs, binds to the viral RNA genome to form the virion core and results in the formation of the ribonucleoprotein (RNP) complex. We have solved the crystal structure of the N-terminal domain of HCoV-OC43 N protein (N-NTD) (residues 58 to 195) to a resolution of 2.0Å. The HCoV-OC43 N-NTD is a single domain protein composed of a five-stranded β-sheet core and a long extended loop, similar to that observed in the structures of N-NTDs from other coronaviruses. The positively charged loop of the HCoV-OC43 N-NTD contains a structurally well-conserved positively charged residue, R106. To assess the role of R106 in RNA binding, we undertook a series of site-directed mutagenesis experiments and docking simulations to characterize the interaction between R106 and RNA. The results show that R106 plays an important role in the interaction between the N protein and RNA. In addition, we showed that, in cells transfected with plasmids that encoded the mutant (R106A) N protein and infected with virus, the level of the matrix protein gene was decreased by 7-fold compared to cells that were transfected with the wild-type N protein. This finding suggests that R106, by enhancing binding of the N protein to viral RNA plays a critical role in the viral replication. The results also indicate that the strength of N protein/RNA interactions is critical for HCoV-OC43 replication. PMID:23501675

  15. The Role of Skin Care as an Integral Component in the Management of Acne Vulgaris: Part 1: The Importance of Cleanser and Moisturizer Ingredients, Design, and Product Selection

    PubMed Central

    Del Rosso, James Q.

    2013-01-01

    Acne vulgaris is a very common facial skin disorder accounting for approximately 10 percent of all visits to ambulatory dermatology practices across the United States annually. Over time, greater attention has been directed to the roles of multiple epidermal barrier functions in various dermatological disorders, especially the stratum corneum permeability barrier and antimicrobial barrier. As a result, it has become readily apparent that professional direction of skin care is very important in the overall management of acne vulgaris. This article discusses several reasons that support the importance of incorporating specified skin care recommendations and instructions into the overall management plan for acne vulgaris. In addition, the article reviews formulation characteristics and some of the scientific data on two commercially available products that are recommended for use as a skin care regimen in patients with acne-prone and acne-affected skin, a foam wash and a moisturizer with a sun protection factor 30 broad spectrum photoprotection rating. The rationale for inclusion of specific ingredients are discussed along with an overview of research results including use in patients with acne vulgaris. PMID:24765221

  16. The Stable Level of Glutamine synthetase 2 Plays an Important Role in Rice Growth and in Carbon-Nitrogen Metabolic Balance

    PubMed Central

    Bao, Aili; Zhao, Zhuqing; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei

    2015-01-01

    Glutamine synthetase 2 (GS2) is a key enzyme involved in the ammonium metabolism in plant leaves. In our previous study, we obtained GS2-cosuppressed plants, which displayed a normal growth phenotype at the seedling stage, while at the tillering stage they showed a chlorosis phenotype. In this study, to investigate the chlorosis mechanism, we systematically analyzed the plant growth, carbon-nitrogen metabolism and gene expressions between the GS2-cosuppressed rice and wild-type plants. The results revealed that the GS2-cosuppressed plants exhibited a poor plant growth phenotype and a poor nitrogen transport ability, which led to nitrogen accumulation and a decline in the carbon/nitrogen ratio in the stems. Interestingly, there was a higher concentration of soluble proteins and a lower concentration of carbohydrates in the GS2-cosuppressed plants at the seedling stage, while a contrasting result was displayed at the tillering stage. The analysis of the metabolic profile showed a significant increase of sugars and organic acids. Additionally, gene expression patterns were different in root and leaf of GS2-cosuppressed plants between the seedling and tillering stage. These results indicated the important role of a stable level of GS2 transcription during normal rice development and the importance of the carbon-nitrogen metabolic balance in rice growth. PMID:26053400

  17. Glucocorticoids play an important role in mediating the enhanced metabolism of arginine and glutamine in enterocytes of postweaning pigs.

    PubMed

    Flynn, N E; Wu, G

    1997-05-01

    Weaning is associated with increased intestinal metabolism of glutamine and arginine as well as elevated plasma concentrations of cortisol (the major circulating glucocorticoid) in pigs. The objective of this study was to determine if cortisol plays an important role in mediating the enhanced amino acid metabolism in enterocytes of weaned pigs by administering RU486 (a glucocorticoid receptor antagonist). Eighteen 21-d-old pigs were randomly assigned to three groups of six. Two of these groups received intramuscular injections of 0 or 10 mg RU486 per kg body weight 5 min before and 24 and 72 h after weaning to a corn-soybean meal-based diet. The third group was allowed to suckle freely from sows. When the pigs were 29 d old, jugular venous blood was obtained and pigs were killed for preparation of jejunal enterocytes. The activities of arginase, argininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and pyrroline-5-carboxylate (P5C) synthase were measured. For metabolic studies, cells were incubated for 0 or 30 min at 37 degrees C in 2 mL of Krebs-bicarbonate buffer (pH 7.4) containing 0 or 2 mmol/L L-[U-14C]arginine or 2 mmol/L L-[U-14C]glutamine. In comparison with suckling pigs, weaning resulted in increases in the following: 1) the activities of arginase, ASS, ASL and P5C synthase, 2) the metabolism of arginine to CO2, proline and ornithine, and 3) the conversion of glutamine to ornithine, citrulline and CO2. The effects of the administration of RU486 were as follows: 1) attenuation of the increase in arginase activity and the production of ornithine from arginine, 2) abolition of the induction of ASL and P5C synthase, and 3) prevention of the increase in glutamine metabolism and the production of proline and CO2 from arginine in enterocytes of weaned pigs. These data suggest that glucocorticoids play an essential role in mediating the enhanced intestinal degradation of arginine and glutamine during weaning. PMID:9164994

  18. Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges

    PubMed Central

    2013-01-01

    Background Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Discussion Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product´s safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to

  19. Autophagy plays an important role in Sunitinib-mediated cell death in H9c2 cardiac muscle cells

    SciTech Connect

    Zhao Yuqin; Xue Tao; Yang Xiaochun; Zhu Hong; Ding Xiaofei; Lou Liming; Lu Wei; Yang Bo; He Qiaojun

    2010-10-01

    Sunitinib, which is a multitargeted tyrosine-kinase inhibitor, exhibits antiangiogenic and antitumor activity, and extends survival of patients with metastatic renal-cell carcinoma (mRCC) and gastrointestinal stromal tumors (GIST). This molecule has also been reported to be associated with cardiotoxicity at a high frequency, but the mechanism is still unknown. In the present study, we observed that Sunitinib showed high anti-proliferative effect on H9c2 cardiac muscle cells measured by PI staining and the MTT assay. But apoptotic markers (PARP cleavage, caspase 3 cleavage and chromatin condensation) were uniformly negative in H9c2 cells after Sunitinib treatment for 48 h, indicating that another cell death pathway may be involved in Sunitinib-induced cardiotoxicity. Here we found Sunitinib dramatically increased autophagic flux in H9c2 cells. Acidic vesicle fluorescence and high expression of LC3-II in H9c2 cells identified autophagy as a Sunitinib-induced process that might be associated with cytotoxicity. Furthermore, knocking down Beclin 1 by RNA-interference to block autophagy in H9c2 cells revealed that the death rate was decreased when treated with Sunitinib in comparison to control cells. These results confirmed that autophagy plays an important role in Sunitinib-mediated H9c2 cells cytotoxicity. Taken together, the data presented here strongly suggest that autophagy is associated with Sunitinib-induced cardiotoxicity, and that inhibition of autophagy constitutes a viable strategy for reducing Sunitinib-induced cardiomyocyte death thereby alleviating Sunitinib cardiotoxicity.

  20. The importance of the pharmacist's expanding role on the diabetes team: reinforcing nutritional guidelines for improved glycemic control.

    PubMed

    Johnson, L C; Beach, E

    1997-10-01

    The role of the pharmacist on the diabetes care team is expanding due to the increasing number of patients diagnosed with diabetes, limited health care dollars, and the education related to and required for patients by managed care organizations and insurance companies. In the past, training of patients in diabetes self-management skills has been inadequate, and this continues to be the case. Clinical pharmacists, in cooperation with physicians, have increased opportunities to provide education about medications and may include instructions for patients regarding the interaction of food consumed with changes in blood glucose levels. Because of monthly refills on prescribed medications, a patient's interaction with the pharmacist in the setting of a commercial pharmacy is more frequent than with any other member of the diabetes team. This contact offers an ideal educational opportunity. The action and efficacy of medications that affect the pancreas, hepatic glucose production, the utilization of glucose by muscle cells, and the absorption of glucose from the intestines are influenced directly by the meal plan. Nutritional guidelines, meal planning for the Type I and Type II patient, use of the exchange system, carbohydrate counting, artificial sweeteners, alcoholic beverages, and suggestions for guiding patients to establish eating habits that lead to improved diabetes control are important issues for every member of the diabetes team to address. The reinforcement of dietary principles may occur in the educational setting of the hospital or the clinic or within the commercial pharmacy setting. When the team presents accurate and current information, continuity of care and improved patient understanding are achieved. PMID:10173309

  1. On the role of the interactions of ions with external magnetic fields in physiologic processes and their importance in chronobiology.

    PubMed

    Ulmer, W

    2002-01-01

    Homage to the scientific work of Franz Halberg is inevitably connected with the development and importance of chronobiology and its applications in chronomedicine. We show that nonlinear reaction-diffusion systems with feedsideward coupling give rise to oscillations between different limit cycles favoring either inhibition or stimulation of the growth or decay of a component. The inclusion of the diffusion part of each concentration distribution offers the possibility of also taking into account the interaction of charged constituents with external magnetic fields. Concentration oscillations between different limit cycles of the constituents can thus be stabilized. It is assumed that the z-component of the external magnetic field is related to the rather weak solar magnetic field (ca. 10(-9) Tesla). Periods of about one week result for some positive (Mg2+, Ca2+, K+) and negative (e.g. Cl-) ions and some organic acids containing phosphates. The resonance time of a free proton H+ determining the oscillations of the pH-value is about 1 day and that of OH1 is about 3.5 days (half a week). The influence of the geomagnetic field (x- or y-component) in the same range is of a few to ca. 20-30 minutes in the case of charged proteins. An essential condition for this separation is that in general the geomagnetic field does not coincide with the z-component of the solar magnetic field. As an example, the role of the timedependence of the growth and ATP-concentration of the irradiation of the tumor spheroid C3H-MA (mammary adenocarcinoma of mice) is presented. PMID:11980358

  2. Rac1 and Cdc42 Play Important Roles in Arsenic Neurotoxicity in Primary Cultured Rat Cerebellar Astrocytes.

    PubMed

    An, Yuan; Liu, Tingting; Liu, Xiaona; Zhao, Lijun; Wang, Jing

    2016-03-01

    This study aimed to explore whether Rac1 and Cdc42, representative members of Ras homologue guanosine triphosphatases (Rho GTPases), are involved in neurotoxicity induced by arsenic exposure in rat nervous system. Expressions of Rac1 and Cdc42 in rat cerebellum and cerebrum exposed to different doses of NaAsO2 (Wistar rats drank 0, 2, 10, and 50 mg/L NaAsO2 water for 3 months) were examined. Both Rac1 and Cdc42 expressions increased significantly in a dose-dependent manner in cerebellum (P < 0.01) by Western blot and immunohistochemistry assay, but in cerebrum, Rac1 and Cdc42 expressions only in 2 mg/L exposure groups were significantly higher than those in control groups (P < 0.01). Five to 50 μM NaAsO2 decreased cell viability in a dose-dependent manner in primary cultured rat astrocytes, whereas 1 μM NaAsO2 increased the cell viability in these cells. Rac1 inhibitor, NSC23766, decreased NaAsO2-induced apoptosis and increased the cell viability in primary cultured rat cerebellar astrocytes exposed to 30 μM NaAsO2. Cdc42 inhibitor, ZCL278, increased cell viability in the cells exposed to 30 μM NaAsO2. Taken together, our current studies in vivo and in vitro indicate that activations of Rac1 and Cdc42 play a very important role in arsenic neurotoxicity in rat cerebellum, providing a new insight into arsenic neurotoxicity. PMID:26231544

  3. Important role of PLC-γ1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells.

    PubMed

    Yadav, Vishal R; Song, Tengyao; Joseph, Leroy; Mei, Lin; Zheng, Yun-Min; Wang, Yong-Xiao

    2013-02-01

    An increase in intracellular calcium concentration ([Ca(2+)](i)) in pulmonary arterial smooth muscle cells (PASMCs) induces hypoxic cellular responses in the lungs; however, the underlying molecular mechanisms remain incompletely understood. We report, for the first time, that acute hypoxia significantly enhances phospholipase C (PLC) activity in mouse resistance pulmonary arteries (PAs), but not in mesenteric arteries. Western blot analysis and immunofluorescence staining reveal the expression of PLC-γ1 protein in PAs and PASMCs, respectively. The activity of PLC-γ1 is also augmented in PASMCs following hypoxia. Lentiviral shRNA-mediated gene knockdown of mitochondrial complex III Rieske iron-sulfur protein (RISP) to inhibit reactive oxygen species (ROS) production prevents hypoxia from increasing PLC-γ1 activity in PASMCs. Myxothiazol, a mitochondrial complex III inhibitor, reduces the hypoxic response as well. The PLC inhibitor U73122, but not its inactive analog U73433, attenuates the hypoxic vasoconstriction in PAs and hypoxic increase in [Ca(2+)](i) in PASMCs. PLC-γ1 knockdown suppresses its protein expression and the hypoxic increase in [Ca(2+)](i). Hypoxia remarkably increases inositol 1,4,5-trisphosphate (IP(3)) production, which is blocked by U73122. The IP(3) receptor (IP(3)R) antagonist 2-aminoethoxydiphenyl borate (2-APB) or xestospongin-C inhibits the hypoxic increase in [Ca(2+)](i). PLC-γ1 knockdown or U73122 reduces H(2)O(2)-induced increase in [Ca(2+)](i) in PASMCs and contraction in PAs. 2-APB and xestospongin-C produce similar inhibitory effects. In conclusion, our findings provide novel evidence that hypoxia activates PLC-γ1 by increasing RISP-dependent mitochondrial ROS production in the complex III, which causes IP(3) production, IP(3)R opening, and Ca(2+) release, playing an important role in hypoxic Ca(2+) and contractile responses in PASMCs. PMID:23204067

  4. Important Role of a Putative Lytic Transglycosylase Cj0843c in β-Lactam Resistance in Campylobacter jejuni

    PubMed Central

    Zeng, Ximin; Gillespie, Barbara; Lin, Jun

    2015-01-01

    Beta-lactam antibiotics are an important class of antibiotics for treating bacterial infections. Despite prevalent β-lactam resistance in Campylobacter jejuni, the leading bacterial cause of human diarrhea in developed countries, molecular mechanism of β-lactam resistance in C. jejuni is still largely unknown. In this study, C. jejuni 81–176 was used for random transposon mutagenesis. Screening of a 2,800-mutant library identified 22 mutants with increased susceptibility to ampicillin. Of these mutants, two mutants contains mutations in Cj0843c (a putative lytic transglycosylase gene) and in its upstream gene Cj0844c, respectively. Complementation experiment demonstrated that the Cj0843 contributes to β-lactam resistance. The Cj0843c insertional mutation was subsequently introduced to diverse C. jejuni clinical strains for MIC test, showing that Cj0843c contributes to both intrinsic and acquired β-lactam resistance of C. jejuni. Consistent with this finding, inactivation of Cj0843c also dramatically reduced β-lactamase activity. Genomic examination and PCR analysis showed Cj0843c is widely distributed in C. jejuni. High purity recombinant Cj0843c was produced for generation of specific antiserum. The Cj0843 was localized in the periplasm, as demonstrated by immunoblotting using specific antibodies. Turbidimetric assay further demonstrated the capability of the purified Cj0843c to hydrolyze cell walls. Inactivation of Cj0843c also significantly reduced C. jejuni colonization in the intestine. Together, this study identifies a mechanism of β-lactam resistance in C. jejuni and provides insights into the role of cell wall metabolism in regulating β-lactamase activity. PMID:26635760

  5. Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer.

    PubMed

    Mehdipour, Parvin; Mahdavi, Marzieh; Mohammadi-Asl, Javad; Atri, Morteza

    2011-09-01

    The involvement of ATM gene and specifically, the important role of D1853N polymorphism, as a three-hit hypothesis has been previously reported in an Iranian proband affected with brain tumor and this polymorphism could be screened in her relatives as well. The aim of present study was to investigate the involvement of D1853N polymorphism as a predisposition factor in 129 Iranian patients affected with primary breast cancer and 248 sex- and age-matched healthy controls. Mutant allele-specific PCR amplification (MASA) assay was performed to analyze the D1853N polymorphism in the ATM gene. The frequency of D1853N polymorphism in cases, internal and external controls was 31.0% (40/129), 26.9% (28/104) and 12.5% (18/144), respectively. The frequency of D1853N in total control groups, including normal external control and pedigree internal control, was 18.6% (46/248). The odds ratio was calculated with the logistic regression test, with an estimated relative risk of 2.579 (P=0.005). The significant difference was observed between the patient-carriers of this alteration and external controls (P=0.001). The number of controls harboring D1853N polymorphism was higher in internal control compared to external controls, and the difference was statistically significant (P=0.004). The significant difference was observed between the patient-carriers and external controls and could be considered as a predisposing and diagnostic marker in the population and specifically in the cancer-prone pedigrees. PMID:20396981

  6. Synthetic metallic dialkydithiocarbamates as antiwear and extreme-pressure additives for lubricating oils: Role of metal on their effectiveness

    SciTech Connect

    Tuli, D.K.; Sarin, R.; Gupta, A.K.

    1995-04-01

    Dialkydithiocarbamates of five metals have been synthesized in pure form by following a simple general method. The alkyl chain in each of these compounds has been kept the same so as to observe the performance variations due to metal ions. The EP properties expressed as load wear index and weld load indicated the highest performance by Bi followed by Pb, Sb, Zn and Mo. The antiwear properties in terms of wear scar diameter, relative anti-wear effectiveness and mean average wear scar diameter show a performance order of Bi > Pb > Sb > Zn > Mo. The large ionic radius metals (Bi, Pb & Sb) had the best overall load-carrying performance and their effectiveness increased substantially when the additive concentration was more than 0.004 gm atom/Kg. The results suggest that Bi has good potential to replace toxic Pb and Sb from existing lubrication systems. 18 refs., 7 refs., 1 tab.

  7. Plasmon excitation in metal slab by fast point charge: The role of additional boundary conditions in quantum hydrodynamic model

    SciTech Connect

    Zhang, Ying-Ying; An, Sheng-Bai; Song, Yuan-Hong Wang, You-Nian; Kang, Naijing; Mišković, Z. L.

    2014-10-15

    We study the wake effect in the induced potential and the stopping power due to plasmon excitation in a metal slab by a point charge moving inside the slab. Nonlocal effects in the response of the electron gas in the metal are described by a quantum hydrodynamic model, where the equation of electronic motion contains both a quantum pressure term and a gradient correction from the Bohm quantum potential, resulting in a fourth-order differential equation for the perturbed electron density. Thus, besides using the condition that the normal component of the electron velocity should vanish at the impenetrable boundary of the metal, a consistent inclusion of the gradient correction is shown to introduce two possibilities for an additional boundary condition for the perturbed electron density. We show that using two different sets of boundary conditions only gives rise to differences in the wake potential at large distances behind the charged particle. On the other hand, the gradient correction in the quantum hydrodynamic model is seen to cause a reduction in the depth of the potential well closest to the particle, and a reduction of its stopping power. Even for a particle moving in the center of the slab, we observe nonlocal effects in the induced potential and the stopping power due to reduction of the slab thickness, which arise from the gradient correction in the quantum hydrodynamic model.

  8. Role of Cu additive on the dielectric relaxation of Se75Te25 and Se85Te15 glassy alloys

    NASA Astrophysics Data System (ADS)

    Sharma, J.; Kumar, S.

    2010-07-01

    The effect of Cu additive on the dielectric relaxation of two binary Se-Te glassy systems, comparing the properties of a-Se75Te25, a-Se85Te15 and a-Se75Te15Cu10 alloys has been reported. The temperature and frequency dependence of dielectric parameters in Glassy Se75Te25, Se85Te15 and Se75Te15Cu10 alloys are studied by measuring capacitance and dissipation factor in the frequency range (1 kHz-5 MHz) and temperature range (300-350 K). A Debye like relaxation of dielectric behavior has been observed. A comprehensive study on the relaxation mechanism revealed that the presence of grains and grain boundaries across the pallet thickness is the basic relaxation process. A detailed analysis shows that the observed dielectric loss is in agreement with the Guintini's theory of dielectric dispersion based on two electron hopping over a potential barrier and is applicable in the present case. Dielectric constant (ɛ’), dielectric loss (ɛ”), loss tangent (δ) and capacitive reactance (Xc) are found highly frequency and temperature dependent. Dependence of these dielectric parameters over the metallic impurity Cu, has also been found in the present glassy system and has been discussed in terms of electronegativity difference between the elements used in making the aforesaid glassy system.

  9. Crystallization of the Membrane-Associated Annexin B1: Roles of Additive Screen, Dynamic Light Scattering, and Bioactivity Assay

    SciTech Connect

    Ding, F.; Xu, Y; Azzi, A; Zhu, D; Rehse, D; Chen, C; Sun, S; Lin, S

    2010-01-01

    Annexin B1 (AnxB1) is a calcium-dependent phospholipid binding protein from Taenia solium cysticercus and has been reported to possess anticoagulant activity, to inhibit phospholipase A{sub 2}, and to regulate membrane transport. Native AnxB1 and its selenomethionyl derivative have been overproduced in Escherichia coli and purified. The results of dynamic light scattering analysis showed that Hepes buffer combined with low concentration salts (NaCl or CaCl{sub 2}) was beneficial for preventing aggregation and for AnxB1 stabilization in the storage. After the additive screen, crystals have been yielded in the presence of guanidine hydrochloride (Gn-HCl). We determined that a low concentration of Gn-HCl significantly delayed clotting time and increased anticoagulant activity. Analysis of the crystal showed that in the presence of Gn-HCl, AnxB1 crystallizes in orthorhombic space group, which is modified from the cubic space group for crystals grown in the absence of Gn-HCl. A high quality data set (at 1.9 {angstrom}) has been collected successfully for crystals of L-selenomethionine labeled protein in the presence of Gn-HCl, to solve the structure with the single anomalous dispersion method (SAD). The unit cell parameters are a = 102.35 {angstrom}, b = 103.59 {angstrom}, c = 114.60 {angstrom}, {alpha} = {beta} = {gamma} = 90.00{sup o}.

  10. Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation

    PubMed Central

    Kim, Mee J.; Findlay, Gregory M.; Martin, Beth; Zhao, Jingjing; Bell, Robert J. A.; Smith, Robin P.; Ku, Angel A.; Shendure, Jay; Ahituv, Nadav

    2014-01-01

    In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (SORL1 exon 17, TRAF3IP2 exon 2, PPARG exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types. PMID:25340400

  11. Toll-Like Receptor 6 Plays an Important Role in Host Innate Resistance to Brucella abortus Infection in Mice

    PubMed Central

    de Almeida, Leonardo A.; Macedo, Gilson C.; Marinho, Fábio A. V.; Gomes, Marco T. R.; Corsetti, Patrícia P.; Silva, Aristóbolo M.; Cassataro, Juliana; Giambartolomei, Guillermo H.

    2013-01-01

    Brucella abortus is recognized by several Toll-like receptor (TLR)-associated pathways triggering proinflammatory responses that affect both the nature and intensity of the immune response. Previously, we demonstrated that B. abortus-mediated dendritic cell (DC) maturation and control of infection are dependent on the adaptor molecule MyD88. However, the involvement of all TLRs in response to B. abortus infection is not completely understood. Therefore, we decided to evaluate the requirement for TLR6 in host resistance to B. abortus. Here, we demonstrated that TLR6 is an important component for triggering an innate immune response against B. abortus. An in vitro luciferase assay indicated that TLR6 cooperates with TLR2 to sense Brucella and further activates NF-κB signaling. However, in vivo analysis showed that TLR6, not TLR2, is required for the efficient control of B. abortus infection. Additionally, B. abortus-infected dendritic cells require TLR6 to induce tumor necrosis factor alpha (TNF-α) and interleukin-12 (IL-12). Furthermore, our findings demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway is impaired in TLR2, TLR6, and TLR2/6 knockout (KO) DCs when infected with B. abortus, which may account for the lower proinflammatory cytokine production observed in TLR6 KO mouse dendritic cells. In summary, the results presented here indicate that TLR6 is required to trigger innate immune responses against B. abortus in vivo and is required for the full activation of DCs to induce robust proinflammatory cytokine production. PMID:23460520

  12. Transcriptional profiling of canola developing embryo and identification of the important roles of BnDof5.6 in embryo development and fatty acids synthesis.

    PubMed

    Deng, Wei; Yan, Fang; Zhang, Xiaolan; Tang, Yuwei; Yuan, Yujin

    2015-08-01

    Canola is an important vegetable oil crop globally, and the understanding of the molecular mechanism underlying fatty acids biosynthesis during seed embryo development is an important research goal. Here we report the transcriptional profiling analysis of developing canola embryos using RNA-sequencing (RNA-Seq) method. RNA-Seq analysis generated 58,579,451 sequence reads aligned with 32,243 genes. It was found that a total of 55 differential expression genes (DEGs) encoding 28 enzymes function in carbon flow to fatty acids of storage TAG. Most of the DEGs encoding above enzymes showed similar expression pattern, indicating the DEGs are cooperatively involved in carbon flow into fatty acids. In addition, 41 DEGs associated with signal transductions, transport and metabolic processing of auxin, gibberellin, abscisic acid, cytokinin and salicylic acids were found in the RNA-Seq database, which indicates the important roles of the phytohormones in controlling embryo development and fatty acids synthesis. 122 DEGs encoding transcriptional factor family members were found in developing canola embryos. Furthermore, BnDOF5.6, a zinc finger transcriptional factor gene, found in RNA-Seq database was down-regulated in developing canola embryos. The transgenic plants displayed reduced embryo sizes, decreased fatty acids contents and altered seed fatty acids composition in canola. Down-regulated of BnDof5.6 also changed the expression levels of genes involved in fatty acids synthesis and desaturation. Our results indicate that BnDof5.6 is required for embryo development and fatty acids synthesis in canola. Overall this study presents new information on the global expression patterns of genes during embryo development and will expand our understanding of the complex molecular mechanism of carbon flow into fatty acids and embryo development in canola. PMID:26092973

  13. The importance of having zinc during in vitro maturation of cattle cumulus-oocyte complex: role of cumulus cells.

    PubMed

    Anchordoquy, J M; Anchordoquy, J P; Sirini, M A; Picco, S J; Peral-García, P; Furnus, C C

    2014-10-01

    The aim of this study was to investigate the influence of zinc (Zn) on the health of cumulus-oocyte complex (COC) during in vitro maturation (IVM). Experiments were designed to evaluate the effect of Zn added to IVM medium on: DNA integrity, apoptosis, cumulus expansion and superoxide dismutase (SOD) activity of cumulus cells (CC). Also, role of CC on Zn transport during IVM was evaluated on oocyte developmental capacity. DNA damage and early apoptosis were higher in CC matured with 0 μg/ml Zn compared with 0.7, 1.1 and 1.5 μg/ml Zn (p < 0.05). Cumulus expansion did not show differences in COC matured with or without Zn supplementation (p > 0.05). Superoxide dismutase activity was higher in COC matured with 1.5 μg/ml Zn than with 0 μg/ml Zn (p < 0.05). Cleavage and blastocyst rates were recorded after IVM in three maturation systems: intact COCs, denuded oocytes with cumulus cells monolayer (DO + CC) and denuded oocytes (DO). Cleavage rates were similar when COC, DO + CC or DO were matured with 1.5 μg/ml Zn compared with control group (p > 0.05). Blastocyst rates were significantly higher in COC than in DO + CC and DO with the addition of 1.5 μg/ml Zn during IVM (p < 0.01). Blastocyst quality was enhanced in COC and DO + CC compared with DO when Zn was added to IVM medium (p < 0.001). The results of this study indicate that Zn supplementation to IVM medium (i) decreased DNA damage and apoptosis in CC; (ii) increased SOD activity in CC; (iii) did not modify cumulus expansion and cleavage rates after in vitro fertilization; (iv) improved subsequent embryo development up to blastocyst stage; and (v) enhanced blastocyst quality when CC were present either in intact COC or in coculture during IVM. PMID:25131826

  14. The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis.

    PubMed

    Chen, Han-Jou; Mitchell, Jacqueline C; Novoselov, Sergey; Miller, Jack; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline A; Cheetham, Michael E; Shaw, Christopher E

    2016-05-01

    Detergent-resistant, ubiquitinated and hyperphosphorylated Tar DNA binding protein 43 (TDP-43, encoded by TARDBP) neuronal cytoplasmic inclusions are the pathological hallmark in ∼95% of amyotrophic lateral sclerosis and ∼60% of frontotemporal lobar degeneration cases. We sought to explore the role for the heat shock response in the clearance of insoluble TDP-43 in a cellular model of disease and to validate our findings in transgenic mice and human amyotrophic lateral sclerosis tissues. The heat shock response is a stress-responsive protective mechanism regulated by the transcription factor heat shock factor 1 (HSF1), which increases the expression of chaperones that refold damaged misfolded proteins or facilitate their degradation. Here we show that manipulation of the heat shock response by expression of dominant active HSF1 results in a dramatic reduction of insoluble and hyperphosphorylated TDP-43 that enhances cell survival, whereas expression of dominant negative HSF1 leads to enhanced TDP-43 aggregation and hyperphosphorylation. To determine which chaperones were mediating TDP-43 clearance we over-expressed a range of heat shock proteins (HSPs) and identified DNAJB2a (encoded by DNAJB2, and also known as HSJ1a) as a potent anti-aggregation chaperone for TDP-43. DNAJB2a has a J domain, allowing it to interact with HSP70, and ubiquitin interacting motifs, which enable it to engage the degradation of its client proteins. Using functionally deleted DNAJB2a constructs we demonstrated that TDP-43 clearance was J domain-dependent and was not affected by ubiquitin interacting motif deletion or proteasome inhibition. This indicates that TDP-43 is maintained in a soluble state by DNAJB2a, leaving the total levels of TDP-43 unchanged. Additionally, we have demonstrated that the levels of HSF1 and heat shock proteins are significantly reduced in affected neuronal tissues from a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis and patients with

  15. The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis

    PubMed Central

    Chen, Han-Jou; Mitchell, Jacqueline C.; Novoselov, Sergey; Miller, Jack; Nishimura, Agnes L.; Scotter, Emma L.; Vance, Caroline A.; Cheetham, Michael E.

    2016-01-01

    Detergent-resistant, ubiquitinated and hyperphosphorylated Tar DNA binding protein 43 (TDP-43, encoded by TARDBP) neuronal cytoplasmic inclusions are the pathological hallmark in ∼95% of amyotrophic lateral sclerosis and ∼60% of frontotemporal lobar degeneration cases. We sought to explore the role for the heat shock response in the clearance of insoluble TDP-43 in a cellular model of disease and to validate our findings in transgenic mice and human amyotrophic lateral sclerosis tissues. The heat shock response is a stress-responsive protective mechanism regulated by the transcription factor heat shock factor 1 (HSF1), which increases the expression of chaperones that refold damaged misfolded proteins or facilitate their degradation. Here we show that manipulation of the heat shock response by expression of dominant active HSF1 results in a dramatic reduction of insoluble and hyperphosphorylated TDP-43 that enhances cell survival, whereas expression of dominant negative HSF1 leads to enhanced TDP-43 aggregation and hyperphosphorylation. To determine which chaperones were mediating TDP-43 clearance we over-expressed a range of heat shock proteins (HSPs) and identified DNAJB2a (encoded by DNAJB2, and also known as HSJ1a) as a potent anti-aggregation chaperone for TDP-43. DNAJB2a has a J domain, allowing it to interact with HSP70, and ubiquitin interacting motifs, which enable it to engage the degradation of its client proteins. Using functionally deleted DNAJB2a constructs we demonstrated that TDP-43 clearance was J domain-dependent and was not affected by ubiquitin interacting motif deletion or proteasome inhibition. This indicates that TDP-43 is maintained in a soluble state by DNAJB2a, leaving the total levels of TDP-43 unchanged. Additionally, we have demonstrated that the levels of HSF1 and heat shock proteins are significantly reduced in affected neuronal tissues from a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis and patients with

  16. Young Adults' Anticipated Identity Importance of Career, Marital, and Parental Roles: Comparisons of Men and Women with Different Role Balance Orientations.

    ERIC Educational Resources Information Center

    Kerpelman, Jennifer L.; Schvaneveldt, Paul L.

    1999-01-01

    Reports results from two studies, involving 1,267 and 147 college students that explored students' role-balance expectations for their future career, marital, and parental identities. Results from both studies provide evidence that contradicts previous assumptions about gender differences in expectations for work and family roles. (SLD)

  17. Additional Shear Resistance from Fault Roughness and its Role in Determining Stress Levels on Mature and Immature Faults

    NASA Astrophysics Data System (ADS)

    Fang, Z.; Dunham, E. M.

    2011-12-01

    The majority of crustal faults host earthquakes at τ /(σ - p) ˜ 0.6 (τ is shear stress and (σ - p) is the effective normal stress), while mature plate-boundary faults, like the San Andreas Fault (SAF), host earthquakes at τ /(σ - p) ˜ 0.2. A leading explaination for the weakness of the SAF is the existence of dynamic weakening, which, on planar faults, allows self-sustaining rupture at a critical background stress level τ pulse/(σ - p) ˜ 0.25. Provided that dynamic weakening also occurs on less mature faults, which seems likely given the ubiquity of dynamic weakening in high velocity friction experiments, the stress levels on the less mature faults are puzzling. We offer a self-consistent explanation for the relatively high stress levels on immature faults that is compatible with dynamic weakening and low coseismic strength of all faults. Our explanation is that increased geometrical complexity of less mature faults introduces an additional resistance to slip that must be overcome in order for the fault to host ruptures. Lab and field observations suggest that faults are self-similar surfaces with amplitude-to-wavelength ratio α in the range of 10-3 (mature faults) to 10-2 (immature faults). Slip on such faults induces huge stress perturbations near the fault. Projection of these stress perturbations back onto the rough fault surface results in an additional shear resistance to slip, the 'roughness drag' τ drag, that exists even if the fault is frictionless. A perturbation analysis, accurate to second order in α , shows that τ drag = 8π 3 α 2[G/(1-&nu)][Δ u/λ min], in which G is shear modulus, ν is the Poisson's ratio, Δ u is the amount of slip, and λ min is the minimum wavelength of roughness. Estimates indicate that τ drag is negligible on mature faults (α ˜ 10-3) but can become substantial on immature faults (α ˜ 10-2). We expect that the finite strength of the off-fault material ultimately bounds τ drag to a value determined by the

  18. Blinking fluorescence of single donor-acceptor pairs: Important role of ``dark'' states in resonance energy transfer via singlet levels

    NASA Astrophysics Data System (ADS)

    Osad'ko, I. S.; Shchukina, A. L.

    2012-06-01

    and A fluorescence trajectories with those measured by Weiss and co-workers proves the important role of triplet levels in energy transfer via singlet levels.

  19. Collagenase IV plays an important role in regulating hair cycle by inducing VEGF, IGF-1, and TGF-β expression

    PubMed Central

    Hou, Chun; Miao, Yong; Wang, Jin; Wang, Xue; Chen, Chao-Yue; Hu, Zhi-Qi

    2015-01-01

    , MMP-2 and MMP-9, play important roles in hair cycle, and this could be mediated by induced expression of VEGF, IGF-1, and TGF-β. PMID:26451090

  20. Down-regulation of carboxylesterases 1 and 2 plays an important role in prodrug metabolism in immunological liver injury rats.

    PubMed

    Zhang, Chengliang; Xu, Yanjiao; Gao, Ping; Lu, Jingli; Li, Xiping; Liu, Dong

    2015-02-01

    Liver plays a central role in xenobiotics metabolism, thus affecting the in vivo disposition and therapeutic effects of drugs. Carboxylesterases (CESs), with the main isoforms CES1 and CES2, are important in the metabolism of ester-type prodrugs. However, influences of immunological liver injury on the activity of CES remain undefined. In the present study, we demonstrated treatment with lipopolysaccharide (LPS) suppressed the activities of CES1 and CES2. The decreased activities of CES1 and CES2 were preliminarily assessed by the hydrolysis assay for their common substrate p-nitrophenyl acetate (PNPA) with rat hepatic microsomal enzyme. Subsequently, RT-PCR results showed that the levels of CES1 mRNA and mRNA of CES2 (AB010635) and CES2 (AY034877) in the model group were significantly lower than those of the normal control group (P<0.05). Western blot results showed that the expressions of CES1 and CES2 proteins were decreased (P<0.05). To further clarify the effects of LPS on the metabolic activities of CESs, pharmacokinetic studies were performed in rats by utilizing imidapril and irinotecan (CPT-11) as the specific substrates for CES1 and CES2, respectively. After treatment with LPS, AUC0-∞ and Cmax of imidaprilat were decreased from 2084.86±340.66ng·h(-1)·mL(-1) and 234.66±68.85ng·mL(-1) to 983.87±315.34ng·h(-1)·mL(-1) and 113.1±19.69ng·mL(-1) (P<0.05), respectively. Moreover, AUC0-∞ and Cmax of SN-38 were decreased from 8100±918.6ng·h(-1)·mL(-1) and 144.67±20.28ng·mL(-1) to 3270±500.5ng·h(-1)·mL(-1) and 56.19±10.38ng·mL(-1) (P<0.05), respectively. In summary, immunological liver injury remarkably attenuated the expressions and metabolic activities of CES1 and CES2, which may be associated with the regulatory effects of cytokines under inflammation. PMID:25499727

  1. Reader Response and Long-Term Recall for Journalistic Text: The Roles of Imagery, Affect, and Importance.

    ERIC Educational Resources Information Center

    Sadoski, Mark; Quast, Zeba

    1990-01-01

    Examines recall of three feature articles by rating paragraphs according to degree of mental imagery evoked, affect evoked, and importance of the article as a whole. Finds that readers are more likely to remember content that is subjectively important than content viewed as objectively important. (KEH)

  2. H2O2 plays an important role in the lifestyle of Colletotrichum gloeosporioides during interaction with cowpea [Vigna unguiculata (L.) Walp].

    PubMed

    Eloy, Ygor R G; Vasconcelos, Ilka M; Barreto, Ana L H; Freire-Filho, Francisco R; Oliveira, Jose T A

    2015-08-01

    Plant-fungus interactions usually generate H(2)O(2) in the infected plant tissue. H(2)O(2) has a direct antimicrobial effect and is involved in the cross-linking of cell walls, signaling, induction of gene expression, hypersensitive cell death and induced systemic acquired resistance. This has raised the hypothesis that H(2)O(2) manipulation by pharmacological compounds could alter the lifestyle of Colletotrichum gloeosporioides during interaction with the BR-3-Tracuateua cowpea genotype. The primary leaves of cowpea were excised, infiltrated with salicylic acid (SA), glucose oxidase + glucose (GO/G), catalase (CAT) or diphenyliodonium chloride (DPI), followed by spore inoculation on the adaxial leaf surface. SA or GO/G-treated plantlets showed increased H(2)O(2) accumulation and lipid peroxidation. The fungus used a subcuticular, intramural necrotrophic strategy, and developed secondary hyphae associated with the quick spread and rapid killing of host cells. However, CAT or DPI-treated leaves exhibited decreased H(2)O(2) concentration and lipid peroxidation and the fungus developed intracellular hemibiotrophic infection with vesicles, in addition to primary and secondary hyphal formation. These results suggest that H(2)O(2) plays an important role in the cowpea (C. gloeosporioides) pathosystem given that it affected fungal lifestyle during interaction. PMID:26228563

  3. How important is the role of crystal fractionation in making intermediate magmas? Insights from Zr and P systematics

    NASA Astrophysics Data System (ADS)

    Lee, Cin-Ty A.; Bachmann, Olivier

    2014-05-01

    Most magmatism on Earth forms by direct melting of the mantle, generating basalts at the low silica end of the terrestrial compositional spectrum. However, most subduction zone magmas erupted or sampled at the surface are basalt-andesitic to andesitic and hence have higher Si contents. Endmember hypotheses for the origin of andesites are: (1) direct melting of the mantle at water-saturated conditions, (2) partial re-melting of altered basaltic crust, (3) crystal fractionation of arc basalts in crustal magma chambers, and (4) mixing of mafic magmas with high Si crust or magmas, e.g., dacite-rhyolite. Here, we explore the possibility of using Zr and P systematics to evaluate the importance of some of these processes. Direct melting of the mantle generates magmas with low Zr (<50 ppm) and P2O5 (<0.2 wt.%). Crystal-liquid segregation should drive an increase in P and Zr in the residual magma because the magma is initially undersaturated in zircon and apatite. With further cooling and crystallization, apatite followed by zircon will saturate, causing P and Zr to decrease so that most rhyolites and granites will have low P and Zr (high temperature rhyolites may never saturate in zircon and will maintain high Zr contents). Mixing of basalts with rhyolites having low P and Zr should generate coupled decreases in Zr and P with increasing SiO2. Here, we show that Zr (>100 ppm) and P2O5 (>0.2 wt.%) in island- and continental-arc magmas initially increase to levels higher than what can be achieved if andesites form by direct mantle melting. As Si increases, both Zr and P decrease with Zr decreasing at higher Si, and hence lagging the decrease in P. These systematics, particularly the decoupled decrease in Zr and P, cannot be explained by mixing, and instead, are more easily explained if andesites are dominantly formed by crystal-liquid segregation from moderately hydrous basalt, wherein P and Zr are controlled, respectively, by early and later saturation in apatite and zircon

  4. Shugoshin1 May Play Important Roles in Separation of Homologous Chromosomes and Sister Chromatids during Mouse Oocyte Meiosis

    PubMed Central

    Yin, Shen; Ai, Jun-Shu; Shi, Li-Hong; Wei, Liang; Yuan, Ju; Ouyang, Ying-Chun; Hou, Yi; Chen, Da-Yuan; Schatten, Heide; Sun, Qing-Yuan

    2008-01-01

    Background Homologous chromosomes separate in meiosis I and sister chromatids separate in meiosis II, generating haploid gametes. To address the question why sister chromatids do not separate in meiosis I, we explored the roles of Shogoshin1 (Sgo1) in chromosome separation during oocyte meiosis. Methodology/Principal Findings Sgo1 function was evaluated by exogenous overexpression to enhance its roles and RNAi to suppress its roles during two meioses of mouse oocytes. Immunocytochemistry and chromosome spread were used to evaluate phenotypes. The exogenous Sgo1 overexpression kept homologous chromosomes and sister chromatids not to separate in meiosis I and meiosis II, respectively, while the Sgo1 RNAi promoted premature separation of sister chromatids. Conclusions Our results reveal that prevention of premature separation of sister chromatids in meiosis I requires the retention of centromeric Sgo1, while normal separation of sister chromatids in meiosis II requires loss of centromeric Sgo1. PMID:18949044

  5. S. 1082: This Act may be cited as the Hazardous and Additional Waste Export and Import Act of 1991, introduced in the US Senate, One Hundred Second Congress, First Session, May 15, 1991

    SciTech Connect

    Not Available

    1991-01-01

    This bill was introduced into the US Senate on May 15, 1991 to amend the Solid Waste Disposal Act. This legislation prohibits the export from and import into the United States of Hazardous and additional waste except in compliance with the requirements of this bill. The purpose of this act is to implement the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and Their Disposal, done at Basel, Switzerland, March 22, 1989. Key sections of this bill address the following: international shipments of hazardous and additional waste; objectives and national policy; retention of existing authority; and conforming amendments.

  6. When Are Teachers Motivated to Work beyond Retirement Age? The Importance of Support, Change of Work Role and Money

    ERIC Educational Resources Information Center

    Bal, P. Matthijs; Visser, Michel S.

    2011-01-01

    This article investigates the factors influencing the motivation to continue working after retirement among a sample of Dutch teachers. Based on previous research, it was proposed that teachers will be motivated to work after their legal retirement age when organizational support, possibilities to change work roles and financial needs are high.…

  7. U.S. Residency Directors' Views of the Importances of Seven Roles That Pediatrics Residents Should Master.

    ERIC Educational Resources Information Center

    Curry, Robert H.; And Others

    1991-01-01

    A survey of 129 pediatrics residency directors found strong agreement in support of 7 roles of the general and ambulatory-care pediatrician: ascertain and document health status and risk factors; perform intervention and technical procedures; communicate effectively; supervise patients and support personnel; demonstrate appropriate interpersonal…

  8. The important role of stellar atmosphere spectra for a consistent spectrophotometric calibration from the optical to the infrared wavelengths

    NASA Astrophysics Data System (ADS)

    Decin, L.

    2008-12-01

    We discuss the role of stellar atmosphere models in the spectrophotometric calibration pedigree. It is shown that stellar atmosphere spectra form an essential ingredient for spectrophotometric calibration. Compared with other (infrared) calibration networks currently available, the marcs grid is shown to provide the calibration community with spectral reference energy distributions of higher accuracy improving the spectrophotometric calibration of infrared spectrometers by more than 3%.

  9. NADPH Oxidase Dependent NLRP3 Inflammasome Activation Plays an Important Role in Lung Fibrosis by Multi-Walled Carbon Nanotubes

    PubMed Central

    Sun, Bingbing; Wang, Xiang; Ji, Zhaoxia; Wang, Meiying; Liao, Yu-Pei; Chang, Chong Hyun; Li, Ruibin; Zhang, Haiyuan; Nel, André E.; Xia, Tian

    2015-01-01

    The purpose of this communication is to elucidate the key role of NADPH oxidase in NLRP3 inflammasome activation and generation of pulmonary fibrosis by multi-walled carbon nanotubes (MWCNTs). Although it is known that oxidative stress plays a role in pulmonary fibrosis by single-walled CNTs, the role of specific sources of reactive oxygen species (ROS), including NADPH oxidase, in inflammasome activation remains to be clarified. In this study, three long aspect ratio (LAR) materials (MWCNTs, SWCNTs, and silver nanowires) are used to compare with spherical carbon black and silver nanoparticles for their ability to trigger oxygen burst activity and NLRP3 assembly. All LAR materials but not spherical nanoparticles induce robust NADPH oxidase activation and respiratory burst activity in THP-1 cells, which are blunted in p22phox deficient cells. NADPH oxidase is directly involved in lysosome damage by LAR materials, as demonstrated by decreased cathepsin B release and IL-1β production in p22phox deficient cells. Reduced respiratory burst activity and inflammasome activation are also observed in bone marrow-derived macrophages from p47phox deficient mice. Moreover, p47phox deficient mice have reduced IL-1β production and lung collagen deposition in response to MWCNTs. Lung fibrosis is also suppressed by N-acetyl-cysteine (NAC) in wild type animals exposed to MWCNTs. PMID:25581126

  10. The Role of Beliefs about the Importance of Social Skills in Elementary Children's Social Behaviors and School Attitudes

    ERIC Educational Resources Information Center

    Kwon, Kyongboon; Kim, Elizabeth Moorman; Sheridan, Susan M.

    2014-01-01

    Background: Positive attitudes toward school have been suggested as a meaningful indicator of school engagement among elementary children. The current study was guided by a social cognitive developmental perspective which suggests that social cognitions, including beliefs, play an important role in children's adjustment outcomes. Objective:…

  11. mTOR plays an important role in cow's milk allergy-associated behavioral and immunological deficits.

    PubMed

    Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; van der Horst, Hilma; Reinders, Margot T M; Broersen, Laus M; Willemsen, Linette E M; Kas, Martien J H; Garssen, Johan; Kraneveld, Aletta D

    2015-10-01

    Autism spectrum disorder (ASD) is multifactorial, with both genetic as well as environmental factors working in concert to develop the autistic phenotype. Immunological disturbances in autistic individuals have been reported and a role for food allergy has been suggested in ASD. Single gene mutations in mammalian target of rapamycin (mTOR) signaling pathway are associated with the development of ASD and enhanced mTOR signaling plays a central role in directing immune responses towards allergy as well. Therefore, the mTOR pathway may be a pivotal link between the immune disturbances and behavioral deficits observed in ASD. In this study it was investigated whether the mTOR pathway plays a role in food allergy-induced behavioral and immunological deficits. Mice were orally sensitized and challenged with whey protein. Meanwhile, cow's milk allergic (CMA) mice received daily treatment of rapamycin. The validity of the CMA model was confirmed by showing increased allergic immune responses. CMA mice showed reduced social interaction and increased repetitive self-grooming behavior. Enhanced mTORC1 activity was found in the brain and ileum of CMA mice. Inhibition of mTORC1 activity by rapamycin improved the behavioral and immunological deficits of CMA mice. This effect was associated with increase of Treg associated transcription factors in the ileum of CMA mice. These findings indicate that mTOR activation may be central to both the intestinal, immunological, and psychiatric ASD-like symptoms seen in CMA mice. It remains to be investigated whether mTOR can be seen as a therapeutic target in cow's milk allergic children suffering from ASD-like symptoms. PMID:26027949

  12. The Role of Social Support for Promoting Quality of Life among Persistently Obese Adolescents: Importance of Support in Schools

    ERIC Educational Resources Information Center

    Wu, Yelena P.; Reiter-Purtill, Jennifer; Zeller, Meg H.

    2014-01-01

    Background: Despite school-based and other interventions for pediatric obesity, many obese youth of the present generation will persist in their obesity into adolescence and adulthood. Thus, understanding not only how better to tailor weight interventions but how to promote overall adjustment for persistently obese youth is of utmost importance.…

  13. 2015 Survey of Board Professionals: Who They Are, What They Do, and Their Important Role in Governance

    ERIC Educational Resources Information Center

    Hodge-Clark, Kristen

    2015-01-01

    Board professionals provide critical support, planning, and coordination of important board functions. Their work is often unheralded and conducted behind the scenes, but it is critical to the success and performance of the board. Since 1991, the Association of Governing Boards (AGB) has surveyed this group to capture the changing nature of their…

  14. PHASER 2.10 methodology for dependence, importance, and sensitivity: The role of scale factors, confidence factors, and extremes

    SciTech Connect

    Cooper, J.A.

    1996-09-01

    PHASER (Probabilistic Hybrid Analytical System Evaluation Routine) is a software tool that has the capability of incorporating subjective expert judgment into probabilistic safety analysis (PSA) along with conventional data inputs. An earlier report described the PHASER methodology, but only gave a cursory explanation about how dependence was incorporated in Version 1.10 and about how ``Importance`` and ``Sensitivity`` measures were to be incorporated in Version 2.00. A more detailed description is given in this report. The basic concepts involve scale factors and confidence factors that are associated with the stochastic variability and subjective uncertainty (which are common adjuncts used in PSA), and the safety risk extremes that are crucial to safety assessment. These are all utilized to illustrate methodology for incorporating dependence among analysis variables in generating PSA results, and for Importance and Sensitivity measures associated with the results that help point out where any major sources of safety concern arise and where any major sources of uncertainty reside, respectively.

  15. Casuarina in Africa: distribution, role and importance of arbuscular mycorrhizal, ectomycorrhizal fungi and Frankia on plant development.

    PubMed

    Diagne, Nathalie; Diouf, Diegane; Svistoonoff, Sergio; Kane, Aboubacry; Noba, Kandioura; Franche, Claudine; Bogusz, Didier; Duponnois, Robin

    2013-10-15

    Exotic trees were introduced in Africa to rehabilitate degraded ecosystems. Introduced species included several Australian species belonging to the Casuarinaceae family. Casuarinas trees grow very fast and are resistant to drought and high salinity. They are particularly well adapted to poor and disturbed soils thanks to their capacity to establish symbiotic associations with mycorrhizal fungi -both arbuscular and ectomycorrhizal- and with the nitrogen-fixing bacteria Frankia. These trees are now widely distributed in more than 20 African countries. Casuarina are mainly used in forestation programs to rehabilitate degraded or polluted sites, to stabilise sand dunes and to provide fuelwood and charcoal and thus contribute considerably to improving livelihoods and local economies. In this paper, we describe the geographical distribution of Casuarina in Africa, their economic and ecological value and the role of the symbiotic interactions between Casuarina, mycorrhizal fungi and Frankia. PMID:23747371

  16. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets.

    PubMed

    Barbagallo, Davide; Condorelli, Angelo Giuseppe; Piro, Salvatore; Parrinello, Nunziatina; Fløyel, Tina; Ragusa, Marco; Rabuazzo, Agata Maria; Størling, Joachim; Purrello, Francesco; Di Pietro, Cinzia; Purrello, Michele

    2014-08-15

    Transcription factor CEBPA has been widely studied for its involvement in hematopoietic cell differentiation and causal role in hematological malignancies. We demonstrate here that it also performs a causal role in cytokine-induced apoptosis of pancreas β cells. Treatment of two mouse pancreatic α and β cell lines (αTC1-6 and βTC1) with proinflammatory cytokines IL-1β, IFN-γ, and TNF-α at doses that specifically induce apoptosis of βTC1 significantly increased the amount of mRNA and protein encoded by Cebpa and its proapoptotic targets, Arl6ip5 and Tnfrsf10b, in βTC1 but not in αTC1-6. Cebpa knockdown in βTC1 significantly decreased cytokine-induced apoptosis, together with the amount of Arl6ip5 and Tnfrsf10b. Analysis of the network comprising CEBPA, its targets, their first interactants, and proteins encoded by genes known to regulate cytokine-induced apoptosis in pancreatic β cells (genes from the apoptotic machinery and from MAPK and NFkB pathways) revealed that CEBPA, ARL6IP5, TNFRSF10B, TRAF2, and UBC are the top five central nodes. In silico analysis further suggests TRAF2 as trait d'union node between CEBPA and the NFkB pathway. Our results strongly suggest that Cebpa is a key regulator within the apoptotic network activated in pancreatic β cells during insulitis, and Arl6ip5, Tnfrsf10b, Traf2, and Ubc are key executioners of this program. PMID:24943845

  17. Activation of the AMPK-ULK1 pathway plays an important role in autophagy during prion infection

    PubMed Central

    Fan, Xue-Yu; Tian, Chan; Wang, Hui; Xu, Yin; Ren, Ke; Zhang, Bao-Yun; Gao, Chen; Shi, Qi; Meng, Ge; Zhang, Lu-Bin; Zhao, Yang-Jing; Shao, Qi-Xiang; Dong, Xiao-Ping

    2015-01-01

    AMPK is a serine/threonine protein kinase that acts as a positive regulator of autophagy, by phosphorylating ULK1 at specific sites. A previous study demonstrated activation of the macroautophagic system in scrapie-infected experimental rodents and in certain human prion diseases, in which the essential negative regulator mTOR is severely inhibited. In this study, AMPK and ULK1 in the brains of hamsters infected with scrapie strain 263 K and in the scrapie-infected cell line SMB-S15 were analysed. The results showed an up-regulated trend of AMPK and AMPK-Thr172, ULK1 and ULK1-Ser555. Increases in brain AMPK and ULK1 occurred at an early stage of agent 263 K infection. The level of phosphorylated ULK1-Ser757 decreased during mid-infection and was only negligibly present at the terminal stage, a pattern that suggested a close relationship of the phosphorylated protein with altered endogenous mTOR. In addition, the level of LKB1 associated with AMPK activation was selectively increased at the early and middle stages of infection. Knockdown of endogenous ULK1 in SMB-S15 cells inhibited LC3 lipidation. These results showed that, in addition to the abolishment of the mTOR regulatory pathway, activation of the AMPK-ULK1 pathway during prion infection contributes to autophagy activation in prion-infected brain tissues. PMID:26423766

  18. GCN2 kinase plays an important role triggering the remission phase of experimental autoimmune encephalomyelitis (EAE) in mice.

    PubMed

    Orsini, Heloisa; Araujo, Leandro P; Maricato, Juliana T; Guereschi, Marcia G; Mariano, Mario; Castilho, Beatriz A; Basso, Alexandre S

    2014-03-01

    Experimental autoimmune encephalomyelitis (EAE) has been widely employed as a model to study multiple sclerosis (MS) and indeed has allowed some important advances in our comprehension of MS pathogenesis. Several pieces of evidence suggest that infiltrating Th1 and Th17 lymphocytes are important players leading to CNS demyelination and lesion during the peak of murine EAE. Subsequently, effector T cell responses rapidly decline and the recovery phase of the disease strongly correlates with the expression of anti-inflammatory cytokines and the enrichment of Foxp3+ regulatory T (Treg) cells within the target organ. However, the mechanisms leading to the increased presence of Treg cells and to the remission phase of the disease are still poorly understood. Recent researches demonstrated that chemically induced amino-acid starvation response might suppress CNS immune activity. Here we verified an important participation of the general control nonrepressible 2 (GCN2), a key regulator kinase of the amino-acid starvation response, in the development of the remission phase of EAE in C57BL/6 mice. By immunizing wild type C57BL/6 (WT) and GCN2 knock-out mice (GCN2 KO) with myelin oligodendrocyte glycoprotein peptide (MOG35-55), it was noticed that GCN2 KO mice did not develop the remission phase of the disease and this was associated with higher levels of CNS inflammation and increased presence of effector T cells (Th1/Th17). These animals also showed lower frequency of Treg cells within the CNS as compared to WT animals. Higher expression of indoleamine 2,3-dioxygenase (IDO) and higher frequency of plasmacytoid dendritic cells (pDCs) were found at the peak of the disease in the CNS of WT animals. Our results suggest that the GCN2 kinase-dependent sensing of IDO activity represents an important trigger to the EAE remission phase. The IDO-mediated immunoregulatory events may include the arresting of effector T cell responses and the differentiation/expansion of Treg cells

  19. Density functional theory studies on decomposition of ethyl-palladium complexes: an important role of cationic species

    NASA Astrophysics Data System (ADS)

    Raharintsalama, Rado; Munakata, Hiroaki; Koyama, Michihisa; Kubo, Momoji; Miyamoto, Akira

    2005-05-01

    Density functional theory calculations were applied to investigate the β-hydrogen-elimination of the ethyl-palladium complexes, cis-(Me 3P) 2(Et)PdHX, where X = Cl, Br or I, to form ethene and hydrido-palladium complexes. Effects of substitution of halogen ligands and coordination of solvent molecules on geometric parameters and energies were investigated. Studies on solvated reaction intermediates revealed the agostic ethyl-palladium complexes to be important in the decomposition processes of the ethyl-palladium complexes.

  20. Growth of new particle in less and highly polluted atmosphere: Implication for an important role of NH4NO3 in growing new particles to CCN size

    NASA Astrophysics Data System (ADS)

    Zhu, Y.; Gao, H.; Duan, Z. Q.; Evans, G. J.; Yao, X.

    2013-12-01

    When new particles formed in the atmosphere grow over 50-80 nm, they will activate as cloud condensation nuclei (CCN) and lead to an increase of cloud albedo. Knowledge gaps still existed, e.g., 1) new particles under which conditions can grow to CCN size? 2) which chemicals determine the growth of new particles to CCN size? In this study, new particle formation (NPF) events were investigated at two urban sites, in Qingdao during 23 April and 31 May, 2010, and in Toronto during 1 May and 31 May, 2009, using two identical Fast Mobility Particle Sizer (FMPS). Based on the satellite column densities of air pollutants and the particulate chemical concentration in PM2.5, the site in Qingdao suffered severe air pollution while the site in Toronto is less polluted. NPF events were observed in 16 days out of 39 sampling days in Qingdao and 13 days out of 31 sampling days in Toronto. The occurrence frequency of NPF events between Qingdao (41%) and Toronto (42%) was comparable to each other. In Qingdao, the geometric mean diameter of grown nucleated particles (Dpg,i) in 15 days grew to larger than 40 nm except in one day when the growth of new particles terminated at ~20 nm. In addition, the Dpg,i in 8 days out of the 15 days grew over 50 nm and it reached ~100 nm in two days. Two-phase growth of new particles was generally observed in these NPF events of Qingdao. The first-phase growth occurred in daytime and the CMAQ modeling results showed that formation of secondary organics was likely an important cause for the growth. The second-phase growth was observed at night and was associated with the increased concentrations of NH4+ and NO3-, implying that NH4NO3 condensation played an important role in the growth. In Toronto, NPF events in 4 days followed with the growth of new particles <~20 nm while new particles grew up to ~40 nm in the remaining NPF events. A slight growth of new particles at night was observed only in 3-day NPF events when the increased concentrations of

  1. Ethylene glycol poisoning in three dogs: Importance of early diagnosis and role of hemodialysis as a treatment option.

    PubMed

    Schweighauser, A; Francey, T

    2016-02-01

    Poisoning with ethylene glycol as contained in antifreeze can rapidly lead to irreversible acute renal failure and other organ damage. It carries a grave prognosis unless diagnosed early and adequate treatment is initiated within 8 hours of ingestion. Toxicity of ethylene glycol is related to the production of toxic metabolites by the enzyme alcohol dehydrogenase (ADH), leading to early signs of severe polyuria (PU) and polydipsia (PD), gastritis, ataxia and central nervous depression, followed by progressive dehydration, and ultimately oligoanuric renal failure. In addition to general supportive care, therapeutic interventions must include either antidotes blocking ADH-mediated metabolism or blood purification techniques to remove both the parent compound and the toxic metabolites. The goal of this case report is to describe three cases of acute antifreeze intoxication in dogs, and to discuss treatment options available for this poisoning. PMID:27145686

  2. A Monogalactosyldiacylglycerol Synthase Found in the Green Sulfur Bacterium Chlorobaculum tepidum Reveals Important Roles for Galactolipids in Photosynthesis[W

    PubMed Central

    Masuda, Shinji; Harada, Jiro; Yokono, Makio; Yuzawa, Yuichi; Shimojima, Mie; Murofushi, Kazuhiro; Tanaka, Hironori; Masuda, Hanako; Murakawa, Masato; Haraguchi, Tsuyoshi; Kondo, Maki; Nishimura, Mikio; Yuasa, Hideya; Noguchi, Masato; Oh-oka, Hirozo; Tanaka, Ayumi; Tamiaki, Hitoshi; Ohta, Hiroyuki

    2011-01-01

    Monogalactosyldiacylglycerol (MGDG), which is conserved in almost all photosynthetic organisms, is the most abundant natural polar lipid on Earth. In plants, MGDG is highly accumulated in the chloroplast membranes and is an important bulk constituent of thylakoid membranes. However, precise functions of MGDG in photosynthesis have not been well understood. Here, we report a novel MGDG synthase from the green sulfur bacterium Chlorobaculum tepidum. This enzyme, MgdA, catalyzes MGDG synthesis using UDP-Gal as a substrate. The gene encoding MgdA was essential for this bacterium; only heterozygous mgdA mutants could be isolated. An mgdA knockdown mutation affected in vivo assembly of bacteriochlorophyll c aggregates, suggesting the involvement of MGDG in the construction of the light-harvesting complex called chlorosome. These results indicate that MGDG biosynthesis has been independently established in each photosynthetic organism to perform photosynthesis under different environmental conditions. We complemented an Arabidopsis thaliana MGDG synthase mutant by heterologous expression of MgdA. The complemented plants showed almost normal levels of MGDG, although they also had abnormal morphological phenotypes, including reduced chlorophyll content, no apical dominance in shoot growth, atypical flower development, and infertility. These observations provide new insights regarding the importance of regulated MGDG synthesis in the physiology of higher plants. PMID:21764989

  3. Memory for Medication Side Effects in Younger and Older Adults: The Role of Subjective and Objective Importance

    PubMed Central

    Friedman, Michael C.; McGillivray, Shannon; Murayama, Kou; Castel, Alan D.

    2014-01-01

    Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age. PMID:25331278

  4. Isolation of chromatin from dysfunctional telomeres reveals an important role for Ring1b in NHEJ-mediated chromosome fusions.

    PubMed

    Bartocci, Cristina; Diedrich, Jolene K; Ouzounov, Iliana; Li, Julia; Piunti, Andrea; Pasini, Diego; Yates, John R; Lazzerini Denchi, Eros

    2014-05-22

    When telomeres become critically short, DNA damage response factors are recruited at chromosome ends, initiating a cellular response to DNA damage. We performed proteomic isolation of chromatin fragments (PICh) in order to define changes in chromatin composition that occur upon onset of acute telomere dysfunction triggered by depletion of the telomere-associated factor TRF2. This unbiased purification of telomere-associated proteins in functional or dysfunctional conditions revealed the dynamic changes in chromatin composition that take place at telomeres upon DNA damage induction. On the basis of our results, we describe a critical role for the polycomb group protein Ring1b in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusions. We show that cells with reduced levels of Ring1b have a reduced ability to repair uncapped telomeric chromatin. Our data represent an unbiased isolation of chromatin undergoing DNA damage and are a valuable resource to map the changes in chromatin composition in response to DNA damage activation. PMID:24813883

  5. The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ.

    PubMed

    Zhang, Yahui; Li, Wanjie; Chu, Mi; Chen, Hengye; Yu, Haoyuan; Fang, Chaoguang; Sun, Ningze; Wang, Qiming; Luo, Tian; Luo, Kaiju; She, Xueping; Zhang, Mengqian; Yang, Dong

    2016-06-01

    Candida albicans is an opportunistic human pathogen, and its pathogenicity is associated with hyphal formation. Previous studies have shown that at neutral-to-alkaline pH, hyphal growth is dependent on the Rim101 pathway whose activation requires Snf7, a member of the ESCRT system. In this work, we described the purification and characterization of the C. albicans Vps4, an AAA ATPase required for recycling of the ESCRTs. Its role on hyphal growth has been investigated. Our data suggest deletion of Vps4 decreases overall hyphal growth at pH 7 and increases the growth of multiple hyphae induced by serum, which indicates that the ESCRTs may make a Rim101-independent contribution to hyphal growth. Furthermore, DBeQ, an inhibitor of the AAA ATPase p97, was shown to inhibit the ATPase activity of Vps4 with an IC50 of about 11.5 μM. To a less degree, it also inhibits hyphal growth. Our work may provide a new strategy to control C. albicans infection. PMID:26700222

  6. Role of the microenvironment in mantle cell lymphoma: IL-6 is an important survival factor for the tumor cells

    PubMed Central

    Zhang, Liang; Yang, Jing; Qian, Jianfei; Li, Haiyan; Romaguera, Jorge E.; Kwak, Larry W.; Wang, Michael

    2012-01-01

    Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma frequently involved in the lymph nodes, bone marrow, spleen, and gastrointestinal tract. We examined the role of IL-6 in MCL. Human MCL cells expressed the membrane gp130 and soluble gp80, and some of them also secreted IL-6. Neutralizing autocrine IL-6 and/or blocking IL-6 receptors in IL-6+/gp80+ MCL cells inhibited cell growth, enhanced the rate of spontaneous apoptosis, and increased sensitivity to chemotherapy drugs. For IL-6− or gp80low MCL cells, paracrine or exogenous IL-6 or gp80 protected the cells from stress-induced death. Knockdown of gp80 in gp80high MCL cells rendered the cells more sensitive to chemotherapy drugs, even in the presence of exogenous IL-6. In contrast, overexpression of gp80 in gp80low/IL-6+ MCL cells protected the cells from chemotherapy drug-induced apoptosis in vitro and compromised the therapeutic effect of chemotherapy in vivo. IL-6 activated the Jak2/STAT3 and PI3K/Akt pathways in MCL, and the inhibition of these pathways completely or partially abrogated IL-6–mediated protection of MCL cells. Hence, our study identifies IL-6 as a key cytokine for MCL growth and survival and suggests that targeting the IL-6 pathway may be a novel way to improve the efficacy of chemotherapy in MCL patients. PMID:22968454

  7. [A functionally important Tyr-89 residue in Saccharomyces cerevisiae pyrophosphatase. II. A possible role in the mechanism of enzyme action].

    PubMed

    Raznikov, A V; Steriopolo, N A; Skliankina, V A; Avaeva, S M

    1992-08-01

    Earlier it has been demonstrated that inactivation of inorganic pyrophosphatase (PPase) of S. cerevisiae by 7-chloro-4-nitronbenzofurasane is due to modification of Tyr89. The effect of pH and active center ligands on this reaction has been studied. It was found that pK for Tyr89 does not exceed 8.5; the phosphate-metal complex binding to the high affinity center protects Tyr89 from inactivation. Activating ions (Mg2+ and Zn2+) do not influence the inactivation, whereas the PPase inhibitor, Ca2+, enhances this process after saturation of the high affinity binding site. Saturation of two binding sites with Ca2+ has a protective effect on the enzyme. An increase in the rate of Tyr89 binding to the inhibitor in the presence of low concentrations of Ca2+ is due to the decrease of Tyr89 pK. The data obtained suggest that Tyr89 is located near the high affinity binding site for phosphate. The high reactivity of Tyr89 and its tight binding in the active center point to the presence of a hydrogen bondage with the substrate and suggest a role of a proton donor whose acceptor is the product of the enzymatic reaction, i.e., phosphate. PMID:1327191

  8. Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis.

    PubMed

    Marín, N; Eixarch, H; Mansilla, M J; Rodríguez-Martín, E; Mecha, M; Guaza, C; Álvarez-Cermeño, J C; Montalban, X; Villar, L M; Espejo, C

    2014-02-01

    Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood-brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139-151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE. PMID:24188195

  9. Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis

    PubMed Central

    Marín, N; Eixarch, H; Mansilla, M J; Rodríguez-Martín, E; Mecha, M; Guaza, C; Álvarez-Cermeño, J C; Montalban, X; Villar, L M; Espejo, C

    2014-01-01

    Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is an autoimmune disorder in which activated T cells cross the blood–brain barrier (BBB) to initiate an inflammatory response that leads to demyelination and axonal damage. The key mechanisms responsible for disease initiation are still unknown. We addressed this issue in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is widely known that EAE manifests only in certain strains when immunized with myelin proteins or peptides. We studied the differential immune responses induced in two mouse strains that are susceptible or resistant to EAE induction when they are immunized with the 139–151 peptide of proteolipid protein, an encephalitogenic peptide capable of inducing EAE in the susceptible strain. The adequate combination of major histocompatibility complex alleles and myelin peptides triggered in susceptible mice a T helper type 17 (Th17) response capable of inducing the production of high-affinity anti-myelin immunoglobulin (Ig)G antibodies. These were not detected in resistant mice, despite immunization with the encephalitogenic peptide in junction with complete Freund's adjuvant and pertussis toxin, which mediate BBB disruption. These data show the pivotal role of Th17 responses and of high-affinity anti-myelin antibodies in EAE induction and that mechanisms that prevent their appearance can contribute to resistance to EAE. PMID:24188195

  10. Inventory of H2O in the ancient Martian regolith from Northwest Africa 7034: The important role of Fe oxides

    NASA Astrophysics Data System (ADS)

    Muttik, Nele; McCubbin, Francis M.; Keller, Lindsay P.; Santos, Alison R.; McCutcheon, Whitney A.; Provencio, Paula P.; Rahman, Zia; Shearer, Charles K.; Boyce, Jeremy W.; Agee, Carl B.

    2014-12-01

    Water-rich Martian regolith breccia Northwest Africa (NWA) 7034 was analyzed by Fourier transform infrared spectroscopy and transmission electron microscopy to determine the inventory and phase distribution of H2O (used herein to refer to both molecular H2O and OH- structural components in hydrous minerals). Hydrous Fe oxide phases (hydromaghemite and an unidentified nanocrystalline Fe-bearing oxide phase observed with hydromaghemite) and phyllosilicates (saponite) were identified as the primary mineralogic hosts for H2O with a minor contribution from Cl-rich apatite. Based on mass balance calculations and modal abundances of minerals constrained by powder X-ray diffraction and petrography, we can account for the entire 6000 ppm H2O measured in bulk rock analyses of NWA 7034. This H2O is distributed evenly between hydrous Fe-rich oxides and phyllosilicates, indicating that Fe oxides could be as important as phyllosilicates for H2O storage in Martian surface material.

  11. Localizing transcripts to single cells suggests an important role of uncultured deltaproteobacteria in the termite gut hydrogen economy

    PubMed Central

    Rosenthal, Adam Z.; Zhang, Xinning; Lucey, Kaitlyn S.; Ottesen, Elizabeth A.; Trivedi, Vikas; Choi, Harry M. T.; Pierce, Niles A.; Leadbetter, Jared R.

    2013-01-01

    Identifying microbes responsible for particular environmental functions is challenging, given that most environments contain an uncultivated microbial diversity. Here we combined approaches to identify bacteria expressing genes relevant to catabolite flow and to locate these genes within their environment, in this case the gut of a “lower,” wood-feeding termite. First, environmental transcriptomics revealed that 2 of the 23 formate dehydrogenase (FDH) genes known in the system accounted for slightly more than one-half of environmental transcripts. FDH is an essential enzyme of H2 metabolism that is ultimately important for the assimilation of lignocellulose-derived energy by the insect. Second, single-cell PCR analysis revealed that two different bacterial types expressed these two transcripts. The most commonly transcribed FDH in situ is encoded by a previously unappreciated deltaproteobacterium, whereas the other FDH is spirochetal. Third, PCR analysis of fractionated gut contents demonstrated that these bacteria reside in different spatial niches; the spirochete is free-swimming, whereas the deltaproteobacterium associates with particulates. Fourth, the deltaproteobacteria expressing FDH were localized to protozoa via hybridization chain reaction-FISH, an approach for multiplexed, spatial mapping of mRNA and rRNA targets. These results underscore the importance of making direct vs. inference-based gene–species associations, and have implications in higher termites, the most successful termite lineage, in which protozoa have been lost from the gut community. Contrary to expectations, in higher termites, FDH genes related to those from the protozoan symbiont dominate, whereas most others were absent, suggesting that a successful gene variant can persist and flourish after a gut perturbation alters a major environmental niche. PMID:24043823

  12. SBP2 plays an important role in the virulence changes of different artificial mutants of Streptococcus suis.

    PubMed

    Yu, Yanfei; Qian, Yunyun; Du, Dechao; Xu, Chenyang; Dai, Chen; Li, Quan; Liu, Hanze; Shao, Jing; Wu, Zongfu; Zhang, Wei

    2016-05-24

    Streptococcus suis (SS) is an important bacterial zoonotic pathogen, which can cause infections in pigs and humans. However, the pathogenesis of this bacterium remains unclear, even though some putative virulence factors (VFs) have been reported. Comparative proteomics could be used to identify markers that can distinguish bacterial strains with different virulence; however, the application of this method is restricted by the genome diversities existing in different strains. In this study, two mutants, WT ΔpepT and WT ΔrfeA, which were generated from the same wild-type (WT) strain, ZY05719, and showed opposite virulence tendencies, were constructed. Combining two proteomics assays, two-dimensional difference gel electrophoresis (2D-DIGE) and label-free proteomics, we identified 38 differentially abundant proteins in the mutants compared with their parent, including five known VFs of S. suis and 33 novel elements. One of the novel proteins, a putative pilus protein, named SBP2, was considered as the most promising VF, because SBP2 was not only linked with the known VFs in the virulence interaction network and was proposed to be located on the cell surface, but also showed enriched distribution among highly virulent strains of SS. SBP2 could also bind fibronectin and laminin, two important extracellular matrix proteins of the host, to facilitate the process of adhesion. Thus, spb2 was identified as encoding a promising virulence-associated candidate associated with the pathogenesis of SS, and a comprehensive virulence interaction network of SS was established for the first time. PMID:27077729

  13. Localizing transcripts to single cells suggests an important role of uncultured deltaproteobacteria in the termite gut hydrogen economy.

    PubMed

    Rosenthal, Adam Z; Zhang, Xinning; Lucey, Kaitlyn S; Ottesen, Elizabeth A; Trivedi, Vikas; Choi, Harry M T; Pierce, Niles A; Leadbetter, Jared R

    2013-10-01

    Identifying microbes responsible for particular environmental functions is challenging, given that most environments contain an uncultivated microbial diversity. Here we combined approaches to identify bacteria expressing genes relevant to catabolite flow and to locate these genes within their environment, in this case the gut of a "lower," wood-feeding termite. First, environmental transcriptomics revealed that 2 of the 23 formate dehydrogenase (FDH) genes known in the system accounted for slightly more than one-half of environmental transcripts. FDH is an essential enzyme of H2 metabolism that is ultimately important for the assimilation of lignocellulose-derived energy by the insect. Second, single-cell PCR analysis revealed that two different bacterial types expressed these two transcripts. The most commonly transcribed FDH in situ is encoded by a previously unappreciated deltaproteobacterium, whereas the other FDH is spirochetal. Third, PCR analysis of fractionated gut contents demonstrated that these bacteria reside in different spatial niches; the spirochete is free-swimming, whereas the deltaproteobacterium associates with particulates. Fourth, the deltaproteobacteria expressing FDH were localized to protozoa via hybridization chain reaction-FISH, an approach for multiplexed, spatial mapping of mRNA and rRNA targets. These results underscore the importance of making direct vs. inference-based gene-species associations, and have implications in higher termites, the most successful termite lineage, in which protozoa have been lost from the gut community. Contrary to expectations, in higher termites, FDH genes related to those from the protozoan symbiont dominate, whereas most others were absent, suggesting that a successful gene variant can persist and flourish after a gut perturbation alters a major environmental niche. PMID:24043823

  14. FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice.

    PubMed

    Zhang, Ting; Kim, Dae Hyun; Xiao, Xiangwei; Lee, Sojin; Gong, Zhenwei; Muzumdar, Radhika; Calabuig-Navarro, Virtu; Yamauchi, Jun; Harashima, Hideyoshi; Wang, Rennian; Bottino, Rita; Alvarez-Perez, Juan Carlos; Garcia-Ocaña, Adolfo; Gittes, George; Dong, H Henry

    2016-03-01

    β-Cell compensation is an essential mechanism by which β-cells increase insulin secretion for overcoming insulin resistance to maintain euglycemia in obesity. Failure of β-cells to compensate for insulin resistance contributes to insulin insufficiency and overt diabetes. To understand the mechanism of β-cell compensation, we characterized the role of forkhead box O1 (FoxO1) in β-cell compensation in mice under physiological and pathological conditions. FoxO1 is a key transcription factor that serves as a nutrient sensor for integrating insulin signaling to cell metabolism, growth, and proliferation. We showed that FoxO1 improved β-cell compensation via 3 distinct mechanisms by increasing β-cell mass, enhancing β-cell glucose sensing, and augmenting β-cell antioxidative function. These effects accounted for increased glucose-stimulated insulin secretion and enhanced glucose tolerance in β-cell-specific FoxO1-transgenic mice. When fed a high-fat diet, β-cell-specific FoxO1-transgenic mice were protected from developing fat-induced glucose disorder. This effect was attributable to increased β-cell mass and function. Furthermore, we showed that FoxO1 activity was up-regulated in islets, correlating with the induction of physiological β-cell compensation in high-fat-induced obese C57BL/6J mice. These data characterize FoxO1 as a pivotal factor for orchestrating physiological adaptation of β-cell mass and function to overnutrition and obesity. PMID:26727107

  15. CCR5 plays an important role in resolving an inflammatory response to single-walled carbon nanotubes.

    PubMed

    Park, Eun-Jung; Roh, Jinkyu; Kim, Soo Nam; Kim, Younghun; Han, Sang-Bae; Hong, Jin Tae

    2013-08-01

    Owing to the development of new materials and technology, the pollutants in the environment are becoming more varied and complex over time. In our previous study using ICR mice, we suggested that a single intratracheal instillation of single-walled carbon nanotubes (SWCNTs) induced early lung fibrosis and subchronic tissue damage. In the present study, to investigate the role of CCR5 in inflammatory responses to the uptake of SWCNTs, we compared BAL (Bronchoalveolar lavage) cell composition, cell cycles, cytokines, cell phenotypes, inflammatory response-related proteins, cell surface receptors and histopathology using CCR5 knockout (KO) and wild-type mice. Results showed that the distribution of neutrophils in BAL fluid significantly decreased in KO mice. The expression of apoptosis-related proteins including caspase-3, p53, phospho-p53, p21 and cleaved PARP, TGF βl and mesothelin markedly increased in KO mice compared with wild-type mice. Histopathological lesions were also more frequently noted in KO mice. Moreover, the secretion of IL-13 and IL-17 with IL-6 significantly increased in KO mice compared with wild-type mice, whereas that of IL-12 significantly decreased in comparison to wild-type mice. The distribution of B cells and CD8+ T cells was predominant in the inflammatory responses in KO mice, whereas that of T cells and CD4+ T cells was predominant in the inflammatory responses in wild-type mice. Furthermore, the expression of CCR4 and CCR7 significantly increased in KO mice. Based on these results, we suggest that the absence of CCR5 delays the resolution of inflammatory responses triggered by SWCNTs inflowing into the lungs and shifts inflammatory response for SWCNTs clearance from Th1-type to Th2-type. PMID:22438032

  16. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity.

    PubMed

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina; Staeheli, Peter; Hartmann, Rune; Jensen, Uffe B; Dagnaes-Hansen, Frederik; Thomsen, Allan R; Chen, Zhi; Haugen, Harald; Klucher, Kevin; Paludan, Søren R

    2008-02-15

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda was restricted to a narrow subset of cells, including plasmacytoid dendritic cells and epithelial cells. To examine the role of type III IFN in antiviral defense, we generated IL-28Ralpha-deficient mice. These mice were indistinguishable from wild-type mice with respect to clearance of a panel of different viruses, whereas mice lacking the type I IFN receptor (IFNAR(-/-)) were significantly impaired. However, the strong antiviral activity evoked by treatment of mice with TLR3 or TLR9 agonists was significantly reduced in both IL-28RA(-/-) and IFNAR(-/-) mice. The type I IFN receptor system has been shown to mediate positive feedback on IFN-alphabeta expression, and we found that the type I IFN receptor system also mediates positive feedback on IFN-lambda expression, whereas IL-28Ralpha signaling does not provide feedback on either type I or type III IFN expression in vivo. Finally, using bone-marrow chimeric mice we showed that TLR-activated antiviral defense requires expression of IL-28Ralpha only on nonhemopoietic cells. In this compartment, epithelial cells responded to IFN-lambda and directly restricted virus replication. Our data suggest type III IFN to target a specific subset of cells and to contribute to the antiviral response evoked by TLRs. PMID:18250457

  17. Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs.

    PubMed

    Ricaño-Ponce, Isis; Zhernakova, Daria V; Deelen, Patrick; Luo, Oscar; Li, Xingwang; Isaacs, Aaron; Karjalainen, Juha; Di Tommaso, Jennifer; Borek, Zuzanna Agnieszka; Zorro, Maria M; Gutierrez-Achury, Javier; Uitterlinden, Andre G; Hofman, Albert; van Meurs, Joyce; Netea, Mihai G; Jonkers, Iris H; Withoff, Sebo; van Duijn, Cornelia M; Li, Yang; Ruan, Yijun; Franke, Lude; Wijmenga, Cisca; Kumar, Vinod

    2016-04-01

    Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases. PMID:26898941

  18. Thermoregulation of individual paper wasps ( Polistes dominula) plays an important role in nest defence and dominance battles

    NASA Astrophysics Data System (ADS)

    Höcherl, Nicole; Tautz, Jürgen

    2015-06-01

    Paper wasps, like Polistes dominula, are considered as primitively eusocial. Hence, they are often used as model species for studies about the evolution of eusociality and dominance hierarchies. However, our knowledge about basic physiological processes in these wasps remains limited. In particular, the thermoregulation of individual wasps in their natural habitat has not yet been investigated in detail. We conducted a comprehensive field study to test their ability to respond to external hazards with elevated thorax temperatures. We presented artificial threats by applying smoke or carbon dioxide simulating fire and predator attacks, respectively, and monitored the thorax temperature of wasps on the nest using infrared thermography. We found that P. dominula workers recognized smoke and CO2 and reacted almost instantaneously and simultaneously with an increase of their thorax temperature. The maximal thorax temperature was reached about 65 s after the application of both stressors, but subsequently, the wasps showed a different behaviour pattern. No rise of the thorax temperature was detectable after an air blast was applied or in wasps resting on the nest. These observations provide evidence that P. dominula is able to heat up its thorax and that thermoregulation is employed in escape and defence reactions. Additionally, we investigated the thorax temperatures of queens during dominance battles. We found that the thorax temperature of the dominant queens rose up to 5 °C compared to that of subordinate queens that attacked the former, suggesting that the dominant queen defends herself as well as her nest.

  19. Fundamental studies and development of nickel-catalyzed trifluoromethylthiolation of aryl chlorides: active catalytic species and key roles of ligand and traceless MeCN additive revealed.

    PubMed

    Yin, Guoyin; Kalvet, Indrek; Englert, Ulli; Schoenebeck, Franziska

    2015-04-01

    A catalytic protocol to convert aryl and heteroaryl chlorides to the corresponding trifluoromethyl sulfides is reported herein. It relies on a relatively inexpensive Ni(cod)2/dppf (cod = 1,5-cyclooctadiene; dppf = 1,1'-bis(diphenylphosphino)ferrocene) catalyst system and the readily accessible coupling reagent (Me4N)SCF3. Our computational and experimental mechanistic data are consistent with a Ni(0)/Ni(II) cycle and inconsistent with Ni(I) as the reactive species. The relevant intermediates were prepared, characterized by X-ray crystallography, and tested for their catalytic competence. This revealed that a monomeric tricoordinate Ni(I) complex is favored for dppf and Cl whose role was unambiguously assigned as being an off-cycle catalyst deactivation product. Only bidentate ligands with wide bite angles (e.g., dppf) are effective. These bulky ligands render the catalyst resting state as [(P-P)Ni(cod)]. The latter is more reactive than Ni(P-P)2, which was found to be the resting state for ligands with smaller bite angles and suffers from an initial high-energy dissociation of one ligand prior to oxidative addition, rendering the system unreactive. The key to effective catalysis is hence the presence of a labile auxiliary ligand in the catalyst resting state. For more challenging substrates, high conversions were achieved via the employment of MeCN as a traceless additive. Mechanistic data suggest that its beneficial role lies in decreasing the energetic span, therefore accelerating product formation. Finally, the methodology has been applied to synthetic targets of pharmaceutical relevance. PMID:25790253

  20. The dual role of CD4 T helper cells in the infection dynamics of HIV and their importance for vaccination.

    PubMed

    Altes, H Korthals; Wodarz, D; Jansen, V A A

    2002-02-21

    Given the role of the CD4 T helper cells in the development of memory CTL precursors, it seems beneficial to boost the CD4 T helper response in the context of vaccination against the human immunodeficiency virus (HIV). However, CD4 T cells are also the preferred targets of infection by HIV. Here, we address the question as to whether it is advantageous to stimulate the CD4 T helper cell response, as this will increase the pool of potential target cells of infection. To do so we formulated a mathematical model describing the interactions between virus-infected cells, susceptible cells, HIV-specific CD4 helper T cells, and CTL precursor (CTLp) and effector cells (CTLe). The effect of increased initial CD4 helper and CTLp numbers on the outcome of infection, as well as the effect on viral set point of increased CD4 T helper growth rate, CTL responsiveness and the rate at which CTLp and CTLe are produced were studied. We found that only when the virus has a low basic reproductive number does the number of CTLp and CD4 T helper cells at the moment of infection influence the outcome of infection. In this situation, high initial T helper and CTL numbers can switch the outcome from full-blown infection to virus control. However, this holds for virus with infectivity in a limited range, and current estimates of virus infectivity suggest that it is higher. In that case, only a vaccination protocol that increases CTL responsiveness, ideally in combination with the rate of production of CD4 T helper cells, may offer a solution as it can reduce the viral set point considerably. If brought under a certain level, the viral population might be unable to replicate any further. However, changing these parameters of the immune response is only beneficial when infection is controlled by CTL in the long term. When a CD4 lymphoproliferative response is mounted but the CTL response is not maintained, increasing the CD4 T helper growth rate is deleterious. PMID:11851372

  1. A One Billion Year Martian Climate Model: The Importance of Seasonally Resolved Polar Caps and the Role of Wind

    NASA Technical Reports Server (NTRS)

    Armstrong, J. C.; Leovy, C. B.; Quinn, T. R.; Haberle, R. M.; Schaeffer, J.

    2003-01-01

    is remarkable static over time, and decreases both at high and low obliquity. Also, from our one billion year orbital model, we present new results on the fraction of time Mars is expected to experience periods of high and low obliquity. Finally, using GCM runs at a variety of pressures, we examine the likely role of wind erosion under an early more massive Martian atmosphere.

  2. Carboxyl-Terminal SSLKG Motif of the Human Cystinosin-LKG Plays an Important Role in Plasma Membrane Sorting

    PubMed Central

    Taranta, Anna; Petrini, Stefania; Venditti, Rossella; Rocchetti, Maria Teresa; Rega, Laura Rita; Corallini, Serena; Gesualdo, Loreto; De Matteis, Maria Antonietta; Emma, Francesco

    2016-01-01

    Cystinosin mediates an ATP-dependent cystine efflux from lysosomes and causes, if mutated, nephropathic cystinosis, a rare inherited lysosomal storage disease. Alternative splicing of the last exon of the cystinosin sequence produces the cystinosin-LKG isoform that is characterized by a different C-terminal region causing changes in the subcellular distribution of the protein. We have constructed RFP-tagged proteins and demonstrated by site-directed mutagenesis that the carboxyl-terminal SSLKG sequence of cystinosin-LKG is an important sorting motif that is required for efficient targeting the protein to the plasma membrane, where it can mediate H+ coupled cystine transport. Deletion of the SSLKG sequence reduced cystinosin-LKG expression in the plasma membrane and cystine transport by approximately 30%, and induced significant accumulation of the protein in the Golgi apparatus and in lysosomes. Cystinosin-LKG, unlike the canonical isoform, also moves to the lysosomes by the indirect pathway, after endocytic retrieval from the plasma membrane, mainly by a clathrin-mediated endocytosis. Nevertheless, silencing of AP-2 triggers the clathrin-independent endocytosis, showing the complex adaptability of cystinosin-LKG trafficking. PMID:27148969

  3. Imported Malaria in Portugal 2000–2009: A Role for Hospital Statistics for Better Estimates and Surveillance

    PubMed Central

    Dias, Sara S.; Baptista, João Luis; Torgal, Jorge

    2014-01-01

    Background. Although eradicated in Portugal, malaria keeps taking its toll on travelers and migrants from endemic countries. Disease notification is mandatory but is compromised by underreporting. Methods. A retrospective study on malaria hospitalizations for 10 consecutive years (2000–2009) was conducted. Data on hospitalizations and notifications were obtained from Central Administration of Health System and Health Protection Agency, respectively. For data selection ICD-9 CM and ICD-10 were used: codes 084*, 647.4, and B50–B54. Variables were gender, age, agent and origin of infection, length of stay (LOS), lethality, and comorbidities. Analysis included description, hypothesis testing, and regression. Results. There were 2003 malaria hospitalizations and 480 notified hospitalized cases, mainly in young male adults. P. falciparum was the main agent of infection acquired mainly in sub-Saharan Africa. Lethality was 1.95% and mean LOS was 8.09 days. Older age entailed longer LOS and increased lethality. Discussion. From 2000 to 2009, there were 2003 malaria hospitalizations with decreasing annual incidence, these numbers being remarkably higher than those notified. The national database of diagnosis related groups, reflecting hospitalizations on NHS hospitals, may be an unexplored complementary source for better estimates on imported malaria. PMID:25548715

  4. Surface texture and priming play important roles in predator recognition by the red-backed shrike in field experiments.

    PubMed

    Němec, Michal; Syrová, Michaela; Dokoupilová, Lenka; Veselý, Petr; Šmilauer, Petr; Landová, Eva; Lišková, Silvie; Fuchs, Roman

    2015-01-01

    We compared the responses of the nesting red-backed shrikes (Lanius collurio) to three dummies of a common nest predator, the Eurasian jay (Garrulus glandarius), each made from a different material (stuffed, plush, and silicone). The shrikes performed defensive behaviour including attacks on all three dummies. Nevertheless, the number of attacks significantly decreased from the stuffed dummy through the plush dummy and finally to the silicone dummy. Our results show that wild birds use not only colours but also other surface features as important cues for recognition and categorization of other bird species. Moreover, the silicone dummy was attacked only when presented after the stuffed or plush dummy. Thus, we concluded that the shrikes recognized the jay only the stuffed (with feathered surface) and plush (with hairy surface) dummies during the first encounter. Recognition of the silicon dummy (with glossy surface) was facilitated by previous encounters with the more accurate model. This process resembles the effect of perceptual priming, which is widely described in the literature on humans. PMID:25107529

  5. Carboxyl-Terminal SSLKG Motif of the Human Cystinosin-LKG Plays an Important Role in Plasma Membrane Sorting.

    PubMed

    Bellomo, Francesco; Taranta, Anna; Petrini, Stefania; Venditti, Rossella; Rocchetti, Maria Teresa; Rega, Laura Rita; Corallini, Serena; Gesualdo, Loreto; De Matteis, Maria Antonietta; Emma, Francesco

    2016-01-01

    Cystinosin mediates an ATP-dependent cystine efflux from lysosomes and causes, if mutated, nephropathic cystinosis, a rare inherited lysosomal storage disease. Alternative splicing of the last exon of the cystinosin sequence produces the cystinosin-LKG isoform that is characterized by a different C-terminal region causing changes in the subcellular distribution of the protein. We have constructed RFP-tagged proteins and demonstrated by site-directed mutagenesis that the carboxyl-terminal SSLKG sequence of cystinosin-LKG is an important sorting motif that is required for efficient targeting the protein to the plasma membrane, where it can mediate H+ coupled cystine transport. Deletion of the SSLKG sequence reduced cystinosin-LKG expression in the plasma membrane and cystine transport by approximately 30%, and induced significant accumulation of the protein in the Golgi apparatus and in lysosomes. Cystinosin-LKG, unlike the canonical isoform, also moves to the lysosomes by the indirect pathway, after endocytic retrieval from the plasma membrane, mainly by a clathrin-mediated endocytosis. Nevertheless, silencing of AP-2 triggers the clathrin-independent endocytosis, showing the complex adaptability of cystinosin-LKG trafficking. PMID:27148969

  6. Protein translocase of the outer mitochondrial membrane: role of import receptors in the structural organization of the TOM complex.

    PubMed

    Model, Kirstin; Prinz, Thorsten; Ruiz, Teresa; Radermacher, Michael; Krimmer, Thomas; Kühlbrandt, Werner; Pfanner, Nikolaus; Meisinger, Chris

    2002-02-22

    The mitochondrial outer membrane contains a multi-subunit machinery responsible for the specific recognition and translocation of precursor proteins. This translocase of the outer membrane (TOM) consists of three receptor proteins, Tom20, Tom22 and Tom70, the channel protein Tom40, and several small Tom proteins. Single-particle electron microscopy analysis of the Neurospora TOM complex has led to different views with two or three stain-filled centers resembling channels. Based on biochemical and electron microscopy studies of the TOM complex isolated from yeast mitochondria, we have discovered the molecular reason for the different number of channel-like structures. The TOM complex from wild-type yeast contains up to three stain-filled centers, while from a mutant yeast selectively lacking Tom20, the TOM complex particles contain only two channel-like structures. From mutant mitochondria lacking Tom22, native electrophoresis separates an approximately 80 kDa subcomplex that consists of Tom40 only and is functional for accumulation of a precursor protein. We conclude that while Tom40 forms the import channels, the two receptors Tom22 and Tom20 are required for the organization of Tom40 dimers into larger TOM structures. PMID:11866524

  7. Membrane cholesterol plays an important role in enteropathogen adhesion and the activation of innate immunity via flagellin-TLR5 signaling.

    PubMed

    Zhou, Mingxu; Duan, Qiangde; Li, Yinchau; Yang, Yang; Hardwidge, Philip R; Zhu, Guoqiang

    2015-08-01

    Lipid rafts are cholesterol- and sphingolipid-rich ordered microdomains distributed in the plasma membrane that participates in mammalian signal transduction pathways. To determine the role of lipid rafts in mediating interactions between enteropathogens and intestinal epithelial cells, membrane cholesterol was depleted from Caco-2 and IPEC-J2 cells using methyl-β-cyclodextrin. Cholesterol depletion significantly reduced Escherichia coli and Salmonella enteritidis adhesion and invasion into intestinal epithelial cells. Complementation with exogenous cholesterol restored bacterial adhesion to basal levels. We also evaluated the role of lipid rafts in the activation of Toll-like receptor 5 signaling by bacterial flagellin. Depleting membrane cholesterol reduced the ability of purified recombinant E. coli flagellin to activate TLR5 signaling in intestinal cells. These data suggest that both membrane cholesterol and lipid rafts play important roles in enteropathogen adhesion and contribute to the activation of innate immunity via flagellin-TLR5 signaling. PMID:25935453

  8. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  9. Does atmospheric CO2 seasonality play an important role in governing the air-sea flux of CO2?

    NASA Astrophysics Data System (ADS)

    Halloran, P. R.

    2012-06-01

    The amplitude, phase, and form of the seasonal cycle of atmospheric CO2 concentrations varies on many time and space scales (Peters et al., 2007). Intra-annual CO2 variation is primarily driven by seasonal uptake and release of CO2 by the terrestrial biosphere (Machta et al., 1977; Buchwitz et al., 2007), with a small (Cadule et al., 2010; Heimann et al., 1998), but potentially changing (Gorgues et al., 2010) contribution from the ocean. Variability in the magnitude, spatial distribution, and seasonal drivers of terrestrial net primary productivity (NPP) will be induced by, amongst other factors, anthropogenic CO2 release (Keeling et al., 1996), land-use change (Zimov et al., 1999) and planetary orbital variability, and will lead to changes in CO2atm seasonality. Despite CO2atm seasonality being a dynamic and prominent feature of the Earth System, its potential to drive changes in the air-sea flux of CO2 has not previously (to the best of my knowledge) been explored. It is important that we investigate the impact of CO2atm seasonality change, and the potential for carbon-cycle feedbacks to operate through the modification of the CO2atm seasonal cycle, because the decision had been made to prescribe CO2atm concentrations (rather than emissions) within model simulations for the fifth IPCC climate assessment (Taylor et al., 2009). In this study I undertake ocean-model simulations within which different magnitude CO2atm seasonal cycles are prescribed. These simulations allow me to examine the effect of a change in CO2atm seasonal cycle magnitude on the air-sea CO2 flux. I then use an off-line model to isolate the drivers of the identified air-sea CO2 flux change, and propose mechanisms by which this change may come about. Three mechanisms are identified by which co-variability of the seasonal cycles in atmospheric CO2 concentration, and seasonality in sea-ice extent, wind-speed and ocean temperature, could potentially lead to changes in the air-sea flux of CO2 at mid

  10. RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection

    PubMed Central

    Thien, Peiling; Xu, Shengli; Lam, Kong-Peng; Liu, Ding Xiang

    2011-01-01

    Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1) infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I), melanoma differentiation associated gene-5 (MDA-5) and Toll-like receptor-3 (TLR3). These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3), substantial production of IFN-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus. PMID:21245912

  11. Partial Loss of Genomic Imprinting Reveals Important Roles for Kcnq1 and Peg10 Imprinted Domains in Placental Development

    PubMed Central

    Koppes, Erik; Himes, Katherine P.; Chaillet, J. Richard

    2015-01-01

    Mutations in imprinted genes or their imprint control regions (ICRs) produce changes in imprinted gene expression and distinct abnormalities in placental structure, indicating the importance of genomic imprinting to placental development. We have recently shown that a very broad spectrum of placental abnormalities associated with altered imprinted gene expression occurs in the absence of the oocyte–derived DNMT1o cytosine methyltransferase, which normally maintains parent-specific imprinted methylation during preimplantation. The absence of DNMT1o partially reduces inherited imprinted methylation while retaining the genetic integrity of imprinted genes and their ICRs. Using this novel system, we undertook a broad and inclusive approach to identifying key ICRs involved in placental development by correlating loss of imprinted DNA methylation with abnormal placental phenotypes in a mid-gestation window (E12.5-E15.5). To these ends we measured DNA CpG methylation at 15 imprinted gametic differentially methylated domains (gDMDs) that overlap known ICRs using EpiTYPER-mass array technology, and linked these epigenetic measurements to histomorphological defects. Methylation of some imprinted gDMDs, most notably Dlk1, was nearly normal in mid-gestation DNMT1o-deficient placentas, consistent with the notion that cells having lost methylation on these DMDs do not contribute significantly to placental development. Most imprinted gDMDs however showed a wide range of methylation loss among DNMT1o-deficient placentas. Two striking associations were observed. First, loss of DNA methylation at the Peg10 imprinted gDMD associated with decreased embryonic viability and decreased labyrinthine volume. Second, loss of methylation at the Kcnq1 imprinted gDMD was strongly associated with trophoblast giant cell (TGC) expansion. We conclude that the Peg10 and Kcnq1 ICRs are key regulators of mid-gestation placental function. PMID:26241757

  12. Δ24-Sterol Methyltransferase Plays an Important Role in the Growth and Development of Sporothrix schenckii and Sporothrix brasiliensis

    PubMed Central

    Borba-Santos, Luana P.; Visbal, Gonzalo; Gagini, Thalita; Rodrigues, Anderson M.; de Camargo, Zoilo P.; Lopes-Bezerra, Leila M.; Ishida, Kelly; de Souza, Wanderley; Rozental, Sonia

    2016-01-01

    Inhibition of Δ24-sterol methyltransferase (24-SMT) in Sporothrix schenckii sensu stricto and Sporothrix brasiliensis was investigated in vitro. The effects on fungal growth and sterol composition of the 24-SMT inhibitor 22-hydrazone-imidazolin-2-yl-chol-5-ene-3β-ol (H3) were compared to those of itraconazole. MIC and MFC analysis showed that H3 was more effective than itraconazole against both species in both their filamentous and yeast forms. H3 showed fungistatic activity in a time-kill assay, with inhibitory activity stronger than that of itraconazole. GC analysis of cell sterol composition showed that sterols present in control cells (ergosterol and precursors) were completely replaced by 14α-methylated sterols after H3 exposure. Itraconazole only partially inhibited ergosterol synthesis but completely arrested synthesis of other sterols found in control cells, promoting accumulation of nine 14α-methyl sterols. Based on these results, we propose a schematic model of sterol biosynthesis pathways in S. schenckii and S. brasiliensis. Effects on cell morphology due to 24-SMT inhibition by H3 as analyzed by SEM and TEM included irregular cell shape, reduced cytoplasmic electron-density, and reduced thickness of the microfibrillar cell wall layer. Moreover, 24-SMT inhibition by H3 promoted mitochondrial disturbance, as demonstrated by alterations in MitoTracker® Red CMXRos fluorescence intensity evaluated by flow cytometry. When used in conjunction with itraconazole, H3 enhanced the effectiveness of itraconazole against all tested strains, reducing at least half (or more) the MIC values of itraconazole. In addition, cytotoxicity assays revealed that H3 was more selective toward these fungi than was itraconazole. Thus, 24-SMT inhibition by H3 was an effective antifungal strategy against S. schenckii and S. brasiliensis. Inhibition of the methylation reaction catalyzed by 24-SMT has a strong antiproliferative effect via disruption of ergosterol homeostasis

  13. Δ(24)-Sterol Methyltransferase Plays an Important Role in the Growth and Development of Sporothrix schenckii and Sporothrix brasiliensis.

    PubMed

    Borba-Santos, Luana P; Visbal, Gonzalo; Gagini, Thalita; Rodrigues, Anderson M; de Camargo, Zoilo P; Lopes-Bezerra, Leila M; Ishida, Kelly; de Souza, Wanderley; Rozental, Sonia

    2016-01-01

    Inhibition of Δ(24)-sterol methyltransferase (24-SMT) in Sporothrix schenckii sensu stricto and Sporothrix brasiliensis was investigated in vitro. The effects on fungal growth and sterol composition of the 24-SMT inhibitor 22-hydrazone-imidazolin-2-yl-chol-5-ene-3β-ol (H3) were compared to those of itraconazole. MIC and MFC analysis showed that H3 was more effective than itraconazole against both species in both their filamentous and yeast forms. H3 showed fungistatic activity in a time-kill assay, with inhibitory activity stronger than that of itraconazole. GC analysis of cell sterol composition showed that sterols present in control cells (ergosterol and precursors) were completely replaced by 14α-methylated sterols after H3 exposure. Itraconazole only partially inhibited ergosterol synthesis but completely arrested synthesis of other sterols found in control cells, promoting accumulation of nine 14α-methyl sterols. Based on these results, we propose a schematic model of sterol biosynthesis pathways in S. schenckii and S. brasiliensis. Effects on cell morphology due to 24-SMT inhibition by H3 as analyzed by SEM and TEM included irregular cell shape, reduced cytoplasmic electron-density, and reduced thickness of the microfibrillar cell wall layer. Moreover, 24-SMT inhibition by H3 promoted mitochondrial disturbance, as demonstrated by alterations in MitoTracker(®) Red CMXRos fluorescence intensity evaluated by flow cytometry. When used in conjunction with itraconazole, H3 enhanced the effectiveness of itraconazole against all tested strains, reducing at least half (or more) the MIC values of itraconazole. In addition, cytotoxicity assays revealed that H3 was more selective toward these fungi than was itraconazole. Thus, 24-SMT inhibition by H3 was an effective antifungal strategy against S. schenckii and S. brasiliensis. Inhibition of the methylation reaction catalyzed by 24-SMT has a strong antiproliferative effect via disruption of ergosterol homeostasis

  14. Rheological behavior of clay-nanoparticle hybrid-added bentonite suspensions: specific role of hybrid additives on the gelation of clay-based fluids.

    PubMed

    Jung, Youngsoo; Son, You-Hwan; Lee, Jung-Kun; Phuoc, Tran X; Soong, Yee; Chyu, Minking K

    2011-09-01

    Two different types of clay nanoparticle hybrid, iron oxide nanoparticle clay hybrid (ICH) and Al(2)O(3)-SiO(2) nanoparticle clay hybrid (ASCH), were synthesized and their effects on the rheological properties of aqueous bentonite fluids in steady state and dynamic state were explored. When ICH particles were added, bentonite particles in the fluid cross-link to form relatively well-oriented porous structure. This is attributed to the development of positively charged edge surfaces in ICH that leads to strengthening of the gel structure of the bentonite susensions. The role of ASCH particles on the interparticle association of the bentonite fluids is different from that of ICH and sensitive to pH. As pH of ASCH-added bentonite suspensions increased, the viscosity, yield stress, storage modulus, and flow stress decreased. In contrast, at low pH, the clay suspensions containing ASCH additives were coagulated and their rheological properties become close to those of ICH added bentonite fluids. A correlation between the net surface charge of the hybrid additives and the rheological properties of the fluids indicates that the embedded nanoparticles within the interlayer space control the variable charge of the edge surfaces of the platelets and determine the particles association behavior of the clay fluids. PMID:21888313

  15. The Role of Patients’ Age on Their Preferences for Choosing Additional Blood Pressure-Lowering Drugs: A Discrete Choice Experiment in Patients with Diabetes

    PubMed Central

    de Vries, Sieta T.; de Vries, Folgerdiena M.; Dekker, Thijs; Haaijer-Ruskamp, Flora M.; de Zeeuw, Dick; Ranchor, Adelita V.; Denig, Petra

    2015-01-01

    Objectives To assess whether patients’ willingness to add a blood pressure-lowering drug and the importance they attach to specific treatment characteristics differ among age groups in patients with type 2 diabetes. Materials and Methods Patients being prescribed at least an oral glucose-lowering and a blood pressure-lowering drug completed a questionnaire including a discrete choice experiment. This experiment contained choice sets with hypothetical blood pressure-lowering drugs and a no additional drug alternative, which differed in their characteristics (i.e. effects and intake moments). Differences in willingness to add a drug were compared between patients <75 years (non-aged) and ≥75 years (aged) using Pearson χ2-tests. Multinomial logit models were used to assess and compare the importance attached to the characteristics. Results Of the 161 patients who completed the questionnaire, 151 (72%) could be included in the analyses (mean age 68 years; 42% female). Aged patients were less willing to add a drug than non-aged patients (67% versus 84% respectively; P = 0.017). In both age groups, the effect on blood pressure was most important for choosing a drug, followed by the risk of adverse drug events and the risk of death. The effect on limitations due to stroke was only significant in the non-aged group. The effect on blood pressure was slightly more important in the non-aged than the aged group (P = 0.043). Conclusions Aged patients appear less willing to add a preventive drug than non-aged patients. The importance attached to various treatment characteristics does not seem to differ much among age groups. PMID:26445349

  16. The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme?

    PubMed

    Goldenberg, Larry; So, Alan; Fleshner, Neil; Rendon, Ricardo; Drachenberg, Darrel; Elhilali, Mostafa

    2009-06-01

    Normal growth and function of the prostate are contingent on the reduction of testosterone to dihydrotestosterone (DHT) by 5-alpha reductase (5-AR) enzymes types 1 and 2. It has been theorized that an overabundance of DHT may be implicated in the pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. Inhibitors of 5-AR such as dutasteride and finasteride may therefore have an important role in the prevention and treatment of BPH and prostate cancer. Dutasteride provides greater suppression of DHT than finasteride, thereby underlying the hypothesis that inhibition of both type 1 and type 2 would provide correspondingly greater protection than inhibition of type 2 alone. We review the potential significance of the 5-AR inhibitors in reducing the risk of prostate cancer according to the basic biology of prostate disease. PMID:19543428

  17. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  18. Environmental Filtering Process Has More Important Roles than Dispersal Limitation in Shaping Large-Scale Prokaryotic Beta Diversity Patterns of Grassland Soils.

    PubMed

    Cao, Peng; Wang, Jun-Tao; Hu, Hang-Wei; Zheng, Yuan-Ming; Ge, Yuan; Shen, Ju-Pei; He, Ji-Zheng

    2016-07-01

    Despite the utmost importance of microorganisms in maintaining ecosystem functioning and their ubiquitous distribution, our knowledge of the large-scale pattern of microbial diversity is limited, particularly in grassland soils. In this study, the microbial communities of 99 soil samples spanning over 3000 km across grassland ecosystems in northern China were investigated using high-throughput sequencing to analyze the beta diversity pattern and the underlying ecological processes. The microbial communities were dominated by Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, and Planctomycetes across all the soil samples. Spearman's correlation analysis indicated that climatic factors and soil pH were significantly correlated with the dominant microbial taxa, while soil microbial richness was positively linked to annual precipitation. The environmental divergence-dissimilarity relationship was significantly positive, suggesting the importance of environmental filtering processes in shaping soil microbial communities. Structural equation modeling found that the deterministic process played a more important role than the stochastic process on the pattern of soil microbial beta diversity, which supported the predictions of niche theory. Partial mantel test analysis have showed that the contribution of independent environmental variables has a significant effect on beta diversity, while independent spatial distance has no such relationship, confirming that the deterministic process was dominant in structuring soil microbial communities. Overall, environmental filtering process has more important roles than dispersal limitation in shaping microbial beta diversity patterns in the grassland soils. PMID:27072664

  19. A longitudinal investigation of the mediating role of self-esteem and body importance in the relationship between stress and body dissatisfaction in adolescent females and males.

    PubMed

    Murray, Kristen; Rieger, Elizabeth; Byrne, Don

    2013-09-01

    Body dissatisfaction is particularly prevalent during adolescence and has recently been linked to stress in females and males. However, prospective studies are needed to better understand the relationship between stress and body dissatisfaction. The present study investigates the direction of this association and the mediating role of self-esteem and body image importance. A sample of 298 adolescent females and males in Grades 7 to 10 (ages 12 to 17 years) were surveyed at two time points over a one-year period. Hierarchical regression analyses revealed that stress significantly predicted body dissatisfaction one year later. Furthermore, a multiple mediation analysis controlling for gender revealed a significant indirect effect in both cross-sectional and longitudinal models, indicating that stress predicts reductions in self-esteem and increases in body importance, which in turn predict body dissatisfaction. These findings suggest that stress, self-esteem, and body importance should be included in programmes aimed at improving body dissatisfaction. PMID:23993480

  20. Transcription of DWARF4 Plays a Crucial Role in Auxin-Regulated Root Elongation in Addition to Brassinosteroid Homeostasis in Arabidopsis thaliana

    PubMed Central

    Yoshimitsu, Yuya; Tanaka, Kiwamu; Fukuda, Wataru; Asami, Tadao; Yoshida, Shigeo; Hayashi, Ken-ichiro; Kamiya, Yuji; Jikumaru, Yusuke; Shigeta, Tomoaki; Nakamura, Yasushi; Matsuo, Tomoaki; Okamoto, Shigehisa

    2011-01-01

    The expression of DWARF4 (DWF4), which encodes a C-22 hydroxylase, is crucial for brassinosteroid (BR) biosynthesis and for the feedback control of endogenous BR levels. To advance our knowledge of BRs, we examined the effects of different plant hormones on DWF4 transcription in Arabidopsis thaliana. Semi-quantitative reverse-transcriptase PCR showed that the amount of the DWF4 mRNA precursor either decreased or increased, similarly with its mature form, in response to an exogenously applied bioactive BR, brassinolide (BL), and a BR biosynthesis inhibitor, brassinazole (Brz), respectively. The response to these chemicals in the levels of β-glucuronidase (GUS) mRNA and its enzymatic activity is similar to the response of native DWF4 mRNA in DWF4::GUS plants. Contrary to the effects of BL, exogenous auxin induced GUS activity, but this enhancement was suppressed by anti-auxins, such as α-(phenylethyl-2-one)-IAA and α-tert-butoxycarbonylaminohexyl-IAA, suggesting the involvement of SCFTIR1-mediated auxin signaling in auxin-induced DWF4 transcription. Auxin-enhanced GUS activity was observed exclusively in roots; it was the most prominent in the elongation zones of both primary and lateral roots. Furthermore, auxin-induced lateral root elongation was suppressed by both Brz application and the dwf4 mutation, and this suppression was rescued by BL, suggesting that BRs act positively on root elongation under the control of auxin. Altogether, our results indicate that DWF4 transcription plays a novel role in the BR-auxin crosstalk associated with root elongation, in addition to its role in BR homeostasis. PMID:21909364

  1. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility — A Review

    PubMed Central

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-01-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  2. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

    PubMed

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-08-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  3. Eos is redundant for T regulatory cell function, but plays an important role in IL-2 and Th17 production by CD4+ T conventional cells

    PubMed Central

    Rieder, Sadiye Amcaoglu; Metidji, Amina; Glass, Deborah Dacek; Thornton, Angela M.; Ikeda, Tohru; Morgan, Bruce A.; Shevach, Ethan M.

    2015-01-01

    Eos is a transcription factor that belongs to the Ikaros family of transcription factors. Eos has been reported to be a T regulatory cell (Treg) signature gene, to play a critical role in Treg suppressor functions, and to maintain Treg stability. We have utilized mice with a global deficiency of Eos to re-examine the role of Eos expression in both Treg and T conventional (Tconv) cells. Treg from Eos deficient (Eos−/−) mice developed normally, displayed a normal Treg phenotype, and exhibited normal suppressor function in vitro. Eos−/− Treg were as effective as Treg from wild type (WT) mice in suppression of inflammation in a model of inflammatory bowel disease. Bone marrow (BM) from Eos−/− mice was as effective as BM from WT mice in controlling T cell activation when used to reconstitute immunodeficient mice in the presence of Scurfy fetal liver cells. Surprisingly, Eos was expressed in activated Tconv cells and was required for IL-2 production, CD25 expression and proliferation in vitro by CD4+ Tconv cells. Eos−/− mice developed more severe Experimental Autoimmune Encephalomyelitis than WT mice, displayed increased numbers of effector T cells in the periphery and CNS, and amplified IL-17 production. In conclusion, our studies are not consistent with a role for Eos in Treg development and function, but demonstrate that Eos plays an important role in the activation and differentiation of Tconv cells. PMID:26062998

  4. Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming.

    PubMed

    Gao, Yawei; Chen, Jiayu; Li, Ke; Wu, Tong; Huang, Bo; Liu, Wenqiang; Kou, Xiaochen; Zhang, Yu; Huang, Hua; Jiang, Yonghua; Yao, Chao; Liu, Xiaolei; Lu, Zhiwei; Xu, Zijian; Kang, Lan; Chen, Jun; Wang, Hailin; Cai, Tao; Gao, Shaorong

    2013-04-01

    DNA methylation and demethylation have been proposed to play an important role in somatic cell reprogramming. Here, we demonstrate that the DNA hydroxylase Tet1 facilitates pluripotent stem cell induction by promoting Oct4 demethylation and reactivation. Moreover, Tet1 (T) can replace Oct4 and initiate somatic cell reprogramming in conjunction with Sox2 (S), Klf4 (K), and c-Myc (M). We established an efficient TSKM secondary reprogramming system and used it to characterize the dynamic profiles of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and gene expression during reprogramming. Our analysis revealed that both 5mC and 5hmC modifications increased at an intermediate stage of the process, correlating with a transition in the transcriptional profile. We also found that 5hmC enrichment is involved in the demethylation and reactivation of genes and regulatory regions that are important for pluripotency. Our data indicate that changes in DNA methylation and hydroxymethylation play important roles in genome-wide epigenetic remodeling during reprogramming. PMID:23499384

  5. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease

    PubMed Central

    Mogilyansky, E; Rigoutsos, I

    2013-01-01

    The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members. PMID:24212931

  6. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  7. The nuclear protein GmbZIP110 has transcription activation activity and plays important roles in the response to salinity stress in soybean

    PubMed Central

    Xu, Zhaolong; Ali, Zulfiqar; Xu, Ling; He, Xiaolan; Huang, Yihong; Yi, Jinxin; Shao, Hongbo; Ma, Hongxiang; Zhang, Dayong

    2016-01-01

    Plant basic-leucine zipper (bZIP) transcription factors play important roles in many biological processes and are involved in the regulation of salt stress tolerance. Previously, our lab generated digital gene expression profiling (DGEP) data to identify differentially expressed genes in a salt-tolerant genotype of Glycine soja (STGoGS) and a salt-sensitive genotype of Glycine max (SSGoGM). This DGEP data revealed that the expression (log2 ratio) of GmbZIP110 was up-regulated 2.76-fold and 3.38-fold in SSGoGM and STGoGS, respectively. In the present study, the salt inducible gene GmbZIP110 was cloned and characterized through phylogenetic analysis, subcellular localization and in silico transcript abundance analysis in different tissues. The functional role of this gene in salt tolerance was studied through transactivation analysis, DNA binding ability, expression in soybean composite seedlings and transgenic Arabidopsis, and the effect of GmbZIP110 on the expression of stress-related genes in transgenic Arabidopsis was investigated. We found that GmbZIP110 could bind to the ACGT motif, impact the expression of many stress-related genes and the accumulation of proline, Na+ and K+, and enhanced the salt tolerance of composite seedlings and transgenic Arabidopsis. Integrating all these results, we propose that GmbZIP110 plays a critical role in the response to salinity stress in soybean and has high potential usefulness in crop improvement. PMID:26837841

  8. The nuclear protein GmbZIP110 has transcription activation activity and plays important roles in the response to salinity stress in soybean.

    PubMed

    Xu, Zhaolong; Ali, Zulfiqar; Xu, Ling; He, Xiaolan; Huang, Yihong; Yi, Jinxin; Shao, Hongbo; Ma, Hongxiang; Zhang, Dayong

    2016-01-01

    Plant basic-leucine zipper (bZIP) transcription factors play important roles in many biological processes and are involved in the regulation of salt stress tolerance. Previously, our lab generated digital gene expression profiling (DGEP) data to identify differentially expressed genes in a salt-tolerant genotype of Glycine soja (STGoGS) and a salt-sensitive genotype of Glycine max (SSGoGM). This DGEP data revealed that the expression (log2 ratio) of GmbZIP110 was up-regulated 2.76-fold and 3.38-fold in SSGoGM and STGoGS, respectively. In the present study, the salt inducible gene GmbZIP110 was cloned and characterized through phylogenetic analysis, subcellular localization and in silico transcript abundance analysis in different tissues. The functional role of this gene in salt tolerance was studied through transactivation analysis, DNA binding ability, expression in soybean composite seedlings and transgenic Arabidopsis, and the effect of GmbZIP110 on the expression of stress-related genes in transgenic Arabidopsis was investigated. We found that GmbZIP110 could bind to the ACGT motif, impact the expression of many stress-related genes and the accumulation of proline, Na(+) and K(+), and enhanced the salt tolerance of composite seedlings and transgenic Arabidopsis. Integrating all these results, we propose that GmbZIP110 plays a critical role in the response to salinity stress in soybean and has high potential usefulness in crop improvement. PMID:26837841

  9. A role for dZIP89B in Drosophila dietary zinc uptake reveals additional complexity in the zinc absorption process.

    PubMed

    Richards, Christopher D; Warr, Coral G; Burke, Richard

    2015-12-01

    Dietary zinc is the principal source of zinc in eukaryotes, with its uptake and distribution controlled by a complex network of numerous membrane-spanning transport proteins. Dietary absorption is achieved by members of the SLC39A (ZIP) gene family, which encode proteins that are generally responsible for the movement of zinc into the cytosol. ZIP4 is thought to be the primary mammalian zinc uptake gene in the small intestine, with mutations in this gene causing the zinc deficiency disease Acrodermatitis enteropathica. In Drosophila, dual knockdown of the major dietary zinc uptake genes dZIP42C.1 (dZIP1) and dZIP42C.2 (dZIP2) results in a severe sensitivity to zinc-deficient media. However, the symptoms associated with ZIP4 loss can be reversed by zinc supplementation and dZIP42C.1 and 2 knockdown has minimal effect under normal dietary conditions, suggesting that additional pathways for zinc absorption exist in both mammals and flies. This study provides evidence that dZIP89B is an ideal candidate for this role in Drosophila, encoding a low-affinity zinc uptake transporter active in the posterior midgut. Flies lacking dZIP89B, while viable and apparently healthy, show indications of low midgut zinc levels, including reduced metallothionein B expression and compensatory up-regulation of dZIP42C.1 and 2. Furthermore dZIP89B mutants display a dramatic resistance to toxic dietary zinc levels which is abrogated by midgut-specific restoration of dZIP89B activity. We postulate that dZIP89B works in concert with the closely related dZIP42C.1 and 2 to ensure optimal zinc absorption under a range of dietary conditions. PMID:26545796

  10. Mutations in Mtr4 Structural Domains Reveal Their Important Role in Regulating tRNAiMet Turnover in Saccharomyces cerevisiae and Mtr4p Enzymatic Activities In Vitro

    PubMed Central

    Li, Yan; Burclaff, Joseph; Anderson, James T.

    2016-01-01

    RNA processing and turnover play important roles in the maturation, metabolism and quality control of a large variety of RNAs thereby contributing to gene expression and cellular health. The TRAMP complex, composed of Air2p, Trf4p and Mtr4p, stimulates nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae. The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core. The helicase core contains highly conserved helicase domains RecA-1 and 2, and two structural domains of unclear functions, winged helix domain (WH) and ratchet domain. How the structural domains (arch, WH and ratchet domain) coordinate with the helicase domains and what roles they are playing in regulating Mtr4p helicase activity are unknown. We created a library of Mtr4p structural domain mutants for the first time and screened for those defective in the turnover of TRAMP and exosome substrate, hypomodified tRNAiMet. We found these domains regulate Mtr4p enzymatic activities differently through characterizing the arch domain mutants K700N and P731S, WH mutant K904N, and ratchet domain mutant R1030G. Arch domain mutants greatly reduced Mtr4p RNA binding, which surprisingly did not lead to significant defects on either in vivo tRNAiMet turnover, or in vitro unwinding activities. WH mutant K904N and Ratchet domain mutant R1030G showed decreased tRNAiMet turnover in vivo, as well as reduced RNA binding, ATPase and unwinding activities of Mtr4p in vitro. Particularly, K904 was found to be very important for steady protein levels in vivo. Overall, we conclude that arch domain plays a role in RNA binding but is largely dispensable for Mtr4p enzymatic activities, however the structural domains in the helicase core significantly contribute to Mtr4p ATPase and unwinding activities. PMID:26820724

  11. Mutations in Mtr4 Structural Domains Reveal Their Important Role in Regulating tRNAiMet Turnover in Saccharomyces cerevisiae and Mtr4p Enzymatic Activities In Vitro.

    PubMed

    Li, Yan; Burclaff, Joseph; Anderson, James T

    2016-01-01

    RNA processing and turnover play important roles in the maturation, metabolism and quality control of a large variety of RNAs thereby contributing to gene expression and cellular health. The TRAMP complex, composed of Air2p, Trf4p and Mtr4p, stimulates nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae. The Mtr4 protein structure is composed of a helicase core and a novel so-called arch domain, which protrudes from the core. The helicase core contains highly conserved helicase domains RecA-1 and 2, and two structural domains of unclear functions, winged helix domain (WH) and ratchet domain. How the structural domains (arch, WH and ratchet domain) coordinate with the helicase domains and what roles they are playing in regulating Mtr4p helicase activity are unknown. We created a library of Mtr4p structural domain mutants for the first time and screened for those defective in the turnover of TRAMP and exosome substrate, hypomodified tRNAiMet. We found these domains regulate Mtr4p enzymatic activities differently through characterizing the arch domain mutants K700N and P731S, WH mutant K904N, and ratchet domain mutant R1030G. Arch domain mutants greatly reduced Mtr4p RNA binding, which surprisingly did not lead to significant defects on either in vivo tRNAiMet turnover, or in vitro unwinding activities. WH mutant K904N and Ratchet domain mutant R1030G showed decreased tRNAiMet turnover in vivo, as well as reduced RNA binding, ATPase and unwinding activities of Mtr4p in vitro. Particularly, K904 was found to be very important for steady protein levels in vivo. Overall, we conclude that arch domain plays a role in RNA binding but is largely dispensable for Mtr4p enzymatic activities, however the structural domains in the helicase core significantly contribute to Mtr4p ATPase and unwinding activities. PMID:26820724

  12. Disentangling the role of atmospheric and oceanic conditions in the occurrence of major Baltic inflows: The importance of haline stratification in the Belt Sea.

    NASA Astrophysics Data System (ADS)

    Höflich, Katharina; Lehmann, Andreas; Myrberg, Kai

    2016-04-01

    The Baltic Sea is a semi-enclosed body of water connected to the North Sea only via the shallow and narrow Danish Straits. Of special importance to the salinity dynamics of the Baltic Sea are so-called major Baltic inflows (highly saline barotropic inflows), that also comprise the only process by which oxygen is supplied to below halocline water masses. Large barotropic inflows (or large volume changes) of the Baltic Sea can be identified from the sea level at Landsort, where the number of large barotropic inflows is found to exceed the number of major Baltic inflows. The occurrence of major Baltic inflows is typically attributed to a sequence of large-scale easterly and westerly atmospheric circulation patterns, that have recently also been linked to the occurrence of large barotropic inflows in general. In this context the widely accepted view that atmospheric conditions (and hence the evolution of the sea level in the North Sea - Baltic Sea system) are of exclusive importance to the occurrence of major Baltic inflows becomes questionable. In this study we attempt to disentangle the role of oceanic and atmospheric conditions to the occurrence of highly saline barotropic inflows, with special focus on the role of the hydrographic conditions in the Belt Sea. For the period 1979 - 2015 and using a realistic three-dimensional numerical ocean model of the Baltic Sea we find that the salinity of the barotropic inflow significantly depends on the availability of saline water masses in the Belt Sea. However, detailed investigation on the time evolution of the single barotropic inflow reveals differences in the rapidness and magnitude of the inflow events. Both are in fact good predictors for the salinity of the inflow, highlighting that within the set of large barotropic inflows also differing atmospheric conditions must play some role in the formation of the salinity of the inflowing water mass. In order to further specify the importance of the hydrographic conditions

  13. Protein DJ-1 and its anti-oxidative stress function play an important role in renal cell mediated response to profibrotic agents.

    PubMed

    Eltoweissy, Marwa; Dihazi, Gry H; Müller, Gerhard A; Asif, Abdul R; Dihazi, Hassan

    2016-05-24

    In the pathogenesis of renal fibrosis, oxidative stress (OS) enhances the production of reactive oxygen species (ROS) leading to sustained cell growth, inflammation, excessive tissue remodelling and accumulation, which results in the development and acceleration of renal damage. In our previous work (Eltoweissy et al., 2011) we established protein DJ-1 (PARK7) as an important ROS scavenger and key player in renal cell response to OS. In the present study we investigated the impact of profibrogenic agonists on DJ-1 and shed light on the role of this protein in renal fibrosis. Treatment of renal fibroblasts and epithelial cells with the profibrogenic agonist ANG II or PDGF resulted in a significant up-regulation of DJ-1 expression parallel to an increase in the expression of fibrosis markers. Monitoring of DJ-1 expression in kidney extract and tissue sections from a renal fibrosis mouse model (Col4a3-deficient) revealed a disease grade dependent regulation of the protein. Overexpression of DJ-1 prompted cell resistance to OS in both fibroblasts and epithelial cells. Furthermore overexpression of DJ-1, involved in ROS scavenging, in which glutamic acid 18 (E18) is mutated to either to aspartic acid (D) or glutamine (Q) resulted in a significant increase in cell death under OS in the case of E18D mutation, whereas E18Q mutation did not impact significantly the cell response to OS, revealing the importance of the acidic group for the ROS scavenging activity of the DJ-1 protein more than the nature of the amino acid itself. Affinity precipitation of interaction partners of DJ-1 and its mutants revealed an important role of annexin A1 and A5 in the mechanism of action of DJ-1 in anti-oxidative stress response. PMID:27109140

  14. Sponge Transgenic Mouse Model Reveals Important Roles for the MicroRNA-183 (miR-183)/96/182 Cluster in Postmitotic Photoreceptors of the Retina*

    PubMed Central

    Zhu, Qubo; Sun, Wenyu; Okano, Kiichiro; Chen, Yu; Zhang, Ning; Maeda, Tadao; Palczewski, Krzysztof

    2011-01-01

    MicroRNA-183 (miR-183), miR-96, and miR-182 comprising the miR-183/96/182 cluster are highly expressed in photoreceptor cells. Although in vitro data have indicated an important role for this cluster in the retina, details of its in vivo biological activity are still unknown. To observe the impact of the miR-183/96/182 cluster on retinal maintenance and light adaptation, we generated a sponge transgenic mouse model that disrupted the activities of the three-component microRNAs simultaneously and selectively in the retina. Although our morphological and functional studies showed no differences between transgenic and wild type mice under normal laboratory lighting conditions, sponge transgenic mice displayed severe retinal degeneration after 30 min of exposure to 10,000 lux light. Histological studies showed that the outer nuclear layer thickness was dramatically reduced in the superior retina of transgenic mice. Real time PCR experiments in both the sponge transgenic mouse model and different microRNA stable cell lines identified Arrdc3, Neurod4, and caspase-2 (Casp2) as probable downstream targets of this cluster, a result also supported by luciferase assay and immunoblotting analyses. Further studies indicated that expression of both the cluster and Casp2 increased in response to light exposure. Importantly, Casp2 expression was enhanced in transgenic mice, and inhibition of Casp2 partially rescued their light-induced retinal degeneration. By connecting the microRNA and apoptotic pathways, these findings imply an important role for the miR-183/96/182 cluster in acute light-induced retinal degeneration of mice. This study demonstrates a clear involvement of miRs in the physiology of postmitotic cells in vivo. PMID:21768104

  15. Tension on dsDNA bound to ssDNA-RecA filaments may play an important role in driving efficient and accurate homology recognition and strand exchange

    PubMed Central

    Vlassakis, Julea; Feinstein, Efraim; Yang, Darren; Tilloy, Antoine; Weiller, Dominic; Kates-Harbeck, Julian; Coljee, Vincent; Prentiss, Mara

    2013-01-01

    It is well known that during homology recognition and strand exchange the double stranded DNA (dsDNA) in DNA/RecA filaments is highly extended, but the functional role of the extension has been unclear. We present an analytical model that calculates the distribution of tension in the extended dsDNA during strand exchange. The model suggests that the binding of additional dsDNA base pairs to the DNA/RecA filament alters the tension in dsDNA that was already bound to the filament, resulting in a non-linear increase in the mechanical energy as a function of the number of bound base pairs. This collective mechanical response may promote homology stringency and underlie unexplained experimental results.

  16. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  17. Phosphazene additives

    SciTech Connect

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  18. Does asymmetric charge transfer play an important role as an ionization mode in low power-low pressure glow discharge mass spectrometry?

    NASA Astrophysics Data System (ADS)

    Mushtaq, S.; Steers, E. B. M.; Churchill, G.; Barnhart, D.; Hoffmann, V.; Pickering, J. C.; Putyera, K.

    2016-04-01

    We report results of comprehensive studies using the Nu Instruments Astrum high-resolution glow discharge mass spectrometer (GD-MS) and optical emission spectrometry (OES) to investigate the relative importance of discharge mechanisms, such as Penning ionization (PI) and asymmetric charge transfer (ACT), at low-power/low-pressure discharge conditions. Comparison of the ratios of the ion signals of each constituent element to that of the plasma gas shows that for oxygen, the ratio in krypton is more than ten times higher than in argon (oxygen ground state ions are produced by Kr-ACT). For many elements, the ratios are very similar but that for tungsten is higher with krypton, while for iron, the reverse holds. These effects are linked to the arrangement of ionic energy levels of the elements concerned and the resulting relative importance of ACT and PI. The GD-MS and GD-OES results have shown that the ACT process can play an important role as the ionization mode in low-power/low-pressure discharges. However, OES results have shown that the magnitude of change in spectral intensities of elements studied are dependent on the discharge conditions.

  19. The Role of Important Non-Parental Adults (VIPs) in the Lives of Older Adolescents: A Comparison of Three Ethnic Groups

    PubMed Central

    Chen, Chuansheng; Greenberger, Ellen

    2010-01-01

    Previous research has consistently documented the importance of VIPs (mentors or important non-parental adults) in the lives of adolescents. Little is known, however, about whether VIPs play the same important roles across ethnic groups and whether VIPs remain influential when adolescents are older and involved in romantic relationships. The present study compared VIPs of 355 Hispanic, Asian, and European American older adolescents (age range = 17–19 years; M = 18.7 years; 62% female). Results indicated that, despite ethnic differences in their social capital, VIPs’ psychological characteristics (e.g., warmth and acceptance, depressive symptoms, and problem behavior) were similar. VIPs were perceived to have more positive psychological profiles than parents and peers, and in some cases, romantic partners. Moreover, with a few exceptions, the associations between VIP characteristics and adolescent adjustment (e.g., self-esteem, depressive symptoms, and problem behavior) were largely similar across ethnic groups. Finally, VIPs made unique contributions to adolescents’ self-esteem and problem behaviors even after the effects of romantic partners were considered. Implications of the findings are discussed. PMID:20446024

  20. Supramolecular polymerisation in water; elucidating the role of hydrophobic and hydrogen-bond interactions† †Electronic supplementary information (ESI) available: Experimental details, characterization by IR and UV spectroscopy and dynamic light scattering, video files of optical microscopy imaging. See DOI: 10.1039/c5sm02843d Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.

    PubMed Central

    Leenders, Christianus M. A.; Baker, Matthew B.; Pijpers, Imke A. B.; Lafleur, René P. M.; Albertazzi, Lorenzo

    2016-01-01

    Understanding the self-assembly of small molecules in water is crucial for the development of responsive, biocompatible soft materials. Here, a family of benzene-1,3,5-tricarboxamide (BTA) derivatives that comprise a BTA moiety connected to an amphiphilic chain is synthesised with the aim to elucidate the role of hydrophobic and hydrogen-bonding interactions in the self-assembly of these BTAs. The amphiphilic chain consists of an alkyl chain with a length of 10, 11, or 12 methylene units, connected to a tetraethylene glycol (at the periphery). The results show that an undecyl spacer is the minimum length required for these BTAs to self-assemble into supramolecular polymers. Interestingly, exchange studies reveal only minor differences in exchange rates between BTAs containing undecyl or dodecyl spacers. Additionally, IR spectroscopy provides the first experimental evidence that hydrogen-bonding is operative and contributes to the stabilisation of the supramolecular polymers in water. PMID:26892482

  1. Manipulating crystallization with molecular additives.

    PubMed

    Shtukenberg, Alexander G; Lee, Stephanie S; Kahr, Bart; Ward, Michael D

    2014-01-01

    Given the importance of organic crystals in a wide range of industrial applications, the chemistry, biology, materials science, and chemical engineering communities have focused considerable attention on developing methods to control crystal structure, size, shape, and orientation. Tailored additives have been used to control crystallization to great effect, presumably by selectively binding to particular crystallographic surfaces and sites. However, substantial knowledge gaps still exist in the fundamental mechanisms that govern the formation and growth of organic crystals in both the absence and presence of additives. In this review, we highlight research discoveries that reveal the role of additives, either introduced by design or present adventitiously, on various stages of formation and growth of organic crystals, including nucleation, dislocation spiral growth mechanisms, growth inhibition, and nonclassical crystal morphologies. The insights from these investigations and others of their kind are likely to guide the development of innovative methods to manipulate crystallization for a wide range of materials and applications. PMID:24579880

  2. Analytic Hierarchy Process to Define the Most Important Factors and Related Technologies for Empowering Elderly People in Taking an Active Role in their Health.

    PubMed

    Fico, G; Gaeta, E; Arredondo, M T; Pecchia, L

    2015-09-01

    Successful management of health conditions in older population is determined by strategic involvement of a professional team of careers and by empowering patients and their caregivers to take over a central role and responsibility in the daily management of condition. Identifying, structuring and ranking the most important needs related to these aspects could pave the way for improved strategies in designing systems and technological solutions supporting user empowerment. This paper presents the preliminary results of a study aiming to elicit these needs. Healthcare professionals, working together in the European and Innovation Partnership on Active and Healthy Ageing (EIP-AHA) initiative, have defined a set of needs and factors that have been organized in two hierarchies around the concepts of patient activation and proactive and prepared care team, defined in the Chronic Care Model. The two hierarchies have been mapped, by a team of experts in computer science, with technologies and solutions that could facilitate the achievement of the identified needs. PMID:26254254

  3. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

    PubMed

    Trivedi, Rachana; Dihazi, Gry H; Eltoweissy, Marwa; Mishra, Durga P; Mueller, Gerhard A; Dihazi, Hassan

    2016-08-01

    Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells. PMID:27112662

  4. OsPAP10c, a novel secreted acid phosphatase in rice, plays an important role in the utilization of external organic phosphorus.

    PubMed

    Lu, Linghong; Qiu, Wenmin; Gao, Wenwen; Tyerman, Stephen D; Shou, Huixia; Wang, Chuang

    2016-10-01

    Under phosphate (Pi ) starvation, plants increase the secretion of purple acid phosphatases (PAPs) into the rhizosphere to scavenge organic phosphorus (P) for plant use. To date, only a few members of the PAP family have been characterized in crops. In this study, we identified a novel secreted PAP in rice, OsPAP10c, and investigated its role in the utilization of external organic P. OsPAP10c belongs to a monocotyledon-specific subclass of Ia group PAPs and is specifically expressed in the epidermis/exodermis cell layers of roots. Both the transcript and protein levels of OsPAP10c are strongly induced by Pi starvation. OsPAP10c overexpression increased acid phosphatase (APase) activity by more than 10-fold in the culture media and almost fivefold in both roots and leaves under Pi -sufficient and Pi -deficient conditions. This increase in APase activity further improved the plant utilization efficiency of external organic P. Moreover, several APase isoforms corresponding to OsPAP10c were identified using in-gel activity assays. Under field conditions with three different Pi supply levels, OsPAP10c-overexpressing plants had significantly higher tiller numbers and shorter plant heights. This study indicates that OsPAP10c encodes a novel secreted APase that plays an important role in the utilization of external organic P in rice. PMID:27411391

  5. Serine-scanning mutagenesis studies of the C-terminal heptad repeats in the SARS coronavirus S glycoprotein highlight the important role of the short helical region

    SciTech Connect

    Follis, Kathryn E.; York, Joanne; Nunberg, Jack H. . E-mail: jack.nunberg@umontana.edu

    2005-10-10

    The fusion subunit of the SARS-CoV S glycoprotein contains two regions of hydrophobic heptad-repeat amino acid sequences that have been shown in biophysical studies to form a six-helix bundle structure typical of the fusion-active core found in Class I viral fusion proteins. Here, we have applied serine-scanning mutagenesis to the C-terminal-most heptad-repeat region in the SARS-CoV S glycoprotein to investigate the functional role of this region in membrane fusion. We show that hydrophobic sidechains at a and d positions only within the short helical segment of the C-terminal heptad-repeat region (I1161, I1165, L1168, A1172, and L1175) are critical for cell-cell fusion. Serine mutations at outlying heptad-repeat residues that form an extended chain in the core structure (V1158, L1179, and L1182) do not affect fusogenicity. Our study provides genetic evidence for the important role of {alpha}-helical packing in promoting S glycoprotein-mediated membrane fusion.

  6. Molecular cloning and functional analysis of GbRVd, a gene in Gossypium barbadense that plays an important role in conferring resistance to Verticillium wilt.

    PubMed

    Yang, Jun; Ma, Qing; Zhang, Yan; Wang, Xingfen; Zhang, Guiyin; Ma, Zhiying

    2016-01-10

    Most of the disease resistance genes already characterized in plants encode nucleotide-binding site-leucine rich repeat (NBS-LRR) proteins that have key roles in resistance to Verticillium dahliae. Using a cDNA library and RACE protocols, we cloned a coiled-coil (CC)-NBS-LRR-type gene, GbRVd, from a resistant tetraploid cotton species, Gossypium barbadense (RVd=Resistance to V. dahliae). We also applied RT-qPCR and VIGS technologies to analyze how expression of GbRVd was induced upon attack by V. dahliae. Its 2862-bp ORF encodes a predicted protein containing 953 amino acid residues, with a predicted molecular weight of 110.17kDa and an isoelectric point of 5.87. GbRVd has three domains - CC, NBS, and LRR - and is most closely related to Gossypium raimondii RVd (88% amino acid identity). Profiling demonstrated that GbRVd is constitutively expressed in all tested tissues, and transcript levels are especially high in the leaves. In plants inoculated with V. dahliae, GbRVd was significantly up-regulated when compared with the control, with expression peaking at 48h post-inoculation. Silencing of GbRVd in cotton through VIGS dramatically down-regulated SA, NO, and H2O2 production, resulting in greater susceptibility to V. dahliae. Taken together, these results suggest that GbRVd has an important role in protecting G. barbadense against infection by V. dahliae. PMID:26407869

  7. A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes

    PubMed Central

    Li, Qi-Gang; Wu, Huan; Luo, Long-Hai; Kong, Qing-Peng

    2015-01-01

    It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs) were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer’s disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3)] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2)] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity. PMID:25793257

  8. The comER Gene Plays an Important Role in Biofilm Formation and Sporulation in both Bacillus subtilis and Bacillus cereus

    PubMed Central

    Yan, Fang; Yu, Yiyang; Wang, Luyao; Luo, Yuming; Guo, Jian-hua; Chai, Yunrong

    2016-01-01

    Bacteria adopt alternative cell fates during development. In Bacillus subtilis, the transition from planktonic growth to biofilm formation and sporulation is controlled by a complex regulatory circuit, in which the most important event is activation of Spo0A, a transcription factor and a master regulator for genes involved in both biofilm formation and sporulation. In B. cereus, the regulatory pathway controlling biofilm formation and cell differentiation is much less clear. In this study, we show that a novel gene, comER, plays a significant role in biofilm formation as well as sporulation in both B. subtilis and B. cereus. Mutations in the comER gene result in defects in biofilm formation and a delay in spore formation in the two Bacillus species. Our evidence supports the idea that comER may be part of the regulatory circuit that controls Spo0A activation. comER likely acts upstream of sda, a gene encoding a small checkpoint protein for both sporulation and biofilm formation, by blocking the phosphor-relay and thereby Spo0A activation. In summary, our studies outlined a conserved, positive role for comER, a gene whose function was previously uncharacterized, in the regulation of biofilm formation and sporulation in the two Bacillus species. PMID:27446060

  9. The comER Gene Plays an Important Role in Biofilm Formation and Sporulation in both Bacillus subtilis and Bacillus cereus.

    PubMed

    Yan, Fang; Yu, Yiyang; Wang, Luyao; Luo, Yuming; Guo, Jian-Hua; Chai, Yunrong

    2016-01-01

    Bacteria adopt alternative cell fates during development. In Bacillus subtilis, the transition from planktonic growth to biofilm formation and sporulation is controlled by a complex regulatory circuit, in which the most important event is activation of Spo0A, a transcription factor and a master regulator for genes involved in both biofilm formation and sporulation. In B. cereus, the regulatory pathway controlling biofilm formation and cell differentiation is much less clear. In this study, we show that a novel gene, comER, plays a significant role in biofilm formation as well as sporulation in both B. subtilis and B. cereus. Mutations in the comER gene result in defects in biofilm formation and a delay in spore formation in the two Bacillus species. Our evidence supports the idea that comER may be part of the regulatory circuit that controls Spo0A activation. comER likely acts upstream of sda, a gene encoding a small checkpoint protein for both sporulation and biofilm formation, by blocking the phosphor-relay and thereby Spo0A activation. In summary, our studies outlined a conserved, positive role for comER, a gene whose function was previously uncharacterized, in the regulation of biofilm formation and sporulation in the two Bacillus species. PMID:27446060

  10. Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells

    PubMed Central

    Lee, Jane Ying-Chieh; Kuo, Ching-Wen; Tsai, Shing-Ling; Cheng, Siao Muk; Chen, Shang-Hung; Chan, Hsiu-Han; Lin, Chun-Hui; Lin, Kun-Yuan; Li, Chien-Feng; Kanwar, Jagat R.; Leung, Euphemia Y.; Cheung, Carlos Chun Ho; Huang, Wei-Jan; Wang, Yi-Ching; Cheung, Chun Hei Antonio

    2016-01-01

    SAHA is a class I HDAC/HDAC6 co-inhibitor and an autophagy inducer currently undergoing clinical investigations in breast cancer patients. However, the molecular mechanism of action of SAHA in breast cancer cells remains unclear. In this study, we found that SAHA is equally effective in targeting cells of different breast cancer subtypes and tamoxifen sensitivity. Importantly, we found that down-regulation of survivin plays an important role in SAHA-induced autophagy and cell viability reduction in human breast cancer cells. SAHA decreased survivin and XIAP gene transcription, induced survivin protein acetylation and early nuclear translocation in MCF7 and MDA-MB-231 breast cancer cells. It also reduced survivin and XIAP protein stability in part through modulating the expression and activation of the 26S proteasome and heat-shock protein 90. Interestingly, targeting HDAC3 and HDAC6, but not other HDAC isoforms, by siRNA/pharmacological inhibitors mimicked the effects of SAHA in modulating the acetylation, expression, and nuclear translocation of survivin and induced autophagy in MCF7 and MDA-MB-231 cancer cells. Targeting HDAC3 also mimicked the effect of SAHA in up-regulating the expression and activity of proteasome, which might lead to the reduced protein stability of survivin in breast cancer cells. In conclusion, this study provides new insights into SAHA's molecular mechanism of actions in breast cancer cells. Our findings emphasize the complexity of the regulatory roles in different HDAC isoforms and potentially assist in predicting the mechanism of novel HDAC inhibitors in targeted or combinational therapies in the future. PMID:27065869

  11. Cysteine S-conjugate β-lyases: Important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents

    PubMed Central

    Cooper, Arthur J. L.; Krasnikov, Boris F.; Niatsetskaya, Zoya V.; Pinto, John T.; Callery, Patrick S.; Villar, Maria T.; Artigues, Antonio; Bruschi, Sam A.

    2010-01-01

    Summary Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess a good leaving group in the β-position. The end products are aminoacrylate and a sulfur-containing fragment. The aminoacrylate tautomerizes and hydrolyzes to pyruvate and ammonia. The mammalian cysteine S-conjugate β-lyases thus far identified are enzymes involved in amino acid metabolism that catalyze β-lyase reactions as non-physiological side reactions. Most are aminotransferases. In some cases the lyase is inactivated by reaction products. The cysteine S-conjugate β-lyases are of much interest to toxicologists because they play an important key role in the bioactivation (toxication) of halogenated alkenes, some of which are produced on an industrial scale and are environmental contaminants. The cysteine S-conjugate β-lyases have been reviewed in this journal previously [Cooper and Pinto, 2006]. Here we focus on more recent findings regarding: 1) the identification of enzymes associated with high-Mr cysteine S-conjugate β-lyases in the cytosolic and mitochondrial fractions of rat liver and kidney; 2) the mechanism of syncatalytic inactivation of rat liver mitochondrial aspartate aminotransferase by the nephrotoxic β-lyase substrate S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (the cysteine S-conjugate of tetrafluoroethylene); 3) toxicant channeling of reactive fragments from the active site of mitochondrial aspartate aminotransferase to susceptible proteins in the mitochondria; 4) the involvement of cysteine S-conjugate β-lyases in the metabolism/bioactivation of drugs and natural products; and 5) the role of cysteine S-conjugate β-lyases in the metabolism of selenocysteine Se-conjugates. This review emphasizes the fact that the cysteine S-conjugate β-lyases are biologically more important than hitherto appreciated. PMID:20306345

  12. Diabetes-induced upregulation of urotensin II and its receptor plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction.

    PubMed

    Tian, Lin; Li, Cai; Qi, Jiping; Fu, Peng; Yu, Xiaoyan; Li, Xiaokun; Cai, Lu

    2008-11-01

    Urotensin II (UII) was identified as the ligand for a novel G protein-coupled receptor, GPR14. UII was found not only to have a potent vasoconstrictive action but also to have profibrotic effects in the heart. The present study was to define whether UII and GPR14 also play important roles in diabetes-induced renal fibrosis and dysfunction. Diabetic rats were induced using streptozotocin, and the rat proximal tubular epithelial cells (NRK-52E) were used for the in vitro mechanism study. Results showed that expression of UII and GPR14 was significantly upregulated at both mRNA and protein levels in the diabetic kidneys compared with controls. The upregulated expressions of UII and GPR14 in the kidney were accompanied by significant increases in the renal profibrotic factor transforming growth factor (TGF)-beta1 expression, the renal extracellular matrix (fibronectin and collagen IV) accumulation, and the renal dysfunction (increases in urinal N-acetyl-beta-d-glucosaminidase content, 24-h urinary retinol-binding protein excretion rate, and decrease in creatinine clearance rate). Exposure of NRK-52E cells to 10(-8) mol/l UII for 48 h caused a significant increase of TGF-beta1, but not ANG II, production that was GPR14- and calcium-dependent, since GPR14 small-interfering RNA and calcium channel blocker nimodipine or calcium chelator EDTA all could abolish the induction of TGF- beta1 by UII. Furthermore, exposure of NRK-52E cells to TGF-beta1 or ANG II also increased UII and GPR14 mRNA expressions. These results suggested that diabetes-induced upregulation of UII and GPR14, most likely through autocrine and/or paracrine mechanisms, plays an important role in TGF-beta1-mediated renal fibrosis and dysfunction. PMID:18796544

  13. Proteomics Profiling Reveals Carbohydrate Metabolic Enzymes and 14-3-3 Proteins Play Important Roles for Starch Accumulation during Cassava Root Tuberization.

    PubMed

    Wang, Xuchu; Chang, Lili; Tong, Zheng; Wang, Dongyang; Yin, Qi; Wang, Dan; Jin, Xiang; Yang, Qian; Wang, Liming; Sun, Yong; Huang, Qixing; Guo, Anping; Peng, Ming

    2016-01-01

    Cassava is one of the most important root crops as a reliable source of food and carbohydrates. Carbohydrate metabolism and starch accumulation in cassava storage root is a cascade process that includes large amounts of proteins and cofactors. Here, comparative proteomics were conducted in cassava root at nine developmental stages. A total of 154 identified proteins were found to be differentially expressed during starch accumulation and root tuberization. Many enzymes involved in starch and sucrose metabolism were significantly up-regulated, and functional classification of the differentially expressed proteins demonstrated that the majority were binding-related enzymes. Many proteins were took part in carbohydrate metabolism to produce energy. Among them, three 14-3-3 isoforms were induced to be clearly phosphorylated during storage root enlargement. Overexpression of a cassava 14-3-3 gene in Arabidopsis thaliana confirmed that the older leaves of these transgenic plants contained higher sugar and starch contents than the wild-type leaves. The 14-3-3 proteins and their binding enzymes may play important roles in carbohydrate metabolism and starch accumulation during cassava root tuberization. These results not only deepened our understanding of the tuberous root proteome, but also uncovered new insights into carbohydrate metabolism and starch accumulation during cassava root enlargement. PMID:26791570

  14. Proteomics Profiling Reveals Carbohydrate Metabolic Enzymes and 14-3-3 Proteins Play Important Roles for Starch Accumulation during Cassava Root Tuberization

    PubMed Central

    Wang, Xuchu; Chang, Lili; Tong, Zheng; Wang, Dongyang; Yin, Qi; Wang, Dan; Jin, Xiang; Yang, Qian; Wang, Liming; Sun, Yong; Huang, Qixing; Guo, Anping; Peng, Ming

    2016-01-01

    Cassava is one of the most important root crops as a reliable source of food and carbohydrates. Carbohydrate metabolism and starch accumulation in cassava storage root is a cascade process that includes large amounts of proteins and cofactors. Here, comparative proteomics were conducted in cassava root at nine developmental stages. A total of 154 identified proteins were found to be differentially expressed during starch accumulation and root tuberization. Many enzymes involved in starch and sucrose metabolism were significantly up-regulated, and functional classification of the differentially expressed proteins demonstrated that the majority were binding-related enzymes. Many proteins were took part in carbohydrate metabolism to produce energy. Among them, three 14-3-3 isoforms were induced to be clearly phosphorylated during storage root enlargement. Overexpression of a cassava 14-3-3 gene in Arabidopsis thaliana confirmed that the older leaves of these transgenic plants contained higher sugar and starch contents than the wild-type leaves. The 14-3-3 proteins and their binding enzymes may play important roles in carbohydrate metabolism and starch accumulation during cassava root tuberization. These results not only deepened our understanding of the tuberous root proteome, but also uncovered new insights into carbohydrate metabolism and starch accumulation during cassava root enlargement. PMID:26791570

  15. 24th WRSM panel discussion: {open_quotes}The role of research in nuclear regulation: The case of qualified importers{close_quotes}

    SciTech Connect

    Alonso, A.

    1997-01-01

    Scientific knowledge and technological maturity are needed to establish regulatory requirements, what also needs talent and skills. Scientists are rarely interested in regulation and regulators not always are closely connected to scientific research. This has created gaps in regulations, mainly within qualified importers. A qualified importer, in the sense of this presentation, is a country who has acquired nuclear power plants from more technologically advanced exporters but with an increasing participation of its own industry and institutions in the design, construction, component manufacture and assembly of such nuclear power plants and is fully responsible for the operation of the nuclear units and the corresponding fuel cycle. These countries have also a long standing and independent nuclear regulatory organization and the corresponding technical body. Spain is a qualified importer. In the case of Spain, it originally adopted the codes and regulations of the UE which it was a member of, as well as the codes and standards of the country from which their reactors were produced. Since Spain added KWU plants they even went to German regulations. Plant operation rested with Spain. As problems began to appear in operating plants, local research projects were funded to study the problems, aimed at immediate solutions, but also providing training for local personnel in addition to information of use for regulators. Spain has participated in many joint research projects, which have trained people, and given confidence to Spaniards involved in science and regulations. Qualified importers, like Spain, participate in research, even though it may not translate itself into regulation. Such participation will always serve to give self-confidence and independence to regulators and licensees, to better understand the adopted regulations of the most advanced countries and to solve specific problems.

  16. Deletion of a gene cluster encoding pectin degrading enzymes in Caldicellulosiruptor bescii reveals an important role for pectin in plant biomass recalcitrance

    DOE PAGESBeta

    Chung, Daehwan; Pattathil, Sivakumar; Biswal, Ajaya K.; Hahn, Michael G.; Mohnen, Debra; Westpheling, Janet

    2014-10-10

    A major obstacle, and perhaps the most important economic barrier to the effective use of plant biomass for the production of fuels, chemicals, and bioproducts, is our current lack of knowledge of how to efficiently and effectively deconstruct wall polymers for their subsequent use as feedstocks. Plants represent the most desired source of renewable energy and hydrocarbons because they fix CO2, making their use carbon neutral. Their biomass structure, however, is a barrier to deconstruction, and this is often referred to as recalcitrance. Members of the bacterial genus Caldicellulosiruptor have the ability to grow on unpretreated plant biomass and thusmore » provide an assay for plant deconstruction and biomass recalcitrance. Using recently developed genetic tools for manipulation of these bacteria, a deletion of a gene cluster encoding enzymes for pectin degradation was constructed, and the resulting mutant was reduced in its ability to grow on both dicot and grass biomass, but not on soluble sugars. The plant biomass from three phylogenetically diverse plants, Arabidopsis (a herbaceous dicot), switchgrass (a monocot grass), and poplar (a woody dicot), was used in these analyses. These biomass types have cell walls that are significantly different from each other in both structure and composition. While pectin is a relatively minor component of the grass and woody dicot substrates, the reduced growth of the mutant on all three biomass types provides direct evidence that pectin plays an important role in biomass recalcitrance. Glycome profiling of the plant material remaining after growth of the mutant on Arabidopsis biomass compared to the wild-type revealed differences in the rhamnogalacturonan I, homogalacturonan, arabinogalactan, and xylan profiles. In contrast, only minor differences were observed in the glycome profiles of the switchgrass and poplar biomass. In conclusion, the combination of microbial digestion and plant biomass analysis provides a new and

  17. Deletion of a gene cluster encoding pectin degrading enzymes in Caldicellulosiruptor bescii reveals an important role for pectin in plant biomass recalcitrance

    SciTech Connect

    Chung, Daehwan; Pattathil, Sivakumar; Biswal, Ajaya K.; Hahn, Michael G.; Mohnen, Debra; Westpheling, Janet

    2014-10-10

    A major obstacle, and perhaps the most important economic barrier to the effective use of plant biomass for the production of fuels, chemicals, and bioproducts, is our current lack of knowledge of how to efficiently and effectively deconstruct wall polymers for their subsequent use as feedstocks. Plants represent the most desired source of renewable energy and hydrocarbons because they fix CO2, making their use carbon neutral. Their biomass structure, however, is a barrier to deconstruction, and this is often referred to as recalcitrance. Members of the bacterial genus Caldicellulosiruptor have the ability to grow on unpretreated plant biomass and thus provide an assay for plant deconstruction and biomass recalcitrance. Using recently developed genetic tools for manipulation of these bacteria, a deletion of a gene cluster encoding enzymes for pectin degradation was constructed, and the resulting mutant was reduced in its ability to grow on both dicot and grass biomass, but not on soluble sugars. The plant biomass from three phylogenetically diverse plants, Arabidopsis (a herbaceous dicot), switchgrass (a monocot grass), and poplar (a woody dicot), was used in these analyses. These biomass types have cell walls that are significantly different from each other in both structure and composition. While pectin is a relatively minor component of the grass and woody dicot substrates, the reduced growth of the mutant on all three biomass types provides direct evidence that pectin plays an important role in biomass recalcitrance. Glycome profiling of the plant material remaining after growth of the mutant on Arabidopsis biomass compared to the wild-type revealed differences in the rhamnogalacturonan I, homogalacturonan, arabinogalactan, and xylan profiles. In contrast, only minor differences were observed in the glycome profiles of the switchgrass and poplar biomass. In conclusion, the combination of microbial digestion and plant biomass analysis provides a new

  18. ‘Serious thigh muscle strains’: beware the intramuscular tendon which plays an important role in difficult hamstring and quadriceps muscle strains

    PubMed Central

    Brukner, Peter; Connell, David

    2016-01-01

    Why do some hamstring and quadriceps strains take much longer to repair than others? Which injuries are more prone to recurrence? Intramuscular tendon injuries have received little attention as an element in ‘muscle strain’. In thigh muscles, such as rectus femoris and biceps femoris, the attached tendon extends for a significant distance within the muscle belly. While the pathology of most muscle injures occurs at a musculotendinous junction, at first glance the athlete appears to report pain within a muscle belly. In addition to the musculotendinous injury being a site of pathology, the intramuscular tendon itself is occasionally injured. These injuries have a variety of appearances on MRIs. There is some evidence that these injuries require a prolonged rehabilitation time and may have higher recurrence rates. Therefore, it is important to recognise the tendon component of a thigh ‘muscle strain’. PMID:26519522

  19. F1C Fimbriae Play an Important Role in Biofilm Formation and Intestinal Colonization by the Escherichia coli Commensal Strain Nissle 1917▿

    PubMed Central

    Lasaro, Melissa A.; Salinger, Nina; Zhang, Jing; Wang, Yantao; Zhong, Zhengtao; Goulian, Mark; Zhu, Jun

    2009-01-01

    Bacterial biofilm formation is thought to enhance survival in natural environments and during interaction with hosts. A robust colonizer of the human gastrointestinal tract, Escherichia coli Nissle 1917, is widely employed in probiotic therapy. In this study, we performed a genetic screen to identify genes that are involved in Nissle biofilm formation. We found that F1C fimbriae are required for biofilm formation on an inert surface. In addition, these structures are also important for adherence to epithelial cells and persistence in infant mouse colonization. The data suggest a possible connection between Nissle biofilm formation and the survival of this commensal within the host. Further study of the requirements for robust biofilm formation may improve the therapeutic efficacy of Nissle 1917. PMID:18997018

  20. Activation of P2X7 Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection

    PubMed Central

    Lee, Benjamin H.; Hwang, David M.; Palaniyar, Nades; Grinstein, Sergio; Philpott, Dana J.; Hu, Jim

    2012-01-01

    Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X7 receptor (P2X7R) is required for induction of inflammatory mediators. We also showed that ATP-P2X7R signaling regulates inflammasome activation as inhibition or deficiency of P2X7R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X7R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X7R or caspase-1 showed higher rates of survival. The improved survival in the P2X7R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the

  1. My lived experiences are more important than your probabilities: The role of individualized risk estimates for decision making about participation in the Study of Tamoxifen and Raloxifene (STAR)

    PubMed Central

    Holmberg, Christine; Waters, Erika A.; Whitehouse, Katie; Daly, Mary; McCaskill-Stevens, Worta

    2015-01-01

    Background Decision making experts emphasize that understanding and using probabilistic information is important for making informed decisions about medical treatments involving complex risk-benefit tradeoffs. Yet empirical research demonstrates that individuals may not use probabilities when making decisions. Objectives To explore decision making and the use of probabilities for decision making from the perspective of women who were risk-eligible to enroll in the Study of Tamoxifen and Raloxifene (STAR). Methods We conducted narrative interviews with 20 women who agreed to participate in STAR and 20 women who declined. The project was based on a narrative approach. Analysis included the development of summaries of each narrative, and thematic analysis with developing a coding scheme inductively to code all transcripts to identify emerging themes. Results Interviewees explained and embedded their STAR decisions within experiences encountered throughout their lives. Such lived experiences included but were not limited to breast cancer family history, personal history of breast biopsies, and experiences or assumptions about taking tamoxifen or medicines more generally. Conclusions Women’s explanations of their decisions about participating in a breast cancer chemoprevention trial were more complex than decision strategies that rely solely on a quantitative risk-benefit analysis of probabilities derived from populations In addition to precise risk information, clinicians and risk communicators should recognize the importance and legitimacy of lived experience in individual decision making. PMID:26183166

  2. In situ7Li and 133Cs nuclear magnetic resonance investigations on the role of Cs+ additive in lithium-metal deposition process

    NASA Astrophysics Data System (ADS)

    Hu, Jian Zhi; Zhao, Zhenchao; Hu, Mary Y.; Feng, Ju; Deng, Xuchu; Chen, Xilin; Xu, Wu; Liu, Jun; Zhang, Ji-Guang

    2016-02-01

    Cesium ion (Cs+) has been reported to be an effective electrolyte additive to suppress Li dendrite growth which prevents the application of lithium (Li) metal as an anode for rechargeable Li batteries. In this work, we investigated the effect of Cs+ additive on Li depositions using quantitative in situ7Li and 133Cs nuclear magnetic resonance (NMR) with planar symmetric Li cells. It's found that the addition of Cs+ can significantly enhance both the formation of well aligned Li nanorods and reversibility of the Li electrode. In situ133Cs NMR directly confirms that Cs+ migrates to Li electrode to form a positively charged electrostatic shield during the charging process. Much more electrochemical "active" Li was found in Li films deposited with Cs+ additive, while more electrochemical "dead" and thicker Li rods were identified in Li films deposited without Cs+. Combining the in situ and the previous ex-situ results, a Li deposition model has been proposed to explain these observations.

  3. STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control.

    PubMed

    Toth, Karoly; Lee, Sang R; Ying, Baoling; Spencer, Jacqueline F; Tollefson, Ann E; Sagartz, John E; Kong, Il-Keun; Wang, Zhongde; Wold, William S M

    2015-08-01

    Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as animal models. PMID

  4. STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control

    PubMed Central

    Spencer, Jacqueline F.; Tollefson, Ann E.; Sagartz, John E.; Kong, Il-Keun; Wang, Zhongde; Wold, William S. M.

    2015-01-01

    Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as animal models. PMID

  5. Mechanistic study on lung cancer mortality after radon exposure in the Wismut cohort supports important role of clonal expansion in lung carcinogenesis.

    PubMed

    Zaballa, I; Eidemüller, M

    2016-08-01

    Lung cancer mortality after radon exposure in the Wismut cohort was analyzed using the two-stage clonal expansion (TSCE) model. A total of 2996 lung cancer deaths among the 58,695 male workers were observed during the follow-up period between 1946 and 2003. Adjustment to silica exposure was performed to find a more accurate estimation of the risk of radon exposure. An additional analysis with the descriptive excess relative risk (ERR) model was carried out for comparison. The TSCE model that best describes the data is nonlinear in the clonal expansion with radon exposure and has a saturation level at an exposure rate of [Formula: see text]. The excess relative risk decreases with age and shows an inverse exposure rate effect. In comparison with the ERR model, the TSCE model predicts a considerably larger risk for low exposures rates below [Formula: see text]. Comparison to other mechanistic studies of lung cancer after exposure to alpha particles using the TSCE model reveals an extraordinary consistency in the main features of the exposure response, given the diversity in the characteristics of the cohorts and the exposure across different studies. This suggests that a nonlinear response mechanism in the clonal expansion, with some level of saturation at large exposure rates, may be playing a crucial role in the development of lung cancer after alpha particle irradiation. PMID:27334643

  6. Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes*

    PubMed Central

    Wang, Jianshe; Jiang, Jun; Zhang, Hongxia; Wang, Junping; Cai, Hua; Li, Cheng; Li, Kangbai; Liu, Jing; Guo, Xuejiang; Zou, Guangxun; Wang, Dazhi; Deng, Yiqun; Dai, Jiayin

    2011-01-01

    Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of counter-measures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3′-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and de-epoxidation of T-2 implying that other esterases and epoxide hydrolases may play dominant roles in those reactions. PMID:21685020

  7. A Putative Mitochondrial Iron Transporter MrsA in Aspergillus fumigatus Plays Important Roles in Azole-, Oxidative Stress Responses and Virulence

    PubMed Central

    Long, Nanbiao; Xu, Xiaoling; Qian, Hui; Zhang, Shizhu; Lu, Ling

    2016-01-01

    Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus. PMID:27433157

  8. A Putative Mitochondrial Iron Transporter MrsA in Aspergillus fumigatus Plays Important Roles in Azole-, Oxidative Stress Responses and Virulence.

    PubMed

    Long, Nanbiao; Xu, Xiaoling; Qian, Hui; Zhang, Shizhu; Lu, Ling

    2016-01-01

    Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus. PMID:27433157

  9. SARI, a novel target gene of glucocorticoid receptor, plays an important role in dexamethasone-mediated killing of B lymphoma cells.

    PubMed

    Huang, Yinghui; Zhou, Jie; Huang, Yan; He, Jintao; Wang, Yuting; Yang, Chaohui; Liu, Dongbo; Zhang, Li; He, Fengtian

    2016-04-01

    Dexamethasone (Dex) has been commonly used in lymphoma and leukemia treatment, but the detailed mechanisms are not fully understood. Suppressor of AP-1 regulated by interferon (SARI) has tumor-selective growth inhibitory effect. However, it's unclear whether SARI is involved in the Dex-mediated lymphoma growth suppression. In this study, we found that Dex-treated B lymphoma tissues had a higher level of SARI. Dex repressed the growth of B lymphoma cells and upregulated SARI expression by activating glucocorticoid receptor (GR) in vitro and in vivo. Silencing of SARI attenuated the Dex-mediated growth suppression of B lymphoma cells and inhibition of AP-1 activity. Reporter assays revealed that activation of GR enhanced the transcriptional activity of SARI promoter. EMSA and ChIP assays showed that GR directly bound to the ER9 element in SARI promoter region. These results for the first time demonstrated that SARI is a novel target gene of GR, and the upregulation of SARI plays an important role in Dex's killing effect on B lymphoma cells, suggesting that SARI may serve as a novel target and a potential indicator of Dex sensitivity in B lymphoma treatment. PMID:26808579

  10. Overexpression of CDR1 and CDR2 genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C mutations.

    PubMed

    Chen, L M; Xu, Y H; Zhou, C L; Zhao, J; Li, C Y; Wang, R

    2010-01-01

    This study was designed to investigate potential resistance mechanisms by studying the expression of resistant genes in 14 fluconazole-resistant Candida albicans isolates, with G487T and T916C mutations in the 14alpha-demethylase (ERG11) gene, collected from human immunodeficiency virus uninfected patients and a fluconazole-susceptible control strain. The in vitro susceptibilities of the C. albicans isolates to fluconazole were determined using the broth microdilution method and a disc diffusion assay. Expression of Candida drug resistance (CDR)1, CDR2, ERG11, fluconazole resistance (FLU)1 and multidrug resistance (MDR)1 genes was measured using real-time reverse transcription-polymerase chain reaction and evaluated relative to the expression of the control gene 18SrRNA. The CDR1 and CDR2 genes were upregulated in all the fluconazole-resistant C. albicans isolates, whereas only a few isolates showed high expression of MDR1, FLU1 and ERG11 genes compared with the control strain. In conclusion, overexpression of the CDR1 and CDR2 genes may play an important role in fluconazole-resistant C. albicans with G487T and T916C mutations. PMID:20515567

  11. Important role of the non-uniform Fe distribution for the ferromagnetism in group-IV-based ferromagnetic semiconductor GeFe

    SciTech Connect

    Wakabayashi, Yuki K.; Ohya, Shinobu; Ban, Yoshisuke; Tanaka, Masaaki

    2014-11-07

    We investigate the growth-temperature dependence of the properties of the group-IV-based ferromagnetic semiconductor Ge{sub 1−x}Fe{sub x} films (x = 6.5% and 10.5%), and reveal the correlation of the magnetic properties with the lattice constant, Curie temperature (T{sub C}), non-uniformity of Fe atoms, stacking-fault defects, and Fe-atom locations. While T{sub C} strongly depends on the growth temperature, we find a universal relationship between T{sub C} and the lattice constant, which does not depend on the Fe content x. By using the spatially resolved transmission-electron diffractions combined with the energy-dispersive X-ray spectroscopy, we find that the density of the stacking-fault defects and the non-uniformity of the Fe concentration are correlated with T{sub C}. Meanwhile, by using the channeling Rutherford backscattering and particle-induced X-ray emission measurements, we clarify that about 15% of the Fe atoms exist on the tetrahedral interstitial sites in the Ge{sub 0.935}Fe{sub 0.065} lattice and that the substitutional Fe concentration is not correlated with T{sub C}. Considering these results, we conclude that the non-uniformity of the Fe concentration plays an important role in determining the ferromagnetic properties of GeFe.

  12. Important role of catalase in the production of β-carotene by recombinant Saccharomyces cerevisiae under H2O2 stress.

    PubMed

    Yan, Guo-liang; Liang, Heng-yu; Wang, Zhi-qun; Yang, Xiao-fan; Liu, Dan; Liu, Jin-fu; Duan, Chang-qing

    2011-03-01

    The effect of H(2)O(2) supplement on cell growth and β-carotene productions in recombinant Saccharomyces cerevisiae CFW-01 and CFW-01 ctt1 deficiency in cytosolic catalase were investigated in shaking flasks. The results showed that supplement of H(2)O(2) (0.5 and 1.0 mM) can significantly stimulate the β-carotene production. However, β-carotene levels of CFW-01 ctt1Δ under 0.5 and 1 mM H(2)O(2) were 16.7 and 36.7% lower than those of CFW-01, respectively. Although lacking cytosolic catalase, no significant differences in cell growth were observed between CFW-01 ctt1Δ and CFW-01 under the same level of H(2)O(2) stress. These results suggest that β-carotene can act as an antioxidant to protect the recombinant yeast from H(2)O(2) oxidative damage in the absence of cytosolic catalase. However, catalase still plays an important role in the production of β-carotene under H(2)O(2) stress. If catalase can not timely decompose H(2)O(2), the free radicals such as OH· derived from H(2)O(2) can result in decrease of β-carotene concentration. Therefore, in the production of β-carotene by H(2)O(2) stress, not only the level of oxidative stress, but also the activities of catalase in cells should be considered. PMID:21120656

  13. Understanding the importance of conservative hypothetical protein LdBPK_070020 in Leishmania donovani and its role in subsistence of the parasite.

    PubMed

    Bhardwaj, Ruchika; Kumar, Ritesh; Singh, Sanjeev Kumar; Selvaraj, Chandrabose; Dubey, Vikash Kumar

    2016-04-15

    The genome of Leishmania donovani, the causative agent of visceral leishmaniasis, codes for approximately 65% of both conserved and non-conserved hypothetical proteins. Studies on 'conserved hypothetical' proteins are expected to reveal not only new and crucial aspects of Leishmania biochemistry, but it could also lead to discovery of novel drug candidates. Conserved hypothetical protein, LdBPK_070020, is a 31.14 kDa protein, encoded by an 810 bp gene. BLAST analysis of LdBPK_070020, performed against NCBI non-redundant database, showed 80-99% similarity with conserved hypothetical proteins of Leishmania belonging to other species. Using homologues recombination method, we have performed gene knockout of LdBPK_070020 and effects of the same were investigated on the parasite. The gene knocked out strain shows significant retardation in growth with respect to wild type. Detailed biochemical studies indicated towards important role of LdBPK_070020 in the parasite survival and growth. PMID:26926257

  14. A complex of Cox4 and mitochondrial Hsp70 plays an important role in the assembly of the cytochrome c oxidase

    PubMed Central

    Böttinger, Lena; Guiard, Bernard; Oeljeklaus, Silke; Kulawiak, Bogusz; Zufall, Nicole; Wiedemann, Nils; Warscheid, Bettina; van der Laan, Martin; Becker, Thomas

    2013-01-01

    The formation of the mature cytochrome c oxidase (complex IV) involves the association of nuclear- and mitochondria-encoded subunits. The assembly of nuclear-encoded subunits like cytochrome c oxidase subunit 4 (Cox4) into the mature complex is poorly understood. Cox4 is crucial for the stability of complex IV. To find specific biogenesis factors, we analyze interaction partners of Cox4 by affinity purification and mass spectroscopy. Surprisingly, we identify a complex of Cox4, the mitochondrial Hsp70 (mtHsp70), and its nucleotide-exchange factor mitochondrial GrpE (Mge1). We generate a yeast mutant of mtHsp70 specifically impaired in the formation of this novel mtHsp70-Mge1-Cox4 complex. Strikingly, the assembly of Cox4 is strongly decreased in these mutant mitochondria. Because Cox4 is a key factor for the biogenesis of complex IV, we conclude that the mtHsp70-Mge1-Cox4 complex plays an important role in the formation of cytochrome c oxidase. Cox4 arrests at this chaperone complex in the absence of mature complex IV. Thus the mtHsp70-Cox4 complex likely serves as a novel delivery system to channel Cox4 into the assembly line when needed. PMID:23864706

  15. cDNA-AFLP analysis reveals heat shock proteins play important roles in mediating cold, heat, and drought tolerance in Ammopiptanthus mongolicus.

    PubMed

    Guo, Huiming; Li, Zhaochun; Zhou, Meiliang; Cheng, Hongmei

    2014-03-01

    Ammopiptanthus mongolicus (Maxim.ex kom.) Cheng F. is the only evergreen broadleaf shrub endemic to the desert of central Asian and it can survive at drought, salt, and alkali stress. It is believed that A. mongolicus is an important germplasm containing abiotic-tolerance genes. In order to identify drought-, cold-, and heat-responsive genes and to gain a better understanding of stress responses in A. mongolicus, genome-wide investigation of drought-, cold-, and heat-responsive genes was performed in A. mongolicus using cDNA-amplified fragment length polymorphism. Selective amplification with 240 primer combinations generated 5,000 differentially expressed transcript derived fragments (TDFs). Of these, 201 TDFs with differential expression patterns were excised from gels, reamplified by PCR, and sequenced. The gene expression patterns of 11 regulated genes were further investigated by semiquantitative reverse transcriptase polymerase chain reaction analysis. Sequencing and similarity analysis revealed that TDFs present homologies chiefly with proteins involved in various abiotic and biotic stress and developmental responses. The information presented in this study reveals that heat shock proteins play an active role in mediating drought, cold, and heat tolerance in A. mongolicus. PMID:24241624

  16. Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors

    PubMed Central

    Zheng, Yingfeng; Murphy, Leigh C.

    2016-01-01

    Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M. PMID:26778927

  17. The Sand Seas of northern China: Important sinks and sources of global sediment fluxes and their changing roles during different climate conditions of Late Quaternary

    NASA Astrophysics Data System (ADS)

    Yang, X.

    2014-12-01

    Although the occurrence of aeolian sands in sedimentary sequences has been widely used as indicators of desert formation or proxies of desert climate, one should be aware that accumulation of aeolian sands does occur along river channels, in lake shores not necessarily associated with arid environment. Our ongoing geomorphological and paleoenvironmental studies in the deserts of northern China reconfirm that formation of sand seas is dependent on not only erodibility (arising from bare surface due to aridity) and wind power but more importantly sand availability related to sediment cycles under interactions between fluvial, lacustrine and aeolian processes. Here we present our ongoing geomorphological and paleoclimatic research on the Late Quaternary landscape and climatic changes in the Taklamkan Desert of northwestern China, the largest sand sea of China in arid zone, and in the Hunshandake Sandy Land at the east part of the Asian mid-latitude desert belt under semiarid climate. We find out that the occurrence of tall sand dunes in the over 300,000 km2 large Taklamakan Sand Sea is closely related to the sites of intensive fluvial sedimentation and convergence zone of surface winds. In the case of Hunshandake, the dunes (although much smaller) mainly occur along the shorelines of the former lake basins, and sediment sources are generally limited because of open hydrological systems in the south and east portions of this desert. The sedimentological and geomorphological records suggest that the climate has changed between arid and less-arid conditions in both of these deserts during Late Quaternary. Under wetter conditions the Taklamakan acts as an important sink of sediments brought by rivers with headwaters in the Tibetan Plateau and Tianshan, while under more arid conditions it acts as an important global sediment source whose dust is transported not only to East Asia and Pacific but also to Greenland ice via westerlies. The Hunshandake has the same pattern of

  18. TaLHY, a 1R-MYB Transcription Factor, Plays an Important Role in Disease Resistance against Stripe Rust Fungus and Ear Heading in Wheat

    PubMed Central

    Zhang, Zijin; Chen, Jieming; Su, Yongying; Liu, Hanmei; Chen, Yanger; Luo, Peigao; Du, Xiaogang; Wang, Dan; Zhang, Huaiyu

    2015-01-01

    LHY (late elongated hypocotyl) is an important gene that regulates and controls biological rhythms in plants. Additionally, LHY is highly expressed in the SSH (suppression subtractive hybridization) cDNA library-induced stripe rust pathogen (CYR32) in our previous research. To identify the function of the LHY gene in disease resistance against stripe rust, we used RACE-PCR technology to clone TaLHY in the wheat variety Chuannong19. The cDNA of TaLHY is 3085 bp long with an open reading frame of 1947 bp. TaLHY is speculated to encode a 70.3 kDa protein of 648 amino acids , which has one typical plant MYB-DNA binding domain; additionally, phylogenetic tree shows that TaLHY has the highest homology with LHY of Brachypodium distachyon(BdLHY-like). Quantitative fluorescence PCR indicates that TaLHY has higher expression in the leaf, ear and stem of wheat but lower expression in the root. Infestation of CYR32 can result in up-regulated expression of TaLHY, peaking at 72 h. Using VIGS (virus-induced gene silencing) technology to disease-resistant wheat in the fourth leaf stage, plants with silenced TaLHY cannot complete their heading stage. Through the compatible interaction with the stripe rust physiological race CYR32, Chuannong 19 loses its immune capability toward the stripe rust pathogen, indicating that TaLHY may regulate and participate in the heading of wheat, as well as the defense responses against stripe rust infection. PMID:26010918

  19. The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [⁶⁸Ga(DOTATATE)].

    PubMed

    Oehlke, Elisabeth; Lengkeek, Nigel A; Le, Van So; Pellegrini, Paul A; Greguric, Ivan; Weiner, Ron

    2016-01-01

    [(68)Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe(3+) and Cu(2+), potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [(68)Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe(3+) by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu(2+) and Fe(3+) to Cu(+) and Fe(2+) respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe(3+) from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe(3+) (0.25 mM) and 100 nmol Cu(2+) (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3. PMID:26405839

  20. The role of methanol addition to water samples in reducing analyte adsorption and matrix effects in liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Wei; Liu, Yucan; Duan, Jinming; Saint, Christopher P; Mulcahy, Dennis

    2015-04-10

    Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis coupled simply with water filtering before injection has proven to be a simple, economic and time-saving method for analyzing trace-level organic pollutants in aqueous environments. However, the linearity, precision and detection limits of such methods for late-eluting analytes were found to be much poorer than for early-eluting ones due to adsorption of the analytes in the operating system, such as sample vial, flow path and sample loop, creating problems in quantitative analysis. Addition of methanol (MeOH) into water samples as a modifier was shown to be effective in alleviating or even eliminating the negative effect on signal intensity for the late-eluting analytes and at the same time being able to reduce certain matrix effects for real water samples. Based on the maximum detection signal intensity obtained on desorption of the analytes with MeOH addition, the ratio of the detection signal intensity without addition of MeOH to the maximum intensity can be used to evaluate the effectiveness of methanol addition. Accordingly, the values of <50%, 50-80%, 80-120% could be used to indicate strong, medium and no effects, respectively. Based on this concept, an external matrix-matched calibration method with the addition of MeOH has been successfully established for analyzing fifteen pesticides with diverse physico-chemical properties in surface and groundwater with good linearity (r(2): 0.9929-0.9996), precision (intra-day relative standard deviation (RSD): 1.4-10.7%, inter-day RSD: 1.5-9.4%), accuracy (76.9-126.7%) and low limits of detection (0.003-0.028μg/L). PMID:25748540

  1. Cell division and endoreduplication play important roles in stem swelling of tuber mustard (Brassica juncea Coss. var. tumida Tsen et Lee).

    PubMed

    Shi, H; Wang, L L; Sun, L T; Dong, L L; Liu, B; Chen, L P

    2012-11-01

    We investigated spatio-temporal variations in cell division and the occurrence of endoreduplication in cells of tuber mustard stems during development. Cells in the stem had 8C nuclei (C represents DNA content of a two haploid genome), since it is an allotetraploid species derived from diploid Brassica rapa (AA) and B. nigra (BB), thus indicating the occurrence of endoreduplication. Additionally, we observed a dynamic change of cell ploidy in different regions of the swollen stems, with a decrease in 4C proportion in P4-1 and a sharp increase in 8C cells that became the dominant cell type (86.33% at most) in the inner pith cells. Furthermore, cDNAs of 14 cell cycle genes and four cell expansion genes were cloned and their spatial transcripts analysed in order to understand their roles in stem development. The expression of most cell cycle genes peaked in regions of the outer pith (P2 or P3), some genes regulating S/G2 and G2/M (BjCDKB1;2, BjCYCB1;1 and BjCYCB1;2) significantly decrease in P5 and P6, while G1/S regulators (BjE2Fa, BjE2Fb and BjE2Fc) showed a relative high expression level in the inner pith (P5) where cells were undergoing endoreduplication. Coincidentally, BjXTH1and BjXTH2 were exclusively expressed in the endoreduplicated cells. Our results suggest that cells of outer pith regions (P2 and P3) mainly divide for cell proliferation, while cells of the inner pith expand through endoreduplication. Endoreduplication could trigger expression of BjXTH1 and BjXTH2 and thus function in cell expansion of the pith tissue. PMID:22639957

  2. Strong Scaling and a Scarcity of Small Earthquakes Point to an Important Role for Thermal Runaway in Intermediate-Depth Earthquake Mechanics

    NASA Astrophysics Data System (ADS)

    Barrett, S. A.; Prieto, G. A.; Beroza, G. C.

    2015-12-01

    There is strong evidence that metamorphic reactions play a role in enabling the rupture of intermediate-depth earthquakes; however, recent studies of the Bucaramanga Nest at a depth of 135-165 km under Colombia indicate that intermediate-depth seismicity shows low radiation efficiency and strong scaling of stress drop with slip/size, which suggests a dramatic weakening process, as proposed in the thermal shear instability model. Decreasing stress drop with slip and low seismic efficiency could have a measurable effect on the magnitude-frequency distribution of small earthquakes by causing them to become undetectable at substantially larger seismic moment than would be the case if stress drop were constant. We explore the population of small earthquakes in the Bucaramanga Nest using an empirical subspace detector to push the detection limit to lower magnitude. Using this approach, we find ~30,000 small, previously uncatalogued earthquakes during a 6-month period in 2013. We calculate magnitudes for these events using their relative amplitudes. Despite the additional detections, we observe a sharp deviation from a Gutenberg-Richter magnitude frequency distribution with a marked deficiency of events at the smallest magnitudes. This scarcity of small earthquakes is not easily ascribed to the detectability threshold; tests of our ability to recover small-magnitude waveforms of Bucaramanga Nest earthquakes in the continuous data indicate that we should be able to detect events reliably at magnitudes that are nearly a full magnitude unit smaller than the smallest earthquakes we observe. The implication is that nearly 100,000 events expected for a Gutenberg-Richter MFD are "missing," and that this scarcity of small earthquakes may provide new support for the thermal runaway mechanism in intermediate-depth earthquake mechanics.

  3. A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection.

    PubMed

    Tzeng, Te-Chen; Schattgen, Stefan; Monks, Brian; Wang, Donghai; Cerny, Anna; Latz, Eicke; Fitzgerald, Katherine; Golenbock, Douglas T

    2016-07-12

    Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We have developed transgenic mice that ectopically express the fluorescent adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and characterized the formation of assembled inflammasome complexes ("specks") in primary cells and tissues. In addition to hematopoietic cells, we have found that a stromal population in the lung tissues formed specks during the early phase of influenza infection, whereas myeloid cells showed speck formation after 2 days. In a peritonitis and group B streptococcus infection model, a higher percentage of neutrophils formed specks at early phases of infection, while dendritic cells formed specks at later time points. Furthermore, speck-forming cells underwent pyroptosis and extensive release of specks to the extracellular milieu in vivo. These data underscore the importance of free specks during inflammatory processes in vivo. PMID:27346360

  4. The role of molybdenum additions and prior deformation on acicular ferrite formation in microalloyed Nb-Ti low-carbon line-pipe steels

    SciTech Connect

    Tang Zhenghua Stumpf, Waldo

    2008-06-15

    Microstructures in Nb-Ti-microalloyed line-pipe steels with various molybdenum additions, consisted mostly of acicular ferrite plus polygonal ferrite after hot rolling and rapid cooling. Structure-sensitive surface relief after etching on shadowed extraction replicas, allowed quantification of the acicular and polygonal ferrite contents. Continuous cooling transformation diagrams of two alloys, one Mo-free and the other containing 0.22% Mo, were determined for cooling rates from 0.1 to 40 deg. C s{sup -1} without and with prior deformation of the austenite below the nil-recrystallisation temperature. Molybdenum additions slightly enhanced the acicular ferrite formation in the strain-free austenite whereas prior deformation had a much greater effect, and strongly promoted acicular ferrite formation in both alloys. Thin foil electron microscopy of acicular ferrite in these low-inclusion content alloys showed a preference for parallel acicular ferrite laths with less 'chaotically' nucleated laths.

  5. The potential of operando XAFS for determining the role and structure of noble metal additives in metal oxide based gas sensors

    NASA Astrophysics Data System (ADS)

    Grunwaldt, Jan-Dierk; Hübner, Michael; Koziej, Dorota; Barsan, Nicolae; Weimar, Udo

    2013-04-01

    Noble metal additives significantly improve the performance of SnO2 based sensors. Recently, it has been found that X-ray absorption spectroscopy is an excellent tool to identify their structure under sensing conditions, despite of the low concentrations and the rather thin (50 μm) and highly porous layers. For this purpose a new in situ approach has been established and here we highlight the potential with an overview on the results of Pd-, Pt-, and Au-additives in SnO2-based sensors at work. Emphasis was laid on recording the structure (by XANES and EXAFS) and performance at the same time. In contrast to earlier studies, Pd- and Pt-additives were observed to be in oxidized and finely dispersed state under sensing conditions excluding a spillover from metallic noble metal particles. However, Au was mainly present as metallic particles in the sensing SnO2-layer. For the Pt- and Au-doped SnO2-layers high energy-resolved fluorescence detected X-ray absorption spectra (HERFD-XAS) were recorded not only to minimize the lifetime-broadening but also to eliminate the Au- and Pt-fluorescence effectively and to record range-extended EXAFS.

  6. Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease.

    PubMed

    Pottier, Cyril; Bieniek, Kevin F; Finch, NiCole; van de Vorst, Maartje; Baker, Matt; Perkersen, Ralph; Brown, Patricia; Ravenscroft, Thomas; van Blitterswijk, Marka; Nicholson, Alexandra M; DeTure, Michael; Knopman, David S; Josephs, Keith A; Parisi, Joseph E; Petersen, Ronald C; Boylan, Kevin B; Boeve, Bradley F; Graff-Radford, Neill R; Veltman, Joris A; Gilissen, Christian; Murray, Melissa E; Dickson, Dennis W; Rademakers, Rosa

    2015-07-01

    Frontotemporal lobar degeneration with TAR DNA-binding protein 43 inclusions (FTLD-TDP) is the most common pathology associated with frontotemporal dementia (FTD). Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) and mutations in progranulin (GRN) are the major known genetic causes of FTLD-TDP; however, the genetic etiology in the majority of FTLD-TDP remains unexplained. In this study, we performed whole-genome sequencing in 104 pathologically confirmed FTLD-TDP patients from the Mayo Clinic brain bank negative for C9ORF72 and GRN mutations and report on the contribution of rare single nucleotide and copy number variants in 21 known neurodegenerative disease genes. Interestingly, we identified 5 patients (4.8 %) with variants in optineurin (OPTN) and TANK-binding kinase 1 (TBK1) that are predicted to be highly pathogenic, including two double mutants. Case A was a compound heterozygote for mutations in OPTN, carrying the p.Q235* nonsense and p.A481V missense mutation in trans, while case B carried a deletion of OPTN exons 13-15 (p.Gly538Glufs*27) and a loss-of-function mutation (p.Arg117*) in TBK1. Cases C-E carried heterozygous missense mutations in TBK1, including the p.Glu696Lys mutation which was previously reported in two amyotrophic lateral sclerosis (ALS) patients and is located in the OPTN binding domain. Quantitative mRNA expression and protein analysis in cerebellar tissue showed a striking reduction of OPTN and/or TBK1 expression in 4 out of 5 patients supporting pathogenicity in these specific patients and suggesting a loss-of-function disease mechanism. Importantly, neuropathologic examination showed FTLD-TDP type A in the absence of motor neuron disease in 3 pathogenic mutation carriers. In conclusion, we highlight TBK1 as an important cause of pure FTLD-TDP, identify the first OPTN mutations in FTLD-TDP, and suggest a potential oligogenic basis for at least a subset of FTLD-TDP patients. Our data further add to the growing body of

  7. Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease

    PubMed Central

    Pottier, Cyril; Bieniek, Kevin F.; Finch, NiCole; van de Vorst, Maartje; Baker, Matt; Perkersen, Ralph; Brown, Patricia; Ravenscroft, Thomas; van Blitterswijk, Marka; Nicholson, Alexandra M.; DeTure, Michael; Knopman, David S.; Josephs, Keith A.; Parisi, Joseph E.; Petersen, Ronald; Boylan, Kevin B.; Boeve, Bradley F.; Graff-Radford, Neill R.; Veltman, Joris A.; Gilissen, Christian; Murray, Melissa; Dicksonand, Dennis W.; Rademakers, Rosa

    2015-01-01

    Frontotemporal lobar degeneration with TAR DNA binding protein 43 inclusions (FTLD-TDP) is the most common pathology associated with frontotemporal dementia (FTD). Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) and mutations in progranulin (GRN) are the major known genetic causes of FTLD-TDP; however, the genetic etiology in the majority of FTLD-TDP remains unexplained. In this study, we performed whole-genome sequencing in 104 pathologically confirmed FTLD-TDP patients from the Mayo Clinic brain bank negative for C9ORF72 and GRN mutations and report on the contribution of rare single nucleotide and copy-number variants in 21 known neurodegenerative disease genes. Interestingly, we identified 5 patients (4.8%) with variants in optineurin (OPTN) and TANK-binding kinase 1 (TBK1) that are predicted to be highly pathogenic, including two double mutants. Case A was a compound heterozygote for mutations in OPTN, carrying the p.Q235* nonsense and p.A481V missense mutation in trans, while case B carried a deletion of OPTN exons 13–15 (p.Gly538Glufs*27) and a loss-of-function mutation (p.Arg117*) in TBK1. Cases C–E carried heterozygous missense mutations in TBK1, including the p.Glu696Lys mutation which was previously reported in two amyotrophic lateral sclerosis (ALS) patients and is located in the OPTN binding domain. Quantitative mRNA expression and protein analysis in cerebellar tissue showed a striking reduction of OPTN and/or TBK1 expression in 4 out of 5 patients supporting pathogenicity in these specific patients and suggesting a loss-of-function disease mechanism. Importantly, neuropathologic examination showed FTLD-TDP type A in the absence of motor neuron disease in 3 pathogenic mutation carriers. In conclusion, we highlight TBK1 as an important cause of pure FTLD-TDP, identify the first OPTN mutations in FTLD-TDP, and suggest a potential oligogenic basis for at least a subset of FTLD-TDP patients. Our data further adds to the growing body

  8. ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3β in the signal network.

    PubMed

    Feng, L; Zhang, D; Fan, C; Ma, C; Yang, W; Meng, Y; Wu, W; Guan, S; Jiang, B; Yang, M; Liu, X; Guo, D

    2013-01-01

    HeLa cells treated with celastrol, a natural compound with inhibitive effect on proteasome, exhibited increase in apoptotic rate and characteristics of apoptosis. To clarify the signal network activated by celastrol to induce apoptosis, both the direct target proteins and undirect target proteins of celastrol were searched in the present study. Proteasome catalytic subunit β1 was predicted by computational analysis to be a possible direct target of celastrol and confirmed by checking direct effect of celastrol on the activity of recombinant human proteasome subunit β1 in vitro. Undirect target-related proteins of celastrol were searched using proteomic studies including two-dimensional electrophoresis (2-DE) analysis and iTRAQ-based LC-MS analysis. Possible target-related proteins of celastrol such as endoplasmic reticulum protein 29 (ERP29) and mitochondrial import receptor Tom22 (TOM22) were found by 2-DE analysis of total cellular protein expression profiles. Further study showed that celastrol induced ER stress and ER stress inhibitor could ameliorate cell death induced by celastrol. Celastrol induced translocation of Bax into the mitochondria, which might be related to the upregulation of BH-3-only proteins such as BIM and the increase in the expression level of TOM22. To further search possible target-related proteins of celastrol in ER and ER-related fractions, iTRAQ-based LC-MS method was use to analyze protein expression profiles of ER/microsomal vesicles-riched fraction of cells with or without celastrol treatment. Based on possible target-related proteins found in both 2-DE analysis and iTRAQ-based LC-MS analysis, protein-protein interaction (PPI) network was established using bioinformatic analysis. The important role of glycogen synthase kinase-3β (GSK3β) in the signal cascades of celastrol was suggested. Pretreatment of LiCL, an inhibitor of GSK3β, could significantly ameliorate apoptosis induced by celastrol. On the basis of the results of the

  9. Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence.

    PubMed

    Schoberle, Taylor J; Chung, Lawton K; McPhee, Joseph B; Bogin, Ben; Bliska, James B

    2016-04-01

    PathogenicYersiniaspecies utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promoteYersiniapathogenesis. In turn,Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior toYersinia pseudotuberculosisinfection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of aY. pseudotuberculosisyopMmutant was compared to that of ayopJ yopM,yopE yopM,yopH yopM,yopT yopM, orypkA yopMmutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1β (IL-1β), and pyroptosis in LPS-activated macrophages infected with wild-type or mutantY. pseudotuberculosisstrains. Results show enhanced activation of caspase-1 after infection with theyopJ yopMmutant relative to infection by any other single or double mutant. Similar results were obtained with theyopJ,yopM, andyopJ yopMmutants ofYersinia pestis Following intravenous infection of mice, theY. pseudotuberculosisyopJmutant was as virulent as the wild type, while theyopJ yopMmutant was significantly more attenuated than theyopMmutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promotingYersiniavirulence. PMID:26810037

  10. Miniature Inverted–Repeat Transposable Elements (MITEs) Have Been Accumulated through Amplification Bursts and Play Important Roles in Gene Expression and Species Diversity in Oryza sativa

    PubMed Central

    Lu, Chen; Chen, Jiongjiong; Zhang, Yu; Hu, Qun; Su, Wenqing; Kuang, Hanhui

    2012-01-01

    Miniature inverted–repeat transposable elements (MITEs) are predicted to play important roles on genome evolution. We developed a BLASTN-based approach for de novo identification of MITEs and systematically analyzed MITEs in rice genome. The genome of rice cultivar Nipponbare (Oryza sativa ssp. japonica) harbors 178,533 MITE-related sequences classified into 338 families. Pairwise nucleotide diversity and phylogenetic tree analysis indicated that individual MITE families were resulted from one or multiple rounds of amplification bursts. The timing of amplification burst varied considerably between different MITE families or subfamilies. MITEs are associated with 23,623 (58.2%) genes in rice genome. At least 7,887 MITEs are transcribed and more than 3,463 were transcribed with rice genes. The MITE sequences transcribed with rice coding genes form 1,130 pairs of potential natural sense/antisense transcripts. MITEs generate 23.5% (183,837 of 781,885) of all small RNAs identified from rice. Some MITE families generated small RNAs mainly from the terminals, while other families generated small RNAs predominantly from the central region. More than half (51.8%) of the MITE-derived small RNAs were generated exclusively by MITEs located away from genes. Genome-wide analysis showed that genes associated with MITEs have significantly lower expression than genes away from MITEs. Approximately 14.8% of loci with full-length MITEs have presence/absence polymorphism between rice cultivars 93-11 (O. sativa ssp. indica) and Nipponbare. Considering that different sets of genes may be regulated by MITE-derived small RNAs in different genotypes, MITEs provide considerable diversity for O. sativa. PMID:22096216

  11. Complement factor B is the downstream effector of TLRs and plays an important role in a mouse model of severe sepsis.

    PubMed

    Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M; Wu, Xiaobo; Atkinson, John P; Chao, Wei

    2013-12-01

    Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of TLRs mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. In this article, we show that activation of TLR2, TLR3, and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture in a mouse model, augmented cfB levels in the serum, peritoneal cavity, and major organs including the kidney and heart. Cecal ligation and puncture also led to the alternative pathway activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum alternative pathway via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 upregulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production, and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

  12. A novel formaldehyde metabolic pathway plays an important role during formaldehyde metabolism and detoxification in tobacco leaves under liquid formaldehyde stress.

    PubMed

    Wang, Ru; Zeng, Zhidong; Liu, Ting; Liu, Ang; Zhao, Yan; Li, Kunzhi; Chen, Limei

    2016-08-01

    Tobacco and Arabidopsis are two model plants often used in botany research. Our previous study indicated that the formaldehyde (HCHO) uptake and assimilation capacities of tobacco leaves were weaker than those of Arabidopsis leaves. After treatment with a 2, 4 or 6 mM HCHO solution for 24 h, detached tobacco leaves absorbed approximately 40% of the HCHO from the treatment solution. (13)C-NMR analysis detected a novel HCHO metabolic pathway in 2 mM H(13)CHO-treated tobacco leaves. [4-(13)C]Asn, [3-(13)C]Gln and [U-(13)C]oxalic acid (OA) were produced from this pathway after H(13)COOH generation during H(13)CHO metabolism in tobacco leaves. Pretreatments of cyclosporin A (CSA) and dark almost completely inhibited the generation of [4-(13)C]Asn, [3-(13)C]Gln and [U-(13)C]OA from this pathway but did not suppressed the production of H(13)COOH in 2 mM H(13)CHO-treated tobacco leaves. The evidence suggests that this novel pathway has an important role during the metabolic detoxification of HCHO in tobacco leaves. The analysis of the chlorophyll and Rubisco contents indicated that CSA and dark pretreatments did not severely affect the survival of leaf cells but significantly inhibited the HCHO uptake by tobacco leaves. Based on the effects of CSA and dark pretreatments on HCHO uptake and metabolism, it is estimated that the contribution of this novel metabolic pathway to HCHO uptake is approximately 60%. The data obtained from the (13)C-NMR analysis revealed the mechanism underlying the weaker HCHO uptake and assimilation of tobacco leaves compared to Arabidopsis leaves. PMID:27116371

  13. Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy

    SciTech Connect

    He, Shu-Lan; Tan, Wu-Hong; Zhang, Zeng-Tie; Zhang, Feng; Qu, Cheng-Juan; Lei, Yan-Xia; Zhu, Yan-He; Yu, Han-Jie; Xiang, You-Zhang; and others

    2013-10-15

    Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios≥2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD. Highlights: • Thirty-four up-regulated genes were detected in KD versus health controls. • Forty pathways and four networks were detected in KD. • PGC-1alpha regulated energy metabolism and anti-apoptosis in KD.

  14. Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

    PubMed Central

    Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

    2013-01-01

    Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

  15. Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

    PubMed Central

    2011-01-01

    Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

  16. What Role for Law, Human Rights, and Bioethics in an Age of Big Data, Consortia Science, and Consortia Ethics? The Importance of Trustworthiness

    PubMed Central

    Dove, Edward S.; Özdemir, Vural

    2015-01-01

    The global bioeconomy is generating new paradigm-shifting practices of knowledge co-production, such as collective innovation; large-scale, data-driven global consortia science (Big Science); and consortia ethics (Big Ethics). These bioeconomic and sociotechnical practices can be forces for progressive social change, but they can also raise predicaments at the interface of law, human rights, and bioethics. In this article, we examine one such double-edged practice: the growing, multivariate exploitation of Big Data in the health sector, particularly by the private sector. Commercial exploitation of health data for knowledge-based products is a key aspect of the bioeconomy and is also a topic of concern among publics around the world. It is exacerbated in the current age of globally interconnected consortia science and consortia ethics, which is characterized by accumulating epistemic proximity, diminished academic independence, “extreme centrism”, and conflicted/competing interests among innovation actors. Extreme centrism is of particular importance as a new ideology emerging from consortia science and consortia ethics; this relates to invariably taking a middle-of-the-road populist stance, even in the event of human rights breaches, so as to sustain the populist support needed for consortia building and collective innovation. What role do law, human rights, and bioethics—separate and together—have to play in addressing these predicaments and opportunities in early 21st century science and society? One answer we propose is an intertwined ethico-legal normative construct, namely trustworthiness. By considering trustworthiness as a central pillar at the intersection of law, human rights, and bioethics, we enable others to trust us, which in turns allows different actors (both nonprofit and for-profit) to operate more justly in consortia science and ethics, as well as to access and responsibly use health data for public benefit. PMID:26345196

  17. Role of different additives and metallic micro minerals on the enhanced citric acid production by Aspergillus niger MNNG-115 using different carbohydrate materials.

    PubMed

    Ali, Sikander; Haq, Ikram-ul

    2005-01-01

    The present investigation deals with the promotry effect of different additives and metallic micro minerals on citric acid production by Aspergillus niger MNNG-115 using different carbohydrate materials. For this, sugar cane bagasse was fortified with sucrose salt medium. Ethanol and coconut oil at 3.0% (v/w) level increased citric acid productivity. Fluoroacetate at a concentration of 1.0 mg/ml bagasse enhanced the yield of citric acid significantly. However, the addition of ethanol and fluoroacetate after 6 h of growth gave the maximum conversion of available sugar to citric acid. In another study, influence of some metallic micro-minerals viz. copper sulphate, molybdenum sulphate, zinc sulphate and cobalt sulphate on microbial synthesis of citric acid using molasses medium was also carried out. It was found that copper sulphate and molybdenum sulphate remarkably enhanced the production of citric acid while zinc sulphate was not so effective. However, cobalt sulphate was the least effective for microbial biosynthesis of citric acid under the same experimental conditions. In case of CuSO(4), the strain of Aspergillus niger MNNG-115 showed enhanced citric productivity with experimental (9.80%) over the control (7.54%). In addition, the specific productivity of the culture at 30 ppm CuSO(4) (Q(p) = 0.012a g/g cells/h) was several folds higher than other all other concentrations. All kinetic parameters including yield coefficients and volumetric rates revealed the hyper productivity of citric acid by CuSO(4) using blackstrap molasses as the basal carbon source. PMID:15678560

  18. Role of enzymatic activity in muscle damage and cytotoxicity induced by Bothrops asper Asp49 phospholipase A2 myotoxins: are there additional effector mechanisms involved?

    PubMed Central

    Mora-Obando, Diana; Díaz, Cecilia; Angulo, Yamileth; Gutiérrez, José María

    2014-01-01

    Viperid venoms often contain mixtures of Asp49 and Lys49 PLA2 myotoxin isoforms, relevant to development of myonecrosis. Given their difference in catalytic activity, mechanistic studies on each type require highly purified samples. Studies on Asp49 PLA2s have shown that enzyme inactivation using p-bromophenacyl bromide (p-BPB) drastically affects toxicity. However, based on the variable levels of residual toxicity observed in some studies, it has been suggested that effector mechanisms independent of catalysis may additionally be involved in the toxicity of these enzymes, possibly resembling those of the enzymatically inactive Lys49 myotoxins. A possibility that Lys49 isoforms could be present in Asp49 PLA2 preparations exists and, if undetected in previous studies, could explain the variable residual toxicity. This question is here addressed by using an enzyme preparation ascertained to be free of Lys49 myotoxins. In agreement with previous reports, inactivation of the catalytic activity of an Asp49 myotoxin preparation led to major inhibition of toxic effects in vitro and in vivo. The very low residual levels of myotoxicity (7%) and cytotoxicity (4%) observed can be attributed to the low, although detectable, enzyme remaining active after p-BPB treatment (2.7%), and would be difficult to reconcile with the proposed existence of additional catalytic-independent toxic mechanisms. These findings favor the concept that the effector mechanism of toxicity of Asp49 PLA2 myotoxins from viperids fundamentally relies on their ability to hydrolyze phospholipids, arguing against the proposal that membrane disruption may also be caused by additional mechanisms that are independent of catalysis. PMID:25276503

  19. The role of an aromatic group in remote chiral induction during conjugate addition of α-sulfonylallylic carbanions to ethyl crotonate

    PubMed Central

    Levinger, Shlomo; Nair, Ranjeet

    2008-01-01

    Summary The impact of a remote aromatic nucleus on the stereochemical outcome of the conjugate addition of α-sulfonylallylic carbanions to an α,β-unsaturated ester was investigated. α-Regioselectivity coupled with anti-diastereoselectivity is accompanied by a prominent preference for relative configuration 3 over 4. The 9-anthryl moiety has shown itself greatly superior over all other groups in this bias. A lithium ion–aromatic π interaction has been postulated as decisive for the remote transmission of chirality. PMID:18941617

  20. 1,4-Addition of Lithium Diisopropylamide to Unsaturated Esters: Role of Rate-Limiting Deaggregation, Autocatalysis, Lithium Chloride Catalysis and Other Mixed Aggregation Effects

    PubMed Central

    Ma, Yun; Hoepker, Alexander C.; Gupta, Lekha; Faggin, Marc F.; Collum, David B.

    2010-01-01

    Lithium diisopropylamide (LDA) in tetrahydrofuran at −78 °C undergoes 1,4-addition to an unsaturated ester via a rate-limiting deaggregation of LDA dimer followed by a post-rate-limiting reaction with the substrate. Muted autocatalysis is traced to a lithium enolate-mediated deaggregation of the LDA dimer and the intervention of LDA-lithium enolate mixed aggregates displaying higher reactivities than LDA. Striking accelerations are elicited by <1.0 mol % LiCl. Rate and mechanistic studies reveal that the uncatalyzed and catalyzed pathways funnel through a common monosolvated-monomer-based intermediate. Four distinct classes of mixed aggregation effects are discussed. PMID:20961095

  1. Attosecond pulse carrier-envelope phase effects on ionized electron momentum and energy distributions: roles of frequency, intensity and an additional IR pulse

    NASA Astrophysics Data System (ADS)

    Peng, Liang-You; Pronin, Evgeny A.; Starace, Anthony F.

    2008-02-01

    The effects of the carrier-envelope phase (CEP) of a few-cycle attosecond pulse on ionized electron momentum and energy spectra are analyzed, both with and without an additional few-cycle IR pulse. In the absence of an IR pulse, the CEP-induced asymmetries in the ionized electron momentum distributions are shown to vary as the 3/2 power of the attosecond pulse intensity. These asymmetries are also found to satisfy an approximate scaling law involving the frequency and intensity of the attosecond pulse. In the presence of even a very weak IR pulse (having an intensity of the order of 1011 1012 W cm-2), the attosecond pulse CEP-induced asymmetries in the ionized electron momentum distributions are found to be significantly augmented. In addition, for higher IR laser intensities, we observe for low electron energies peaks separated by the IR photon energy in one electron momentum direction along the laser polarization axis; in the opposite direction, we find structured peaks that are spaced by twice the IR photon energy. Possible physical mechanisms for such asymmetric, low-energy structures in the ionized electron momentum distribution are proposed. Our results are based on single-active-electron solutions of the three-dimensional, time-dependent Schrödinger equation including atomic potentials appropriate for the H and He atoms.

  2. Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells.

    PubMed Central

    Bassuk, A G; Anandappa, R T; Leiden, J M

    1997-01-01

    The transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors. Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2), suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution. Despite these findings, the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown. In the studies described in this report, we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells. This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins. In addition, the Ets-NF-kappaB/NFAT interaction requires the presence of DNA binding sites for both proteins, as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins. A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB (p50 + p65) and Ets-1, suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers. Taken together, these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses. These interactions represent a potential target

  3. Heat tolerance plays an important role in regulating remontant flowering in an F1 population of octoploid strawberry (Fragaria ×ananassa)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Flower initiation in strawberry is often classified by photoperiod sensitivity; however, temperature also plays a major role in determining flower initiation. OBJECTIVE: Our goal was to determine the role heat tolerance plays in regulating remontant flowering in a segregating population ...

  4. Small RNA and degradome deep sequencing reveals drought-and tissue-specific micrornas and their important roles in drought-sensitive and drought-tolerant tomato genotypes.

    PubMed

    Candar-Cakir, Bilgin; Arican, Ercan; Zhang, Baohong

    2016-08-01

    Drought stress has adverse impacts on plant production and productivity. MicroRNAs (miRNAs) are one class of noncoding RNAs regulating gene expression post-transcriptionally. In this study, we employed small RNA and degradome sequencing to systematically investigate the tissue-specific miRNAs responsible to drought stress, which are understudied in tomato. For this purpose, root and upground tissues of two different drought-responsive tomato genotypes (Lycopersicon esculentum as sensitive and L. esculentum var. cerasiforme as tolerant) were subjected to stress with 5% polyethylene glycol for 7 days. A total of 699 conserved miRNAs belonging to 578 families were determined and 688 miRNAs were significantly differentially expressed between different treatments, tissues and genotypes. Using degradome sequencing, 44 target genes were identified associated with 36 miRNA families. Drought-related miRNAs and their targets were enriched functionally by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Totally, 53 miRNAs targeted 23 key drought stress- and tissue development-related genes, including DRP (dehydration-responsive protein), GTs (glycosyltransferases), ERF (ethylene responsive factor), PSII (photosystem II) protein, HD-ZIP (homeodomain-leucine zipper), MYB and NAC-domain transcription factors. miR160, miR165, miR166, miR171, miR398, miR408, miR827, miR9472, miR9476 and miR9552 were the key miRNAs functioning in regulation of these genes and involving in tomato response to drought stress. Additionally, plant hormone signal transduction pathway genes were differentially regulated by miR169, miR172, miR393, miR5641, miR5658 and miR7997 in both tissues of both sensitive and tolerant genotypes. These results provide new insight into the regulatory role of miRNAs in drought response with plant hormone signal transduction and drought-tolerant tomato breeding. PMID:26857916

  5. Age plays an important role in the relationship between smoking status and obesity risk: a large scale cross-sectional study of Chinese adults

    PubMed Central

    Su, Pu; Hong, Liu; Sun, Hang; Zhao, Yi Fan; Li, Liang

    2015-01-01

    Objective: To study the role of age plays in the relationship between smoking status and obesity in both Chinese men and women. Methods: From Chinese Physical and Psychological Database, participants were divided into non-smokers, current smokers, and former smokers. Body mass index (BMI), waist circumference (WC), fat percentage, fat mass, and fat free mass were measured. The mean, standard deviation and frequency of these indicators were calculated for each age bracket. One-way ANOVA and post-hoc test analyses were used to detect the difference among these three groups. Results: In men, from 19 to 24 years old, BMI, WC and fat free mass of current smokers were higher than that of non-smokers (P<0.01). However, fat mass and fat percentage of current smokers were lower than that of non-smokers but higher than that of former smokers (P<0.01). From 25 to 34 years old, BMI and fat mass of former smokers were higher than non-smokers and current smokers (P<0.01). In addition, WC and fat free mass of non-smokers were lower than that of current smokers and former smokers (P<0.01). From 45 to older, BMI, WC, fat mass, fat free mass and fat percentage of former smokers were higher than that of current smokers (P<0.01). From 55 to older, BMI, WC, fat mass, fat free mass and fat percentage of current smokers were lower than that of non-smokers (P<0.01). In women, smoking status might not be significantly related to obesity (P>0.05). Conclusion: For young men, smoking might have an effect on increasing fat free mass, BMI and WC, and decreasing fat mass and fat percentage. For middle and older men, smoking might have an effect on decreasing fat free mass, fat mass, BMI, WC, and fat percentage. Obesity risk should be paid more attention in smoking cessation programs for those former smokers. PMID:26770514

  6. EXPERIMENTAL EVIDENCE FOR THE FORMATION OF HIGHLY SUPERHYDROGENATED POLYCYCLIC AROMATIC HYDROCARBONS THROUGH H ATOM ADDITION AND THEIR CATALYTIC ROLE IN H{sub 2} FORMATION

    SciTech Connect

    Thrower, J. D.; Jorgensen, B.; Friis, E. E.; Baouche, S.; Luntz, A. C.; Andersen, M.; Hammer, B.; Hornekaer, L.; Mennella, V.

    2012-06-10

    Mass spectrometry measurements show the formation of highly superhydrogenated derivatives of the polycyclic aromatic hydrocarbon molecule coronene through H atom addition reactions. The observed product mass distribution provides evidence also for abstraction reactions resulting in H{sub 2} formation, in agreement with recent IR measurements. Complementary density functional theory calculations confirm the stability of the observed superhydrogenated species toward spontaneous H and H{sub 2} loss indicating that abstraction reactions may be the dominant route to H{sub 2} formation involving neutral polycyclic aromatic hydrocarbons (PAHs). The results indicate that highly superhydrogenated PAHs could well be formed and could act as efficient catalysts for H{sub 2} formation in the interstellar medium in low UV flux regions.

  7. Utilizing Peer Mentor Roles in Learning Communities

    ERIC Educational Resources Information Center

    Rieske, Laura Jo; Benjamin, Mimi

    2015-01-01

    For a number of learning community programs, peer mentors provide an additional layer of staffing support. This chapter highlights peer mentor roles from a sample of programs and suggests important components for the construction of these roles.

  8. Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

    PubMed Central

    García-Herrero, Carmen-María; Rubio-Cabezas, Oscar; Azriel, Sharona; Gutierrez-Nogués, Angel; Aragonés, Angel; Vincent, Olivier; Campos-Barros, Angel; Argente, Jesús; Navas, María-Angeles

    2012-01-01

    Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing. PMID:22291974

  9. Sirtuin 3, a New Target of PGC-1α, Plays an Important Role in the Suppression of ROS and Mitochondrial Biogenesis

    PubMed Central

    Kong, Xingxing; Wang, Rui; Xue, Yuan; Liu, Xiaojun; Zhang, Huabing; Chen, Yong; Fang, Fude; Chang, Yongsheng

    2010-01-01

    Background Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1α induces several key reactive oxygen species (ROS)-detoxifying enzymes, but the molecular mechanism underlying this is not well understood. Results Here we show that PGC-1α strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. Knockdown of PGC-1α led to decreased Sirt3 gene expression. PGC-1α activated the mouse SIRT3 promoter, which was mediated by an estrogen-related receptor (ERR) binding element (ERRE) (−407/−399) mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that ERRα bound to the identified ERRE and PGC-1α co-localized with ERRα in the mSirt3 promoter. Knockdown of ERRα reduced the induction of Sirt3 by PGC-1α in C2C12 myotubes. Furthermore, Sirt3 was essential for PGC-1α-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. Overexpression of SIRT3 or PGC-1α in C2C12 myotubes decreased basal ROS level. In contrast, knockdown of mSIRT3 increased basal ROS level and blocked the inhibitory effect of PGC-1α on cellular ROS production. Finally, SIRT3 stimulated mitochondrial biogenesis, and SIRT3 knockdown decreased the stimulatory effect of PGC-1α on mitochondrial biogenesis in C2C12 myotubes. Conclusion Our results indicate that Sirt3 functions as a downstream target gene of PGC-1α and mediates the PGC-1α effects on cellular ROS production and mitochondrial biogenesis. Thus, SIRT3 integrates cellular energy metabolism and ROS generation. The

  10. The Arabidopsis thylakoid ADP/ATP carrier TAAC has an additional role in supplying plastidic phosphoadenosine 5'-phosphosulfate to the cytosol.

    PubMed

    Gigolashvili, Tamara; Geier, Melanie; Ashykhmina, Natallia; Frerigmann, Henning; Wulfert, Sabine; Krueger, Stephan; Mugford, Sarah G; Kopriva, Stanislav; Haferkamp, Ilka; Flügge, Ulf-Ingo

    2012-10-01

    3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the high-energy sulfate donor for sulfation reactions. Plants produce some PAPS in the cytosol, but it is predominantly produced in plastids. Accordingly, PAPS has to be provided by plastids to serve as a substrate for sulfotransferase reactions in the cytosol and the Golgi apparatus. We present several lines of evidence that the recently described Arabidopsis thaliana thylakoid ADP/ATP carrier TAAC transports PAPS across the plastid envelope and thus fulfills an additional function of high physiological relevance. Transport studies using the recombinant protein revealed that it favors PAPS, 3'-phosphoadenosine 5'-phosphate, and ATP as substrates; thus, we named it PAPST1. The protein could be detected both in the plastid envelope membrane and in thylakoids, and it is present in plastids of autotrophic and heterotrophic tissues. TAAC/PAPST1 belongs to the mitochondrial carrier family in contrast with the known animal PAPS transporters, which are members of the nucleotide-sugar transporter family. The expression of the PAPST1 gene is regulated by the same MYB transcription factors also regulating the biosynthesis of sulfated secondary metabolites, glucosinolates. Molecular and physiological analyses of papst1 mutant plants indicate that PAPST1 is involved in several aspects of sulfur metabolism, including the biosynthesis of thiols, glucosinolates, and phytosulfokines. PMID:23085732

  11. The Arabidopsis Thylakoid ADP/ATP Carrier TAAC Has an Additional Role in Supplying Plastidic Phosphoadenosine 5′-Phosphosulfate to the Cytosol[W

    PubMed Central

    Gigolashvili, Tamara; Geier, Melanie; Ashykhmina, Natallia; Frerigmann, Henning; Wulfert, Sabine; Krueger, Stephan; Mugford, Sarah G.; Kopriva, Stanislav; Haferkamp, Ilka; Flügge, Ulf-Ingo

    2012-01-01

    3′-Phosphoadenosine 5′-phosphosulfate (PAPS) is the high-energy sulfate donor for sulfation reactions. Plants produce some PAPS in the cytosol, but it is predominantly produced in plastids. Accordingly, PAPS has to be provided by plastids to serve as a substrate for sulfotransferase reactions in the cytosol and the Golgi apparatus. We present several lines of evidence that the recently described Arabidopsis thaliana thylakoid ADP/ATP carrier TAAC transports PAPS across the plastid envelope and thus fulfills an additional function of high physiological relevance. Transport studies using the recombinant protein revealed that it favors PAPS, 3′-phosphoadenosine 5′-phosphate, and ATP as substrates; thus, we named it PAPST1. The protein could be detected both in the plastid envelope membrane and in thylakoids, and it is present in plastids of autotrophic and heterotrophic tissues. TAAC/PAPST1 belongs to the mitochondrial carrier family in contrast with the known animal PAPS transporters, which are members of the nucleotide-sugar transporter family. The expression of the PAPST1 gene is regulated by the same MYB transcription factors also regulating the biosynthesis of sulfated secondary metabolites, glucosinolates. Molecular and physiological analyses of papst1 mutant plants indicate that PAPST1 is involved in several aspects of sulfur metabolism, including the biosynthesis of thiols, glucosinolates, and phytosulfokines. PMID:23085732

  12. Improving nutrient management practices in agriculture: The role of risk-based beliefs in understanding farmers' attitudes toward taking additional action

    NASA Astrophysics Data System (ADS)

    Wilson, Robyn S.; Howard, Gregory; Burnett, Elizabeth A.

    2014-08-01

    A recent increase in the amount of dissolved reactive phosphorus (DRP) entering the western Lake Erie basin is likely due to increased spring storm events in combination with issues related to fertilizer application and timing. These factors in combination with warmer lake temperatures have amplified the spread of toxic algal blooms. We assessed the attitudes of farmers in northwest Ohio toward taking at least one additional action to reduce nutrient loss on their farm. Specifically, we (1) identified to what extent farm and farmer characteristics (e.g., age, gross farm sales) as well as risk-based beliefs (e.g., efficacy, risk perception) influenced attitudes, and (2) assessed how these characteristics and beliefs differ in their predictive ability based on unobservable latent classes of farmers. Risk perception, or a belief that negative impacts to profit and water quality from nutrient loss were likely, was the most consistent predictor of farmer attitudes. Response efficacy, or a belief that taking action on one's farm made a difference, was found to significantly influence attitudes, although this belief was particularly salient for the minority class of farmers who were older and more motivated by profit. Communication efforts should focus on the negative impacts of nutrient loss to both the farm (i.e., profit) and the natural environment (i.e., water quality) to raise individual perceived risk among the majority, while the minority need higher perceived efficacy or more specific information about the economic effectiveness of particular recommended practices.

  13. Thermal evolution behavior and fluid dynamics during laser additive manufacturing of Al-based nanocomposites: Underlying role of reinforcement weight fraction

    NASA Astrophysics Data System (ADS)

    Gu, Dongdong; Yuan, Pengpeng

    2015-12-01

    In this study, a three-dimensional transient computational fluid dynamics model was established to investigate the influence of reinforcement weight fraction on thermal evolution behavior and fluid dynamics during selective laser melting (SLM) additive manufacturing of TiC/AlSi10Mg nanocomposites. The powder-to-solid transition and nonlinear variation of thermal physical properties of as-used materials were considered in the numerical model, using the Gaussian distributed volumetric heat source. The simulation results showed that the increase of operating temperature and the resultant formation of larger melt pool were caused by the increase of weight fraction of reinforcement. The Marangoni convection was intensified using a larger reinforcement content, accelerating the coupled motion of fluid and solid particles. The circular flows appeared when the TiC content reached 5.0 wt. % and the larger-sized circular flows were present as the reinforcement content increased to 7.5 wt. %. The experimental study on surface morphologies and microstructures on the polished sections of SLM-processed TiC/AlSi10Mg nanocomposite parts was performed. A considerably dense and smooth surface free of any balling effect and pore formation was obtained when the reinforcement content was optimized at 5.0 wt. %, due to the sufficient liquid formation and moderate Marangoni flow. Novel ring-structured reinforcing particulates were tailored because of the combined action of the attractive effect of centripetal force and repulsive force, which was consistent with the simulation results.

  14. Associations between Work Environment and Psychological Distress after a Workplace Terror Attack: The Importance of Role Expectations, Predictability and Leader Support

    PubMed Central

    Birkeland, Marianne Skogbrott; Nielsen, Morten Birkeland; Knardahl, Stein; Heir, Trond

    2015-01-01

    Experiencing terrorism is associated with high levels of psychological distress among survivors. The aim of the present study was to examine whether work environmental factors such as role clarity and predictability, role conflicts, and leader support may protect against elevated levels of psychological distress after a workplace terrorist attack. Data from approximately 1800 ministerial employees were collected ten months after the 2011 Oslo bombing attack which targeted the Norwegian ministries. The results show that after a traumatic event, lower role conflicts, higher role clarity, higher predictability, and higher leader support were independently associated with lower psychological distress. These findings suggest that the workplace environment may be a facilitator of employees’ mental health after stressful events. PMID:25769023

  15. A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors

    PubMed Central

    Tilgner, K; Neganova, I; Moreno-Gimeno, I; AL-Aama, J Y; Burks, D; Yung, S; Singhapol, C; Saretzki, G; Evans, J; Gorbunova, V; Gennery, A; Przyborski, S; Stojkovic, M; Armstrong, L; Jeggo, P; Lako, M

    2013-01-01

    DNA double strand breaks (DSBs) are the most common form of DNA damage and are repaired by non-homologous-end-joining (NHEJ) or homologous recombination (HR). Several protein components function in NHEJ, and of these, DNA Ligase IV is essential for performing the final ‘end-joining' step. Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, increased predisposition to leukaemia and variable degrees of immunodeficiency. In this manuscript, we report the creation of a human induced pluripotent stem cell (iPSC) model of LIG4 deficiency, which accurately replicates the DSB repair phenotype of LIG4 patients. Our findings demonstrate that impairment of NHEJ-mediated-DSB repair in human iPSC results in accumulation of DSBs and enhanced apoptosis, thus providing new insights into likely mechanisms used by pluripotent stem cells to maintain their genomic integrity. Defects in NHEJ-mediated-DSB repair also led to a significant decrease in reprogramming efficiency of human cells and accumulation of chromosomal abnormalities, suggesting a key role for NHEJ in somatic cell reprogramming and providing insights for future cell based therapies for applications of LIG4-iPSCs. Although haematopoietic specification of LIG4-iPSC is not affected per se, the emerging haematopoietic progenitors show a high accumulation of DSBs and enhanced apoptosis, resulting in reduced numbers of mature haematopoietic cells. Together our findings provide new insights into the role of NHEJ-mediated-DSB repair in the survival and differentiation of progenitor cells, which likely underlies the developmental abnormalities observed in many DNA damage disorders. In addition, our findings are important for understanding how genomic instability arises in pluripotent stem cells and for defining appropriate culture conditions that restrict DNA damage and result in ex vivo expansion of stem cells with intact genomes. PMID

  16. A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors.

    PubMed

    Tilgner, K; Neganova, I; Moreno-Gimeno, I; Al-Aama, J Y; Burks, D; Yung, S; Singhapol, C; Saretzki, G; Evans, J; Gorbunova, V; Gennery, A; Przyborski, S; Stojkovic, M; Armstrong, L; Jeggo, P; Lako, M

    2013-08-01

    DNA double strand breaks (DSBs) are the most common form of DNA damage and are repaired by non-homologous-end-joining (NHEJ) or homologous recombination (HR). Several protein components function in NHEJ, and of these, DNA Ligase IV is essential for performing the final 'end-joining' step. Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, increased predisposition to leukaemia and variable degrees of immunodeficiency. In this manuscript, we report the creation of a human induced pluripotent stem cell (iPSC) model of LIG4 deficiency, which accurately replicates the DSB repair phenotype of LIG4 patients. Our findings demonstrate that impairment of NHEJ-mediated-DSB repair in human iPSC results in accumulation of DSBs and enhanced apoptosis, thus providing new insights into likely mechanisms used by pluripotent stem cells to maintain their genomic integrity. Defects in NHEJ-mediated-DSB repair also led to a significant decrease in reprogramming efficiency of human cells and accumulation of chromosomal abnormalities, suggesting a key role for NHEJ in somatic cell reprogramming and providing insights for future cell based therapies for applications of LIG4-iPSCs. Although haematopoietic specification of LIG4-iPSC is not affected per se, the emerging haematopoietic progenitors show a high accumulation of DSBs and enhanced apoptosis, resulting in reduced numbers of mature haematopoietic cells. Together our findings provide new insights into the role of NHEJ-mediated-DSB repair in the survival and differentiation of progenitor cells, which likely underlies the developmental abnormalities observed in many DNA damage disorders. In addition, our findings are important for understanding how genomic instability arises in pluripotent stem cells and for defining appropriate culture conditions that restrict DNA damage and result in ex vivo expansion of stem cells with intact genomes. PMID

  17. The role of additional computed tomography in the decision-making process on the secondary prevention in patients after systemic cerebral thrombolysis

    PubMed Central

    Sobolewski, Piotr; Kozera, Grzegorz; Szczuchniak, Wiktor; Nyka, Walenty M

    2016-01-01

    Introduction Patients with ischemic stroke undergoing intravenous (iv)-thrombolysis are routinely controlled with computed tomography on the second day to assess stroke evolution and hemorrhagic transformation (HT). However, the benefits of an additional computed tomography (aCT) performed over the next days after iv-thrombolysis have not been determined. Methods We retrospectively screened 287 Caucasian patients with ischemic stroke who were consecutively treated with iv-thrombolysis from 2008 to 2012. The results of computed tomography performed on the second (control computed tomography) and seventh (aCT) day after iv-thrombolysis were compared in 274 patients (95.5%); 13 subjects (4.5%), who died before the seventh day from admission were excluded from the analysis. Results aCTs revealed a higher incidence of HT than control computed tomographies (14.2% vs 6.6%; P=0.003). Patients with HT in aCT showed higher median of National Institutes of Health Stroke Scale score on admission than those without HT (13.0 vs 10.0; P=0.01) and higher presence of ischemic changes >1/3 middle cerebral artery territory (66.7% vs 35.2%; P<0.01). Correlations between presence of HT in aCT and National Institutes of Health Stroke Scale score on admission (rpbi 0.15; P<0.01), and the ischemic changes >1/3 middle cerebral artery (phi=0.03) existed, and the presence of HT in aCT was associated with 3-month mortality (phi=0.03). Conclusion aCT after iv-thrombolysis enables higher detection of HT, which is related to higher 3-month mortality. Thus, patients with severe middle cerebral artery infarction may benefit from aCT in the decision-making process on the secondary prophylaxis. PMID:26730196

  18. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge

    PubMed Central

    Singh, Balraj; Kinne, Hannah E.; Milligan, Ryan D.; Washburn, Laura J.; Olsen, Mark; Lucci, Anthony

    2016-01-01

    We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and

  19. The important tumor suppressor role of PER1 in regulating the cyclin–CDK–CKI network in SCC15 human oral squamous cell carcinoma cells

    PubMed Central

    Fu, Xiao-Juan; Li, Han-Xue; Yang, Kai; Chen, Dan; Tang, Hong

    2016-01-01

    Background Accumulating evidence suggests that the abnormal expression of the circadian clock gene PER1 is closely related to the development and progression of cancer. However, the exact molecular mechanism by which the abnormal expression of PER1 induces carcinogenesis is unclear. This study was conducted to investigate the alterations in downstream cell cycle genes, cell cycle distribution, cell proliferation, apoptosis, and in vivo tumorigenicity in SCC15 oral squamous cell carcinoma cells after PER1 downregulation. Materials and methods A stable SCC15 cell line was established to constitutively express shRNA targeting PER1. Quantitative real-time polymerase chain reaction (PCR) and Western blot analyses were conducted to estimate PER1 mRNA and protein expression. The expression of PER1, P53, CyclinD1, CyclinE, CyclinA2, CyclinB1, cyclin-dependent kinase (CDK) 1, CDK2, CDK4, CDK6, P16, P21, WEE1, and CDC25 mRNA was detected by quantitative real-time PCR. Cell cycle distribution, cell proliferation, and apoptosis were determined by flow cytometry. The in vivo tumorigenicity of SCC15 cells was evaluated in female BALB/c nu/nu mice. Results PER1 downregulation resulted in significantly increased mRNA expression levels of CyclinD1, CyclinE, CyclinB1, CDK1, and WEE1 (P<0.05), and significantly decreased mRNA expression levels of P53, CyclinA2, P16, P21, and CDC25 (P<0.05) compared to control cells. Additionally, PER1 downregulation led to significantly fewer cells in S phase (P<0.05), but significantly more cells in G2/M phase (P<0.05) compared to the control group. After PER1 downregulation, the cell proliferation index was significantly higher (P<0.05), and the apoptotic index was significantly lower (P<0.05). The in vivo tumorigenicity of SCC15 cells was significantly enhanced by PER1 downregulation (P<0.05). Conclusion PER1 is an important tumor suppressor gene which acts by regulating the Cyclin-CDK-cyclin-dependent kinase inhibitor regulatory network. An in

  20. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge.

    PubMed

    Singh, Balraj; Kinne, Hannah E; Milligan, Ryan D; Washburn, Laura J; Olsen, Mark; Lucci, Anthony

    2016-01-01

    We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and

  1. Immunodominant epitopes in nsp2 of porcine reproductive and respiratory syndrome virus are dispensable for replication but play an important role in viral pathogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) is the largest protein of the virus. Besides its crucial role in viral replication, recent studies indicated its involvement in modulating host immunity. In this study, each of the six identified immu...

  2. The importance of autonomy support and the mediating role of work motivation for well-being: testing self-determination theory in a Chinese work organisation.

    PubMed

    Nie, Youyan; Chua, Bee Leng; Yeung, Alexander Seeshing; Ryan, Richard M; Chan, Wai Yen

    2015-08-01

    We examine relations between perceived organisational autonomy support and different types of work motivation and well-being outcomes in 266 teachers from two government schools in China. We hypothesised that greater autonomy support would be associated with more autonomous forms of employee motivation, and that teacher motivation would in turn mediate the effects of autonomy support on indicators of work well-being (i.e., job satisfaction, work stress and physical ill symptoms). Results generally supported the hypothesised relations between perceived autonomy support and SDT's five types of motivations. Findings also showed that perceived autonomy support predicted job satisfaction directly and indirectly through the mediating roles of intrinsic motivation, identified regulation, introjected regulation and external regulation. Perceived autonomy support predicted work stress directly and indirectly through the mediating roles of external regulation and amotivation. Autonomy support also predicted illness symptoms via the mediating roles of intrinsic motivation, introjected regulation and amotivation. The current findings highlight how perceived organisational support for autonomy relates to motivational differences in a Chinese work context, and the potential relevance of autonomy support for employee well-being. PMID:25424389

  3. Role of edible film and coating additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Edible films and coatings have received increasing interest because films and coatings can carry a diversity of functional ingredients. Plasticizers, such as glycerol, acetylated monoglycerides, polyethylene glycol, and sucrose are often used to modify the mechanical properties of the film or coatin...

  4. Enhancement of the near-band-edge photoluminescence of ZnO nanowires: Important role of hydrogen incorporation versus plasmon resonances

    SciTech Connect

    Dev, A.; Richters, J. P.; Gutowski, J.; Voss, T.; Sartor, J.; Kalt, H.

    2011-03-28

    We investigated the photoluminescence properties of ZnO nanowires coated with Au, Ag, and Pt nanoparticles deposited by dc sputtering. A strong enhancement of the near-band-edge emission was observed in all metal-coated samples but also if the samples were treated with Ar plasma without any nanoparticle deposition. High-resolution photoluminescence spectroscopy revealed hydrogen-donor-bound-exciton emission in all samples indicating unintentional hydrogen incorporation. A shorter decay time of the near-band-edge emission was observed in all cases. The results indicate that unintentional hydrogen incorporation plays a dominant role when metal deposition is performed by sputtering.

  5. Life Roles, Values, and Careers. International Findings of the Work Importance Study. First Edition. The Jossey-Bass Social and Behavioral Science Series.

    ERIC Educational Resources Information Center

    Super, Donald E., Ed.; And Others

    This book answers fundamental questions about the nature of work in modern life based on the research from an innovative, cross-national project of the Work Importance Study (WIS). Part 1 presents the background for WIS. "Studies of the Meaning of Work" (Branimir Sverko, Vlasta Vizek-Vidovic) reviews the current state of understanding of the human…

  6. Pair importance measures in systems analysis

    SciTech Connect

    Youngblood, R.; Xue, D.; Cho, N.

    1986-01-01

    Importance measures in systems unreliability (or unavailability) analysis provide useful information in identifying components which are critical with regard to the availability or reliability of a system. Various importance measures known in the reliability literature are defined for a single component. This paper extends previous work to define importance measures for a pair of components of the system (accident sequence, core damage frequency, or health risks as appropriate), and illustrates the usefulness of these pairwise importance measures in nuclear power plants. The pairwise importance measures are immediately applicable to risk-based evaluation of the technical specifications; in addition, pairwise importances could play an important role in systems interaction studies by highlighting pairs of events between which a coupling would be significant if it existed.

  7. Expression of the Celsr/flamingo homologue, c-fmi1, in the early avian embryo indicates a conserved role in neural tube closure and additional roles in asymmetry and somitogenesis.

    PubMed

    Formstone, Caroline J; Mason, Ivor

    2005-02-01

    Flamingo is one of a core group of proteins that regulate planar cell polarity of epithelial structures within the Drosophila embryo while their vertebrate counterparts have been implicated in the coordination of convergent extension movements during gastrulation and in neural tube closure, suggesting that planar polarity mechanisms also function in these processes. Failure of neural tube closure is one of the most common human birth defects, and a murine flamingo (fmi) homologue, Celsr1/fmi-1, was identified as the defective gene in two mouse mutants exhibiting failure of closure 1 of the neural tube. This failure resulted in craniorachischisis in which the neural tube is open from the midbrain posteriorly. The avian embryo provides a tractable system to study neural tube closure. We have identified a chick Celsr1/fmi-1 orthologue, c-fmi1 and provide the first study of expression of an avian flamingo gene. We show that expression is highly dynamic in the early embryo and that c-fmi1 transcripts become enriched within the avian neural epithelium at the initiation of neural tube closure, suggesting a conserved function for Flamingo proteins in this process. Our data also suggest a role for c-fmi1 in myotome development. PMID:15614764

  8. The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule.

    PubMed

    Mégroz, Marianne; Kleifeld, Oded; Wright, Amy; Powell, David; Harrison, Paul; Adler, Ben; Harper, Marina; Boyce, John D

    2016-05-01

    The Gram-negative bacterium Pasteurella multocida is the causative agent of a number of economically important animal diseases, including avian fowl cholera. Numerous P. multocida virulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA-binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that a P. multocida hfq mutant produces significantly less hyaluronic acid capsule during all growth phases and displays reduced in vivo fitness. Transcriptional and proteomic analyses of the hfq mutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of the hfq mutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in the hfq mutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression of P. multocida genes, including the regulation of key P. multocida virulence factors, capsule, LPS, and filamentous hemagglutinin. PMID:26883595

  9. Campylobacter jejuni serine protease HtrA plays an important role in heat tolerance, oxygen resistance, host cell adhesion, invasion, and transmigration

    PubMed Central

    Lind, Judith; Backert, Steffen; Tegtmeyer, Nicole

    2015-01-01

    Campylobacter jejuni is an important pathogen of foodborne illness. Transmigration across the intestinal epithelial barrier and invasion are considered as primary reasons for tissue damage triggered by C. jejuni. Using knockout mutants, it was shown that the serine protease HtrA may be important for stress tolerance and physiology of C. jejuni. HtrA is also secreted in the extra­cellular environment, where it can cleave junctional host cell proteins such as E-cadherin. Aim of the present study was to establish a genetic complementation system in two C. jejuni strains in order to introduce the wild-type htrA gene in trans, test known htrA phenotypes, and provide the basis to perform further mutagenesis. We confirm that reexpression of the htrA wild-type gene in ΔhtrA mutants restored the following phenotypes: 1) C. jejuni growth at high temperature (44 °C), 2) growth under high oxygen stress conditions, 3) expression of proteolytically active HtrA oligomers, 4) secretion of HtrA into the supernatant, 5) cell attachment and invasion, and 6) transmigration across polarized epithelial cells. These results establish a genetic complementation system for htrA in C. jejuni, exclude polar effects in the ΔhtrA mutants, confirm important HtrA properties, and permit the discovery and dissection of new functions. PMID:25883795

  10. A DN-mda5 Transgenic Zebrafish 1 Model Demonstrates that Mda5 Plays an Important Role in Snakehead Rhabdovirus Resistance

    PubMed Central

    Gabor, KA; Charette, JR; Pietraszewski, MJ; Wingfield, DJ; Shim, JS; Millard, PJ; Kim, CH

    2015-01-01

    Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. PMID:25634485

  11. The role of FKBP5 in mood disorders: action of FKBP5 on steroid hormone receptors leads to questions about its evolutionary importance.

    PubMed

    O'Leary, John C; Zhang, Bo; Koren, John; Blair, Laura; Dickey, Chad A

    2013-12-01

    Research on the FKBP5 gene and FKBP51 protein has more than doubled since the discovery that polymorphisms in this gene could alter treatment outcomes and depressive behavior in humans. This coincided with other data suggesting that the stress hormone axis contributes to the development of numerous mental illnesses. As a result, FKBP51 now lies at the heart of the research of many stress related psychiatric disorders, which has led to advances in the understanding of this protein and its role in humans and in animal models. Specifically, FKBP5-/- mice and a naturally existing overexpression of FKBP5 in 3 genera of new world monkeys have helped understand the effects of FKBP5 in vivo. This review will highlight these finding as well as discuss the current evolutionary need for the FKBP5 gene. PMID:24040820

  12. Young adults' perceptions on life prospects and gender roles as important factors to influence health behaviour: a qualitative study from Karachi, Pakistan.

    PubMed

    Hasnain, Syed Farid-ul; Johansson, Eva; Mogren, Ingrid; Krantz, Gunilla

    2012-05-01

    The purpose of this qualitative study was to explore perceptions and expectations of young males and females, in Karachi, Pakistan, regarding their life prospects and gender roles, with resulting implications for health behaviour. The main theme emerging was "Young adults' prospects in life are hampered by psychosocial and gender equality constraints". Gender inequality and the low status of women in society were described as major obstacles to the overall development. Persistent withholding of information to the younger generation on sexual and reproductive health issues was perceived to increase exposure to health risks, particularly sexually transmitted infections (STIs). The present study reveals new discourses on equality among young adults, pointing towards an increasing, sound interaction between the sexes and aspirations for more gender equal relationships. Such views and awareness among the younger generation constitutes a strong force towards change of traditional norms, including reproductive health behaviour, and calls for policy change. PMID:22980235

  13. The role of FKBP5 in mood disorders: Action of FKBP5 on steroid hormone receptors leads to questions about its evolutionary importance

    PubMed Central

    O’Leary, John C.; Zhang, Bo; Koren, John; Blair, Laura; Dickey, Chad A.

    2014-01-01

    Research on the FKBP5 gene and FKBP51 protein has more than doubled since the discovery that polymorphisms in this gene could alter treatment outcomes and depressive behavior in humans. This coincided with other data suggesting that the stress hormone axis contributes to the development of numerous mental illnesses. As a result, FKBP51 now lies at the heart of the research of many stress related psychiatric disorders, which has led to advances in the understanding of this protein and its role in humans and in animal models. Specifically, FKBP5−/− mice and a naturally existing overexpression of FKBP5 in 3 genera of new world monkeys have helped understand the effects of FKBP5 in vivo. This review will highlight these finding as well as discuss the current evolutionary need for the FKBP5 gene. PMID:24040820

  14. Store-operated Ca2+ Entry-associated Regulatory factor (SARAF) Plays an Important Role in the Regulation of Arachidonate-regulated Ca2+ (ARC) Channels.

    PubMed

    Albarran, Letizia; Lopez, Jose J; Woodard, Geoffrey E; Salido, Gines M; Rosado, Juan A

    2016-03-25

    The store-operated Ca(2+)entry-associated regulatory factor (SARAF) has recently been identified as a STIM1 regulatory protein that facilitates slow Ca(2+)-dependent inactivation of store-operated Ca(2+)entry (SOCE). Both the store-operated channels and the store-independent arachidonate-regulated Ca(2+)(ARC) channels are regulated by STIM1. In the present study, we show that, in addition to its location in the endoplasmic reticulum, SARAF is constitutively expressed in the plasma membrane, where it can interact with plasma membrane (PM)-resident ARC forming subunits in the neuroblastoma cell line SH-SY5Y. Using siRNA-based and overexpression approaches we report that SARAF negatively regulates store-independent Ca(2+)entry via the ARC channels. Arachidonic acid (AA) increases the association of PM-resident SARAF with Orai1. Finally, our results indicate that SARAF modulates the ability of AA to promote cell survival in neuroblastoma cells. In addition to revealing new insight into the biology of ARC channels in neuroblastoma cells, these findings provide evidence for an unprecedented location of SARAF in the plasma membrane. PMID:26817842

  15. Interaction of myosin VI and its binding partner DOCK7 plays an important role in NGF-stimulated protrusion formation in PC12 cells.

    PubMed

    Sobczak, Magdalena; Chumak, Vira; Pomorski, Paweł; Wojtera, Emilia; Majewski, Łukasz; Nowak, Jolanta; Yamauchi, Junji; Rędowicz, Maria Jolanta

    2016-07-01

    DOCK7 (dedicator of cytokinesis 7) is a guanidine nucleotide exchange factor (GEF) for Rac1 GTPase that is involved in neuronal polarity and axon generation as well in Schwann cell differentiation and myelination. Recently, we identified DOCK7 as the binding partner of unconventional myosin VI (MVI) in neuronal-lineage PC12 cells and postulated that this interaction could be important in vivo [Majewski et al. (2012) Biochem Cell Biol., 90:565-574]. Herein, we found that MVI-DOCK7 interaction takes also place in other cell lines and demonstrated that MVI cargo domain via its RRL motif binds to DOCK7 C-terminal M2 and DHR2 domains. In MVI knockdown cells, lower Rac1 activity and a decrease of DOCK7 phosphorylation on Tyr1118 were observed, indicating that MVI could contribute to DOCK7 activity. MVI and DOCK7 co-localization was maintained during NGF-stimulated PC12 cell differentiation and observed also in the outgrowths. Also, during differentiation an increase in phosphorylation of DOCK7 as well as of its downstream effector JNK kinase was detected. Interestingly, overexpression of GFP-tagged MVI cargo domain (GFP-GT) impaired protrusion formation indicating that full length protein is important for this process. Moreover, a transient increase in Rac activity observed at 5min of NGF-stimulated differentiation of PC12 cells (overexpressing either GFP or GFP-MVI) was not detected in cells overexpressing the cargo domain. These data indicate that MVI-DOCK7 interaction could have functional implications in the protrusion outgrowth, and full length MVI seems to be important for delivery and maintenance of DOCK7 along the protrusions, and exerting its GEF activity. PMID:27018747

  16. Fluids in Convergent Margins: What do We Know about their Composition, Origin, Role in Diagenesis and Importance for Oceanic Chemical Fluxes?

    NASA Astrophysics Data System (ADS)

    Kastner, M.; Elderfield, H.; Martin, J. B.

    1991-05-01

    The nature and origin of fluids in convergent margins can be inferred from geochemical and isotopic studies of the venting and pore fluids, and is attempted here for the Barbados Ridge, Nankai Trough and the convergent margin off Peru. Venting and pore fluids with lower than seawater Cl- concentrations characterize all these margins. Fluids have two types of source: internal and external. The three most important internal sources are: (1) porosity reduction; (2) diagenetic and metamorphic dehydration; and (3) the breakdown of hydrous minerals. Gas hydrate formation and dissociation, authigenesis of hydrous minerals and the alteration of volcanic ash and/or the upper oceanic crust lead to a redistribution of the internal fluids and gases in vertical and lateral directions. The maximum amount of expelled water calculated can be ca. 7 m3 a-1 m-1, which is much less than the tens to more than 100 m3 a-1 m-1 of fluid expulsion which has been observed. The difference between these figures must be attributed to external fluid sources, mainly by transport of meteoric water enhanced by mixing with seawater. The most important diagenetic reactions which modify the fluid compositions, and concurrently the physical and even the thermal properties of the solids through which they flow are: (1) carbonate recrystallization, and more importantly precipitation; (2) bacterial and thermal degradation of organic matter; (3) formation and dissociation of gas hydrates; (4) dehydration and transformation of hydrous minerals, especially of clay minerals and opal-A; and (5) alteration, principally zeolitization and clay mineral formation, of volcanic ash and the upper oceanic crust.

  17. An important role of the moisture supply from the Kuroshio Current/Kuroshio Extension in the rapid development of an explosive cyclone

    NASA Astrophysics Data System (ADS)

    Hirata, H.; Kawamura, R.; Kato, M.; Shinoda, T.

    2014-12-01

    We investigated how the moisture supply from the Kuroshio Current/Kuroshio Extension affects the rapid intensification of an explosive cyclone using a couple atmosphere-ocean non-hydrostatic model, CReSS-NHOES. The Cloud-Resolving Storm Simulator (CReSS) and the Non-Hydrostatic Ocean model for the Earth Simulator (NHOES) have been developed by the Hydrospheric Atmospheric Research Center of Nagoya University and the Japan Agency for Marine-Earth Science and Technology, respectively. We performed a numerical simulation of an extratropical cyclone migrating along the southern periphery of the Kuroshio Current on January 14, 2013, that developed most rapidly in recent years in the vicinity of Japan. The evolutions of surface fronts related to the cyclone simulated by the CReSS-NHOES closely resemble Shapiro-Keyser model. In the lower troposphere, the cyclone's bent-back front and the associated frontal T-bone structure become evident with the cyclone development. Cold Conveyor Belt (CCB) is also well organized over the northern part of the cyclone. During its developing stage, since the CCB dominates just over the Kuroshio Current/Kuroshio Extension, a large amount of moisture is efficiently supplied from the warm current into the CCB. The vapor evaporated from the underlying warm current is transported into the bent-back front by the CCB and converges horizontally in the vicinity of the front. As a result, strong diabatic heating arises over the corresponding moisture convergence area in that vicinity, indicating that the abundant moisture due to the warm current plays a vital role in rapid development of the cyclone through latent heat release processes. Both processes of the moisture transport from the warm current into the cyclone system via the CCB and of the latent heat release around the bent-back front are also confirmed by trajectory analyses. The rapid SLP decrease of the cyclone center can in turn increase the moisture supply from the warm current through

  18. Proteomics of Fusarium oxysporum race 1 and race 4 reveals enzymes involved in carbohydrate metabolism and ion transport that might play important roles in banana Fusarium wilt.

    PubMed

    Sun, Yong; Yi, Xiaoping; Peng, Ming; Zeng, Huicai; Wang, Dan; Li, Bo; Tong, Zheng; Chang, Lili; Jin, Xiang; Wang, Xuchu

    2014-01-01

    Banana Fusarium wilt is a soil-spread fungal disease caused by Fusarium oxysporum. In China, the main virulence fungi in banana are F. oxysporum race 1 (F1, weak virulence) and race 4 (F4, strong virulence). To date, no proteomic analyses have compared the two races, but the difference in virulence between F1 and F4 might result from their differentially expressed proteins. Here we report the first comparative proteomics of F1 and F4 cultured under various conditions, and finally identify 99 protein species, which represent 59 unique proteins. These proteins are mainly involved in carbohydrate metabolism, post-translational modification, energy production, and inorganic ion transport. Bioinformatics analysis indicated that among the 46 proteins identified from F4 were several enzymes that might be important for virulence. Reverse transcription PCR analysis of the genes for 15 of the 56 proteins revealed that their transcriptional patterns were similar to their protein expression patterns. Taken together, these data suggest that proteins involved in carbohydrate metabolism and ion transport may be important in the pathogenesis of banana Fusarium wilt. Some enzymes such as catalase-peroxidase, galactosidase and chitinase might contribute to the strong virulence of F4. Overexpression or knockout of the genes for the F4-specific proteins will help us to further understand the molecular mechanism of Fusarium-induced banana wilt. PMID:25460190

  19. The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

    PubMed Central

    Papić, Dražen; Elbaz-Alon, Yael; Koerdt, Sophia Nina; Leopold, Karoline; Worm, Dennis; Jung, Martin

    2013-01-01

    A special group of mitochondrial outer membrane proteins spans the membrane once, exposing soluble domains to both sides of the membrane. These proteins are synthesized in the cytosol and then inserted into the membrane by an unknown mechanism. To identify proteins that are involved in the biogenesis of the single-span model protein Mim1, we performed a high-throughput screen in yeast. Two interesting candidates were the cytosolic cochaperone Djp1 and the mitochondrial import receptor Tom70. Our results indeed demonstrate a direct interaction of newly synthesized Mim1 molecules with Tom70. We further observed lower steady-state levels of Mim1 in mitochondria from djp1Δ and tom70 tom71Δ cells and massive mislocalization of overexpressed GFP-Mim1 to the endoplasmic reticulum in the absence of Djp1. Importantly, these phenotypes were observed specifically for the deletion of DJP1 and were not detected in mutant cells lacking any of the other cytosolic cochaperones of the Hsp40 family. Furthermore, the djp1Δ tom70Δ tom71Δ triple deletion resulted in a severe synthetic sick/lethal growth phenotype. Taking our results together, we identified Tom70 and Djp1 as crucial players in the biogenesis of Mim1. Moreover, the involvement of Djp1 provides a unique case of specificity between a cochaperone and its substrate protein. PMID:23959800

  20. Important role of fungal intracellular laccase for melanin synthesis: purification and characterization of an intracellular laccase from Lentinula edodes fruit bodies.

    PubMed

    Nagai, Masaru; Kawata, Maki; Watanabe, Hisayuki; Ogawa, Machiko; Saito, Kumiko; Takesawa, Toshikazu; Kanda, Katsuhiro; Sato, Toshitsugu

    2003-09-01

    A laccase (EC 1.10.3.2) was isolated from the fully browned gills of Lentinula edodes fruit bodies. The enzyme was purified to a homogeneous preparation using hydrophobic, cation-exchange and size-exclusion chromatography. SDS-PAGE analysis showed the purified laccase, Lcc 2, to be a monomeric protein of 58.0 kDa. The enzyme had an isoelectric point of around pH 6.9. The optimum pH for enzyme activity was around 3.0 against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt (ABTS), and it was most active at 40 degrees C and stable up to 50 degrees C. The enzyme contained 8.6 % carbohydrate and some copper atoms. The enzyme oxidized ABTS, p-phenylenediamine, pyrogallol, guaiacol, 2,6-dimethoxyphenol, catechol and ferulic acid, but not veratryl alcohol and tyrosine. Beta-(3,4-dihydroxyphenyl)alanine (L-DOPA), which was not oxidized by a laccase previously reported from the culture filtrate of L. edodes, was also oxidized by Lcc 2, and the oxidative product of L-dopa was identified as L-DOPA quinone by HPLC analysis. Lcc 2 was able to oxidize phenolic compounds extracted from fresh gills to brown-coloured products, suggesting a role for laccase in melanin synthesis in this strain. PMID:12949171